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In a first, 26-yr-old DMD patient in UP survives with stem cell therapy – Outlook India

By daniellenierenberg

In a first, 26-yr-old DMD patient in UP survives with stem cell therapy

Lucknow, Oct 22 (IANS) Duchenne Muscular Dystrophy (DMD) is a deadly genetic disorder, 99.9 per cent people suffering from which, die between the age of 13 to 23 years. However, in a first, a 26-year-old patient from Lucknow has survived DMD by regularly taking stem cells for the last five years.

Children, suffering from DMD, usually die of cardio-respiratory failure. But with the stem cell therapy, this patient has not lost muscle power in last five years and heart and lung muscles and the upper half of the body are working well.

Dr. B.S Rajput, the surgeon who is treating this patient, said, "DMD is a type of muscular dystrophy and being a genetic disorder, it is very difficult to treat. Autologous (from your own body) bone marrow cell transplant or stem cell therapy in such cases was started in Mumbai about 10 years back.

Dr Rajput, who was recently appointed as visiting professor at GSVM Medical College, Kanpur, said he has treated several hundred DMD patients and recently this combination protocol was published in the international Journal of Embryology and stem cell research.

The patient''s father is elated that his son has maintained well with this treatment and now has even started earning by working on computers.

According to Dr Rajput, this disease is endemic in eastern UP, especially Azamgarh, Jaunpur, Ballia and some of the adjoining districts of Bihar, and one out of every 3,500 male child, suffers from the disease.

Yet the disease is not given as much attention as it should be.

Dr Rajput, who is consultant bone cancer and stem cell transplant surgeon from Mumbai, said though patients in Uttar Pradesh and Bihar get financial support from the Chief Minister''s Relief Funds, the treatment of autologous bone marrow cell transplant is not included in the package list of Ayushman Bharat scheme, which deprives many from getting the treatment.

The doctor further informed that efforts are being made to establish the department of regenerative medicine in the medical college, where bone marrow cell transplant and stem cell therapy would be done even for other intractable problems like spinal cord injury, arthritis knee and motor neurone disease.

--IANS

amita/rtp

Disclaimer :- This story has not been edited by Outlook staff and is auto-generated from news agency feeds. Source: IANS

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Stem cells treatment gives hope in fighting Autism, blood disorders – OrissaPOST

By daniellenierenberg

Bhubaneswar: The advanced treatment of using stem cells for treating Autism and other neurological ailments have come as a ray of hope for the people living with some of these ailments. Medical experts working in the sector claim that the use of the technology improved the lives of many.

According to experts who practice stem cell therapy, the results have been overwhelming. Many of the patients have either been able to fight a deadly disease with the help of stem cells while many have been able to improve their quality of lives by using it. However, the technology is still not used widely in state hospitals.

Medical experts claim that stem cells could be used to treat neurological disorders like Autism, cerebral palsy, mental retardation, brain stroke, muscular dystrophy, spinal cord injury, head injury, cerebellar ataxia, dementia, motor neurone disease, multiple sclerosis while it has also been used to treat cancers like blood cancer with the help of bone marrow transplant when assisted by stem cell therapy.

However, treatment of Autism with stem cells is a new developing sector where visible changes are said to have been reported among children treated with this technology. However, the advanced technology which is now confined to only private sector is a bit expensive.

Autistic kids are usually treated with drugs for symptomatic relief, special education, occupational speech and behavioural therapies. In Autism, despite the best available medical and rehabilitative treatments satisfactory relief is still a far cry, said Dr Nandini Gokulchandran, Head Medical Services, NeuroGen Brain and Spine Institute, Mumbai.

Dr Gokulchandran claims that she has treated many cases of Autism in kids with stem cells which helped in overcoming their limited abilities. Under the treatment regime, an insertion procedure is undertaken followed by training to improve the skills and abilities of autistic kids.

Another neurologist, Dr Richa Bansod said that in India it has been reported that 1 in every 250 children have Autism and this number in increasing with better recognition and awareness of the condition. On the other hand, stem cells are now been used to fight deadly diseases.

Dr Joydeep Chakaborty, an oncologist and stem cell expert from HCG Cancer Hospital, Kolkata said, Stem cells and bone marrow transplants are now being used to cure blood cancer in many cases. It is also widely used to treat blood disorders like Thalassemia, Sickle Cell Anaemia and others.

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Cell Therapy Market outlook with industry review and forecasts – Technology Magazine

By daniellenierenberg

Cell therapy market size is estimated to grow significantly during the forecast period from 2019 to 2025. The cell therapy industry should witness substantial expansion over the forecast timeframe due to technological advancements coupled with increasing utilization of cell therapy along with gene therapy as treatment to several conditions.

Increasing funding from private organization as well as government to encourage cell therapy clinical trials, inclusion of varied cell types such as mesenchymal stem cells, skeletal muscle stem cells, lymphocytes, dendritic cells, hematopoietic stem cells (HSC) and pancreatic islet cells for cell therapy research will drive market size growth.

Bone marrow transplant or hematopoietic stem cell transplantation is most commonly performed cell therapy. Growing utilization of this therapy for treating conditions such as blood cancer and other hematologic conditions should drive industry growth. Potential application of cell therapy includes treatment for urinary problems, cancers, repairing spinal cord injuries, autoimmune disease, rebuilding damaged cartilage in joints, immune system improvement, neurological disorders and infectious disease. Such wide-ranging applications of cell therapy should drive business growth over the coming years.

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Increasing prevalence of chronic conditions, government assistance and numerous companies investing heavily in stem cell therapy research and development should stimulate industry growth. Proven effectiveness of cell therapy products coupled with rendering favorable guidelines pertaining to cell therapy manufacturing should positively impact industry growth. However, high cost and stringent regulations related to practicing of stem cell therapy will hamper industry growth to certain extent during the forecast period.

Based on therapy type, the industry is segmented into allogenic and autologous therapies. Autologous segment is anticipated to witness significant growth due to lower risk of fatal complications and graft failure resulting in high survival rate should drive segment growth. Moreover, significant investment in autologous cell therapy research by companies such as Vericel Corporation should positively impact growth.

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Applications of cell therapy include cardiovascular, ocular, musculoskeletal, gastrointestinal, oncology, neurological, dermatology, wounds and injuries, and others. Oncology segment is estimated to witness lucrative growth due to strong pipeline including Chimeric Antigen Receptor (CAR) T-cell therapy that has delivered promising results such as full recovery in end-stage patients suffering from acute lymphocytic leukemia during clinical trials.

Based on end-user, the industry is bifurcated into hospitals, diagnostic centers, clinics, research institutes, regenerative medicine centers and others. Stem cell is core component of regenerative medicine. Increasing research conducted by regenerative medicine researchers on variety of stem cell types such as multipotent adult stem cells (hematopoietic stem cells found in umbilical cord blood and mesenchymal stem cells [MSC] found in adipose tissue), along with pluripotent stem cells such as the bioengineered cells called induced pluripotent stem cells (iPSC) should drive segment growth.

North America cell therapy market will witness robust growth during the forecast period due to favorable regulatory framework to promote development of cellular therapy platform and presence of numerous companies engaged in cell therapy research. Rising awareness and growing healthcare expenditure should further propel industry growth.

Large patient population base suffering from chronic conditions along with development of healthcare infrastructure will drive Asia Pacific cell therapy market. Growing inclination towards advanced medicinal therapies will lead to growth of cell therapy market in the region.

Some notable industry players include, Vericel Corporation, Medipost, Cells for Cells, JCR Pharmaceuticals, Osiris Therapeutics, Kolon Tissuegene, NuVasive, Stemedica Cell Technologies, BioNTech IMFS, Anterogen, Pharmicell, Fibrocell Science, Novartis AG, Glaxosmithkline among others. Industry players are investing heavily in cell therapy research to develop innovative product and gain significant market share of lucrative market in future.

Browse more reports:

Coronary Stents Market: https://www.marketwatch.com/press-release/coronary-stents-market-detailed-analysis-of-current-industry-figures-with-forecasts-growth-by-2025-2019-10-18

Companion Animal Diagnostic Market: https://www.marketwatch.com/press-release/companion-animal-diagnostic-market-industry-growth-analysis-forecast-by-2025-2019-10-18

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Comparing of Axcella Health Inc. (AXLA) and Neuralstem Inc. (NASDAQ:CUR) – MS Wkly

By daniellenierenberg

Axcella Health Inc. (NASDAQ:AXLA) and Neuralstem Inc. (NASDAQ:CUR) compete against each other in the Biotechnology sector. We will compare them and contrast their analyst recommendations, institutional ownership, profitability, risk, dividends, earnings and valuation.

Valuation & Earnings

Table 1 shows gross revenue, earnings per share and valuation of the two companies.

Profitability

Table 2 provides the net margins, return on equity and return on assets of the two firms.

Analyst Recommendations

In next table is delivered Axcella Health Inc. and Neuralstem Inc.s ratings and recommendations.

Axcella Health Inc.s average price target is $22.5, while its potential upside is 330.21%.

Institutional and Insider Ownership

Roughly 0% of Axcella Health Inc. shares are owned by institutional investors while 4.9% of Neuralstem Inc. are owned by institutional investors. Comparatively, insiders own roughly 1% of Neuralstem Inc.s shares.

Performance

Here are the Weekly, Monthly, Quarterly, Half Yearly, Yearly and YTD Performance of both pretenders.

For the past year Axcella Health Inc. has stronger performance than Neuralstem Inc.

Summary

Axcella Health Inc. beats on 8 of the 10 factors Neuralstem Inc.

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The companys stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. It is developing products include NSI-189, a chemical entity, which is in Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical programs for the MCAO stroke, type 1 and 2 diabetes related neuropathy, irradiation-induced cognition, long-term potentiation enhancement, and angelman syndrome. The company is also developing NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease, as well as is in Phase I clinical trials for the treatment of chronic spinal cord injury and motor deficits due to ischemic stroke. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

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Reviewing Aldeyra Therapeutics Inc. (ALDX)’s and Neuralstem Inc. (NASDAQ:CUR)’s results – MS Wkly

By daniellenierenberg

Aldeyra Therapeutics Inc. (NASDAQ:ALDX) and Neuralstem Inc. (NASDAQ:CUR) compete against each other in the Biotechnology sector. We will compare them and contrast their profitability, institutional ownership, analyst recommendations, risk, dividends, earnings and valuation.

Valuation and Earnings

Table 1 demonstrates Aldeyra Therapeutics Inc. and Neuralstem Inc.s top-line revenue, earnings per share and valuation.

Profitability

Table 2 hightlights the net margins, return on assets and return on equity of the two companies.

Risk and Volatility

Aldeyra Therapeutics Inc.s 0.5 beta indicates that its volatility is 50.00% less volatile than that of S&P 500. Neuralstem Inc.s 94.00% more volatile than S&P 500 which is a result of the 1.94 beta.

Liquidity

The Current Ratio and a Quick Ratio of Aldeyra Therapeutics Inc. are 9.2 and 9.2. Competitively, Neuralstem Inc. has 3.8 and 3.8 for Current and Quick Ratio. Aldeyra Therapeutics Inc.s better ability to pay short and long-term obligations than Neuralstem Inc.

Institutional and Insider Ownership

Institutional investors held 69.9% of Aldeyra Therapeutics Inc. shares and 4.9% of Neuralstem Inc. shares. Aldeyra Therapeutics Inc.s share held by insiders are 2.2%. Insiders Competitively, held 1% of Neuralstem Inc. shares.

Performance

Here are the Weekly, Monthly, Quarterly, Half Yearly, Yearly and YTD Performance of both pretenders.

For the past year Aldeyra Therapeutics Inc. was less bearish than Neuralstem Inc.

Summary

On 9 of the 9 factors Aldeyra Therapeutics Inc. beats Neuralstem Inc.

Aldeyra Therapeutics, Inc., a biotechnology company, focuses on the development of products for inflammation, inborn errors of metabolism, and other diseases in the United States and internationally. It is developing ADX-102, a small molecule designed to trap and allow for the degradation of aldehydes, as well as ADX-103 and ADX-104 novel candidates for the treatment of noninfectious anterior uveitis, allergic conjunctivitis, dry eye syndrome, sjgren-larsson syndrome, and succinic semi-aldehyde dehydrogenase deficiency. The company was formerly known as Aldexa Therapeutics, Inc. and changed its name to Aldeyra Therapeutics, Inc. in March 2014. Aldeyra Therapeutics, Inc. was founded in 2004 and is headquartered in Lexington, Massachusetts.

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The companys stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. It is developing products include NSI-189, a chemical entity, which is in Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical programs for the MCAO stroke, type 1 and 2 diabetes related neuropathy, irradiation-induced cognition, long-term potentiation enhancement, and angelman syndrome. The company is also developing NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease, as well as is in Phase I clinical trials for the treatment of chronic spinal cord injury and motor deficits due to ischemic stroke. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

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BEYOND LOCAL: Expert recommends ‘path of cautious optimism’ about the future of stem cell treatment – TimminsToday

By daniellenierenberg

This article, written byKatharine Sedivy-Haley, University of British Columbia, originally appeared on The Conversation and is republished here with permission:

When I was applying to graduate school in 2012, it felt like stem cells were about to revolutionize medicine.

Stem cells have the ability to renew themselves, and mature into specialized cells like heart or brain cells. This allows them to multiply and repair damage.

If stem cell genes are edited to fix defects causing diseases like anemia or immune deficiency, healthy cells can theoretically be reintroduced into a patient, thereby eliminating or preventing a disease. If these stem cells are taken or made from the patient themselves, they are a perfect genetic match for that individual, which means their body will not reject the tissue transplant.

Because of this potential, I was excited that my PhD project at the University of British Columbia gave me the opportunity to work with stem cells.

However, stem cell hype has led some to pay thousands of dollars on advertised stem cell treatments that promise to cure ailments from arthritis to Parkinsons disease. These treatments often dont help and may harm patients.

Despite the potential for stem cells to improve medicine, there are many challenges as they move from lab to clinic. In general, stem cell treatment requires we have a good understanding of stem cell types and how they mature. We also need stem cell culturing methods that will reliably produce large quantities of pure cells. And we need to figure out the correct cell dose and deliver it to the right part of the body.

Embryonic, 'induced and pluripotent

Stem cells come in multiple types. Embryonic stem cells come from embryos which makes them controversial to obtain.

A newly discovered stem cell type is the induced pluripotent stem cell. These cells are created by collecting adult cells, such as skin cells, and reprogramming them by inserting control genes which activate or induce a state similar to embryonic stem cells. This embryo-like state of having the versatile potential to turn into any adult cell type, is called being pluripotent.

However, induced pluripotent and embryonic stem cells can form tumours. Induced pluripotent stem cells carry a particularly high risk of harmful mutation and cancer because of their genetic instability and changes introduced during reprogramming.

Genetic damage could be avoided by using younger tissues such as umbilical cord blood, avoiding tissues that might contain pre-existing mutations (like sun-damaged skin cells), and using better methods for reprogramming.

Stem cells used to test drugs

For now, safety concerns mean pluripotent cells have barely made it to the clinic, but they have been used to test drugs.

For drug research, it is valuable yet often difficult to get research samples with specific disease-causing mutations; for example, brain cells from people with amyotrophic lateral sclerosis (ALS).

Researchers can, however, take a skin cell sample from a patient, create an induced pluripotent stem-cell line with their mutation and then make neurons out of those stem cells. This provides a renewable source of cells affected by the disease.

This approach could also be used for personalized medicine, testing how a particular patient will respond to different drugs for conditions like heart disease.

Vision loss from fat stem cells

Stem cells can also be found in adults. While embryonic stem cells can turn into any cell in the body, aside from rare newly discovered exceptions, adult stem cells mostly turn into a subset of mature adult cells.

For example, hematopoietic stem cells in blood and bone marrow can turn into any blood cell and are widely used in treating certain cancers and blood disorders.

A major challenge with adult stem cells is getting the right kind of stem cell in useful quantities. This is particularly difficult with eye and nerve cells. Most research is done with accessible stem cell types, like stem cells from fat.

Fat stem cells are also used in stem cell clinics without proper oversight or safety testing. Three patients experienced severe vision loss after having these cells injected into their eyes. There is little evidence that fat stem cells can turn into retinal cells.

Clinical complications

Currently, stem cell based treatments are still mostly experimental, and while some results are encouraging, several clinical trials have failed.

In the brain, despite progress in developing treatment for genetic disorders and spinal cord injury, treatments for stroke have been unsuccessful. Results might depend on method of stem cell delivery, timing of treatment and age and health of the patient. Frustratingly, older and sicker tissues may be more resistant to treatment.

For eye conditions, a treatment using adult stem cells to treat corneal injuries has recently been approved. A treatment for macular degeneration using cells derived from induced pluripotent stem cells is in progress, though it had to be redesigned due to concerns about cancer-causing mutations.

A path of cautious optimism

While scientists have good reason to be interested in stem cells, miracle cures are not right around the corner. There are many questions about how to implement treatments to provide benefit safely.

In some cases, advertised stem cell treatments may not actually use stem cells. Recent research suggests mesenchymal stem cells, which are commonly isolated from fat, are really a mixture of cells. These cells have regenerative properties, but may or may not include actual stem cells. Calling something a stem cell treatment is great marketing, but without regulation patients dont know what theyre getting.

Members of the public (and grad students) are advised to moderate their excitement in favour of cautious optimism.

Katharine Sedivy-Haley, PhD Candidate in Microbiology and Immunology, University of British Columbia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Contrasting of ZIOPHARM Oncology Inc. (ZIOP) and Neuralstem Inc. (NASDAQ:CUR) – MS Wkly

By daniellenierenberg

ZIOPHARM Oncology Inc. (NASDAQ:ZIOP) and Neuralstem Inc. (NASDAQ:CUR) compete against each other in the Biotechnology sector. We will compare them and contrast their analyst recommendations, profitability, institutional ownership, risk, dividends, earnings and valuation.

Earnings and Valuation

In table 1 we can see ZIOPHARM Oncology Inc. and Neuralstem Inc.s top-line revenue, earnings per share and valuation.

Profitability

Table 2 has ZIOPHARM Oncology Inc. and Neuralstem Inc.s return on equity, return on assets and net margins.

Volatility and Risk

ZIOPHARM Oncology Inc. has a 2.55 beta, while its volatility is 155.00% which is more volatile than S&P 500. Neuralstem Inc. on the other hand, has 1.94 beta which makes it 94.00% more volatile compared to S&P 500.

Liquidity

ZIOPHARM Oncology Inc. has a Current Ratio of 8.9 and a Quick Ratio of 8.9. Competitively, Neuralstem Inc.s Current Ratio is 3.8 and has 3.8 Quick Ratio. ZIOPHARM Oncology Inc.s better ability to pay short and long-term obligations than Neuralstem Inc.

Analyst Recommendations

The Recommendations and Ratings for ZIOPHARM Oncology Inc. and Neuralstem Inc. are featured in the next table.

ZIOPHARM Oncology Inc. has an average price target of $6.5, and a 51.52% upside potential.

Institutional and Insider Ownership

Roughly 45.3% of ZIOPHARM Oncology Inc. shares are owned by institutional investors while 4.9% of Neuralstem Inc. are owned by institutional investors. ZIOPHARM Oncology Inc.s share owned by insiders are 0.5%. Competitively, Neuralstem Inc. has 1% of its share owned by insiders.

Performance

In this table we show the Weekly, Monthly, Quarterly, Half Yearly, Yearly and YTD Performance of both pretenders.

For the past year ZIOPHARM Oncology Inc. has 271.12% stronger performance while Neuralstem Inc. has -64.87% weaker performance.

Summary

ZIOPHARM Oncology Inc. beats Neuralstem Inc. on 10 of the 11 factors.

ZIOPHARM Oncology, Inc., a biotechnology company, focuses on acquiring, developing, and commercializing a portfolio of cancer therapies that address unmet medical needs through synthetic immuno-oncology. The company, through its collaboration agreement with Intrexon Corporation, holds certain rights to Intrexons synthetic immuno-oncology platform for use in the field of oncology, which includes a clinical stage product candidate, Ad-RTS-IL-12 evaluated for the treatment of metastatic melanoma, unresectable recurrent or metastatic breast cancer, and Grade III malignant glioma (GBM). Its synthetic immuno-oncology platform employs an inducible gene-delivery system that enables controlled in vivo expression of genes that produce therapeutic proteins to treat cancer. The company, under its license agreement with The University of Texas MD Anderson Cancer Center, along with Intrexon hold license to certain technologies relating to novel chimeric antigen receptor (CAR) T cell therapies, non-viral gene transfer systems, genetic modification and/or propagation of immune cells and other cellular therapy approaches, Natural Killer cells, and T cell receptors. It also has a research and development agreement with the National Cancer Institute utilizing Sleeping Beauty System to generate T cells receptors for the treatment of solid tumors. ZIOPHARM Oncology, Inc. is headquartered in Boston, Massachusetts.

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The companys stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. It is developing products include NSI-189, a chemical entity, which is in Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical programs for the MCAO stroke, type 1 and 2 diabetes related neuropathy, irradiation-induced cognition, long-term potentiation enhancement, and angelman syndrome. The company is also developing NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease, as well as is in Phase I clinical trials for the treatment of chronic spinal cord injury and motor deficits due to ischemic stroke. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

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Ridgefield woman, her mother write book about battle with MS – The Columbian

By daniellenierenberg

It hurt Margaret Godfrey to see daughter Rachel Carter in pain, so she painted.

And once the worst pain had passed, Carter needed a way to move forward, so she wrote.

In 2000, at age 24, Carter was diagnosed with multiple sclerosis, a disease where the immune system eats away at the lining of nerves and impairs or disables the brain and central nervous system.

Carter is now a married 43-year-old mother of three who lives in Ridgefield. But when she was diagnosed with MS, it marked a significant shift in her life. The woman who ran marathons, rode a motorcycle to high school and was once a deckhand on a small riverboat cruise ship to prove a point because she was told a woman couldnt hold that job, slowly morphed as her disease altered life.

It started with a fall on vacation during a run. Then falling on runs became more frequent. Gone went the marathons. In came the treadmill. Slowly, over the course of 12 years, the MS progressed and symptoms became debilitating. Running left completely. Neuropathic pain caused her to feel like she was sunburned in the morning, and by the afternoon or evening it felt like third degree burns. Carter left her job in sales in 2013.

I would always end up in tears in the bed, Carter said.

Carter has chronicled her battle with MS, and a stem cell treatment she credits with turning her prognosis around, in a new book called Enduring the Cure: My MS Journey to the Brink of Death and Back. Her mother helped her edit the book, and provided the books cover art. Adrienne van Der Valk also edited the book.

Through pain, Carter and her mother have created art. About five years ago, Carter underwent an experimental stem cell transplant in Seattle to help her rebuild her immune system. Carter lived in Seattle for about three months, while her parents watched two of her children, and the other child lived with an aunt.

As part of the procedure, Carters own stem cells were harvested and then reintroduced to her body after chemotherapy depleted most of her immune system. Its what she described as a rebooting of her whole immune system, in hopes that it would stop attacking her brain and spinal cord. Carter still has her previous brain damage, which impacts her memory and brain power; but so far, the stem cell transplant has improved her condition greatly, she said.

Carter has more energy she used to sometimes not be able to leave bed some days. She also can stand upright and walk easily she used to rely on a walker. And her pain is minimal now, the biggest improvement.

Carters family kept notes during her treatment, and Carter decided to use those, and the memories of her family, to help her write the book with van Der Valk.

Thinking was very fatiguing for Carter, since she still has the brain damage from MS. She could only work about one to two hours on the book at a time. She said writing was frustrating and hard in many ways. Parts of my brain are gone, Carter explained. She said it requires her about 10 times as much brain matter as the average person to process something simple.

Its so much pressure to have something you feel like you have to do, and then you cant do it. I had so little energy, Carter said. I cant explain very well because so many words dont come to me.

In spite of the challenges, Carter feels like sharing her experience will help others because, in life, we all have hard situations, she said.

Godfrey, a 70-year-old painter who lives in Blue River, Ore., found art in the familys experience. She drew inspiration from Gustav Klimt, an Austrian symbolist, who painted in the late 1800s and early 1900s, and created symbolic paintings of her daughter. Godfrey said art makes her an intellectual because of how she has to think about what shes painting. This time she was researching her own child.

Godfrey did a painting of Carter surrounded by old running shoes, a life she had to give up. She did a painting of Carter without her hair, which centered on Carters worries. She did a painting of Carter covered by a quilt with her three kids on it, what kept her going and allowed her to recover. She did a painting of Carter lying in a hospital bed, looking exhausted and resigned, which is the books cover. The final painting in the series, called The Journey Is Not Done, features Carter with hair, months after treatment. It has an unfinished mosaic because Carters journey isnt over.

Creating art is a very meditative thing, Godfrey said. Rather than getting wrapped up in emotions, once I start painting the world is me and paper. All the worries of life disappear. It was a way to enjoy that experience of just being able to throw out my expression, without getting too emotionally tangled up.

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Cellular Therapy in Oncology Market: Strategic Analysis to Understand the Competitive Outlook of the Industry, 2017 2025 – Online News Guru

By daniellenierenberg

Cellular therapy is also known as cytotherapy or cell therapy. Cellular therapy (CT) is the transplantation of cellular material into human body to repair or replace damaged tissue and damaged cells. Advancement in technology, development of innovative products, and growth in the number of research activities have helped in the discovery of several types of cells that are likely to be used in the treatment or therapy of various conditions and diseases. Several cells such as hematopoietic stem cells (HSC), mesenchymal stem cells, skeletal muscle stem cells, dendritic cells, pancreatic islet cells, and lymphocytes can be used in cellular therapy. HSC is extensively used in cellular therapy. Cellular therapy is used to treat various types of cancers, infectious diseases, autoimmune diseases, and urinary problems. The therapy also helps patients rebuild damaged cartilage in joints, improve a weakened immune system, and repair spinal cord injuries. Moreover, it also helps treat neurological disorders. Cellular cancer therapy has various approaches as the cell can be designed to stimulate the patients immune system (T cells or natural killer cells) to kill cancer cells, or to replace most of the patients immune system to enhance their immune response to cancer cells, or to directly find and kill the cancer cells.

The global cellular therapy in oncology market has been classified based on cancer type and geography. In terms of cancer type, the market has been categorized into blood cancer, prostate cancer, pancreatic cancer, brain cancer, and other cancer. The blood cancer segment accounts for a major share of cellular therapy in oncology market. Increasing prevalence of prostate cancer is expected propel the segment in the near future. According to WHO statistics, 8.2 million people die each year due to cancer which estimates about 13% of all death worldwide. There are more than 100 types of cancers that require unique diagnoses and therapies. This increases the demand for cellular therapy in oncology in near future.

Geographically, the cellular therapy in oncology market has been segmented into five major regions: North America, Europe, Latin America, Asia Pacific, and Middle East & Africa. In terms of revenue, North America dominates the cellular therapy in oncology market followed by Europe. The market in Asia Pacific and Latin America is developing. This trend is expected to continue during the forecast period. Availability of large patient pool, expansion of the health care industry, and rise in government investment to improve the health care industry are anticipated to propel the market in these regions. The cellular therapy in oncology market in countries such as Brazil, China, and India are projected to expand at substantial growth rate during the forecast period due to rise in awareness among the population about the usage of cellular therapy to treat various types of cancers and rapid innovations in cellular therapy.

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Increasing prevalence of various cancers, affordability of cellular therapy in cancer drugs, high adoption in developed markets, and development of innovative drugs are other factors driving the cellular therapy in oncology market. High competition among existing players, high risks of failure, severity and complications involved in cellular therapy due to misdiagnosis, and lack of awareness among the rural population in underdeveloped and developing economies are likely to inhibit the market.

Major players operating in the cellular therapy in oncology market include Alkem Laboratories Limited, Amgen, Inc., Bayer AG, Sanofi, Bristol-Myers Squibb, Boehringer Ingelheim GmbH, F. Hoffmann-La Roche Ltd, Cipla, Inc., Merck & Co., Inc., Eli Lilly and Company, GlaxoSmithKline Plc., Johnson & Johnson Services, Inc., Novartis AG, Pfizer, Inc., and Teva Pharmaceutical Industries Ltd.

The report offers a comprehensive evaluation of the market. It does so via in-depth qualitative insights, historical data, and verifiable projections about market size. The projections featured in the report have been derived using proven research methodologies and assumptions. By doing so, the research report serves as a repository of analysis and information for every facet of the market, including but not limited to: Regional markets, technology, types, and applications.

The study is a source of reliable data on: Market segments and sub-segments Market trends and dynamics Supply and demand Market size Current trends/opportunities/challenges Competitive landscape Technological breakthroughs Value chain and stakeholder analysis

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The regional analysis covers: North America (U.S. and Canada) Latin America (Mexico, Brazil, Peru, Chile, and others) Western Europe (Germany, U.K., France, Spain, Italy, Nordic countries, Belgium, Netherlands, and Luxembourg) Eastern Europe (Poland and Russia) Asia Pacific (China, India, Japan, ASEAN, Australia, and New Zealand) Middle East and Africa (GCC, Southern Africa, and North Africa)

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

Highlights of the report: A complete backdrop analysis, which includes an assessment of the parent market Important changes in market dynamics Market segmentation up to the second or third level Historical, current, and projected size of the market from the standpoint of both value and volume Reporting and evaluation of recent industry developments Market shares and strategies of key players Emerging niche segments and regional markets An objective assessment of the trajectory of the market Recommendations to companies for strengthening their foothold in the market

Note:Although care has been taken to maintain the highest levels of accuracy in TMRs reports, recent market/vendor-specific changes may take time to reflect in the analysis.

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Vericel Corporation (VCEL) and BioTime Inc. (:) Contrasting side by side – MS Wkly

By daniellenierenberg

Both Vericel Corporation (NASDAQ:VCEL) and BioTime Inc. (:) compete on a level playing field in the Biotechnology industry. We will evaluate their performance with regards to analyst recommendations, profitability, risk, institutional ownership, dividends, earnings and valuation.

Earnings and Valuation

We can see in table 1 the earnings per share, gross revenue and valuation of Vericel Corporation and BioTime Inc.

Profitability

Table 2 shows us the return on equity, return on assets and net margins of both companies.

Volatility and Risk

Vericel Corporation has a 2.72 beta, while its volatility is 172.00% which is more volatile than S&P 500. BioTime Inc. has a 2.81 beta and it is 181.00% more volatile than S&P 500.

Liquidity

Vericel Corporations Current Ratio is 8.5 while its Quick Ratio is 8.2. On the competitive side is, BioTime Inc. which has a 3.5 Current Ratio and a 3.5 Quick Ratio. Vericel Corporation is better positioned to pay off short and long-term obligations compared to BioTime Inc.

Analyst Recommendations

The Recommendations and Ratings for Vericel Corporation and BioTime Inc. are featured in the next table.

Vericel Corporations upside potential currently stands at 48.79% and an $21.5 average price target.

Institutional and Insider Ownership

The shares of both Vericel Corporation and BioTime Inc. are owned by institutional investors at 89% and 43.7% respectively. About 0.5% of Vericel Corporations share are held by insiders. Insiders Comparatively, held 3.9% of BioTime Inc. shares.

Performance

In this table we provide the Weekly, Monthly, Quarterly, Half Yearly, Yearly and YTD Performance of both pretenders.

For the past year Vericel Corporations stock price has smaller growth than BioTime Inc.

Vericel Corporation, a commercial-stage biopharmaceutical company, researches, develops, manufactures, markets, and sells patient-specific expanded cellular therapies for use in the treatment of patients with severe diseases and conditions. It markets three autologous cell therapy products, including Carticel and MACI, which are used for the treatment of cartilage defects in the knee; and Epicel, a permanent skin replacement that is used for the treatment of patients with deep-dermal or full-thickness burns comprising greater than or equal to 30 percent of total body surface area in the United States. The company also develops ixmyelocel-T, which is in Phase IIb clinical trial, a patient-specific multicellular therapy for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy. The company was formerly known as Aastrom Biosciences, Inc. Vericel Corporation was founded in 1989 and is headquartered in Cambridge, Massachusetts.

BioTime, Inc., a clinical-stage biotechnology company, focuses on developing and commercializing products addressing degenerative diseases based on pluripotent stem cells and HyStem cell/drug delivery platform technologies. Its product candidates include Renevia, a facial aesthetics product that is in pivotal clinical trial for the treatment of HIV related facial lipoatrophy; OpRegen, which is in Phase I/IIa clinical trial for the treatment of the dry form of age-related macular degeneration; HyStem-BDNF, a preclinical development program for the delivery of recombinant human brain-derived neurotrophic factor (BDNF) directly into the stroke cavity of patients for aiding in tissue repair and functional recovery; and ReGlyde that is in preclinical development as a device for viscosupplementation and a combination product for drug delivery in osteoarthritis. The company also develops AST-OPC1, a therapy derived from pluripotent stem cells that is in a Phase I/IIa clinical trial for spinal cord injuries; AST-VAC1, a patient-specific cancer immunotherapy that is in Phase II clinical trial for acute myeloid leukemia; and AST-VAC2, a non-patient specific cancer immunotherapy, which is in Phase I/IIa clinical trial to treat non-small cell lung cancer. In addition, it offers liquid biopsy tests for diagnosis of cancer; bone grafting products to treat orthopedic disorders; and mobile health software products. Further, it markets GeneCards, a human gene database; LifeMap Discovery, a database of embryonic development, stem cell research, and regenerative medicine; MalaCards, a human disease database; VarElect, an application for prioritizing gene variants; and GeneAnalytics, a novel gene set analysis tool. Additionally, the company develops and markets Hextend, a blood plasma volume expander used for the treatment of hypovolemia. BioTime, Inc. was founded in 1990 and is based in Alameda, California.

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Postdoctoral Fellow, School of Biomedical Sciences job with THE UNIVERSITY OF HONG KONG | 182916 – Times Higher Education (THE)

By daniellenierenberg

Work type: Full-timeDepartment: School of Biomedical Sciences (22600)Categories: Academic-related Staff

Applications are invited for appointment as Post-doctoral Fellow in the School of Biomedical Sciences (Ref.: 498889), to commence as soon as possible for three years, with the possibility of renewal.

Applicants should have a Ph.D. degree in Molecular Biology, Cell Biology, Neurobiology or a related discipline. Preference will be given to those with experience in human neural stem cell culture and vivo spinal injury models. Applicants should also have a good command of both written and spoken English. The appointee will study the therapeutic potential of genetically modified human neural stem cells in rodent spinal cord injury models. Please visit http://www.sbms.hku.hk/staff/martin-chi-hang-cheung or contact Dr. Martin Cheung at mcheung9@hku.hk for further information. Applicants who have responded to the previous advertisement (Ref.: 494003) need not re-apply.

A highly competitive salary commensurate with qualifications and experience will be offered, in addition to annual leave and medical benefits

The University only accepts online application for the above post. Applicants should apply online and upload an up-to-date C.V.Review of applications will start on October 23, 2019 and continue untilJanuary 31, 2020, or until the post is filled, whichever is earlier.

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Comparing of Kura Oncology Inc. (KURA) and Neuralstem Inc. (NASDAQ:CUR) – MS Wkly

By daniellenierenberg

Kura Oncology Inc. (NASDAQ:KURA) and Neuralstem Inc. (NASDAQ:CUR) compete against each other in the Biotechnology sector. We will contrast them and contrast their profitability, institutional ownership, analyst recommendations, risk, dividends, earnings and valuation.

Earnings and Valuation

Table 1 highlights Kura Oncology Inc. and Neuralstem Inc.s gross revenue, earnings per share and valuation.

Profitability

Table 2 demonstrates the return on assets, return on equity and net margins of Kura Oncology Inc. and Neuralstem Inc.

Risk & Volatility

A beta of 2.5 shows that Kura Oncology Inc. is 150.00% more volatile than Standard & Poors 500. In other hand, Neuralstem Inc. has beta of 1.94 which is 94.00% more volatile than Standard & Poors 500.

Liquidity

The current Quick Ratio of Kura Oncology Inc. is 13.8 while its Current Ratio is 13.8. Meanwhile, Neuralstem Inc. has a Current Ratio of 3.8 while its Quick Ratio is 3.8. Kura Oncology Inc. is better positioned to pay off its short-term and long-term debts than Neuralstem Inc.

Analyst Ratings

The following table shown below contains the ratings and recommendations for Kura Oncology Inc. and Neuralstem Inc.

Kura Oncology Inc.s consensus price target is $22, while its potential upside is 58.96%.

Institutional & Insider Ownership

Kura Oncology Inc. and Neuralstem Inc. has shares owned by institutional investors as follows: 70.8% and 4.9%. Insiders owned roughly 0.8% of Kura Oncology Inc.s shares. Insiders Comparatively, owned 1% of Neuralstem Inc. shares.

Performance

In this table we show the Weekly, Monthly, Quarterly, Half Yearly, Yearly and YTD Performance of both pretenders.

For the past year Kura Oncology Inc. had bullish trend while Neuralstem Inc. had bearish trend.

Summary

Kura Oncology Inc. beats Neuralstem Inc. on 10 of the 11 factors.

Kura Oncology, Inc., a clinical stage biopharmaceutical company, develops medicines for the treatment of cancers. Its pipeline consists of small molecule product candidates that target cancer. The companys lead product candidate is Tipifarnib, an oral farnesyl transferase inhibitor that is in Phase II clinical trials for the treatment of solid tumors, peripheral T-cell lymphomas, lower risk myelodysplastic syndromes, and chronic myelomonocytic leukemia. It also develops KO-947, a small molecule inhibitor of extracellular signal related kinase used for the treatment for patients with tumors that have mutations in, or other dysregulation of, the mitogen-activated protein kinase; and KO-539, a small molecule inhibitor of the menin-mixed lineage leukemia. The company was founded in 2014 and is headquartered in La Jolla, California.

Neuralstem, Inc., a clinical stage biopharmaceutical company, focuses on the research and development of nervous system therapies based on its proprietary human neuronal stem cells and small molecule compounds. The companys stem cell based technology enables the isolation and expansion of human neural stem cells from various areas of the developing human brain and spinal cord enabling the generation of physiologically relevant human neurons of various types. It is developing products include NSI-189, a chemical entity, which is in Phase II clinical trial for the treatment of major depressive disorder, as well as is in preclinical programs for the MCAO stroke, type 1 and 2 diabetes related neuropathy, irradiation-induced cognition, long-term potentiation enhancement, and angelman syndrome. The company is also developing NSI-566, which has completed Phase II clinical trial for treating amyotrophic lateral sclerosis disease, as well as is in Phase I clinical trials for the treatment of chronic spinal cord injury and motor deficits due to ischemic stroke. Neuralstem, Inc. was founded in 1996 and is headquartered in Germantown, Maryland.

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What is being done to treat MS? – Telegraph.co.uk

By Dr. Matthew Watson

Considered untreatable until the early 1990s, multiple sclerosis (MS) has benefited in recent decades from huge progress in developing treatments for people with relapsing MS, the most common form of the condition at the point of diagnosis. But there are many people living with the progressive forms of MS who face increasing disability and still have very few, if any, treatment options.

Thats why the MS Society is now focusing its attention on finding effective treatments for everyone with MS. And it has a clear plan to get there.

To stop MS, people will need to be treated with a combination of drugs, explains the charitys director of research, Dr Susan Kohlhaas. This might include one drug that acts on the immune system, another that prompts brain stem cells to repair damage to myelin, the fatty substance protecting nerve fibres, and a treatment that increases the resilience of brain and nerve cells to help prevent damage occurring in the first place.

Were now at a point where were beginning to understand the molecular mechanisms that cause myelin damage and promote repair exactly what we need to stop MS, she says. Were also in the middle of a promising trial of a common statin, which we think may be able to protect nerves. The Stop MS Appeal is about making sure we have a coordinated approach to developing these treatments and can do it as quickly and efficiently as possible.

In early 2020, the MS Society plans to launch a world-leading clinical trials platform to test multiple treatments for MS at the same time. The aim is to set up a large trial in which several drugs can be tested concurrently on different groups of patients the first time this will ever have been done in neurodegenerative disease.

It will be a much more efficient process than having separate trials and means participants will have a much higher chance of receiving an active treatment that may work, rather than a placebo. Regular reviews will ensure that promising drugs can go straight through to late-stage clinical trials, while ineffective drugs are dropped and replaced by others.

This means desperately needed new treatments could reach people living with progressive MS much faster, says Dr Kohlhaas. We now have around 40 researchers actively working on the programme and theres a real sense of momentum and excitement about its potential.

The MS Society Tissue Bank is a repository of brain and spinal-cord tissue donated by people with MS after their death to help researchers understand more about the condition. The charity has recently invested 1.5million to fund new developments at the facility including a digital brain bank of high-definition pictures of brain tissue that will allow researchers around the world easier access to the resource.

The MS Society also funds research facilities around the UK and the UK MS Register, which enables people to record information about the progress of their condition every six months. An important research tool and source of data, it can also help identify patients for new trials.

Something Im really proud of is that we involve people with MS in the decision-making about research, says Dr Kohlhaas. They sit on our panels and committees to decide what to fund, and they have a strong voice. Im confident this approach has absolutely changed our way of working and ensured we really focus on what people with MS want.

Our vision is that, by 2025, well have treatments in late-stage clinical trials that can be taken through into practice quite quickly, and that well soon have the ability to start treating people with combinations of treatments that not only slow the progress of MS but can actually stop it.

This article is brought to you by the MS Society and Telegraph Spark. The MS Society believes that with investment, MS can be stopped. Scientists can see a future in which no one with the condition need worry about it getting worse. But action is needed now.

Donate today and help the MS Society raise 100million to find treatments for everyone. Visit mssociety.org.uk/stop-ms-now

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Stem Cells Market : Insights Into the Competitive Scenario of the Market – Online News Guru

By Dr. Matthew Watson

In theglobal stem cells marketa sizeable proportion of companies are trying to garner investments from organizations based overseas. This is one of the strategies leveraged by them to grow their market share. Further, they are also forging partnerships with pharmaceutical organizations to up revenues.

In addition, companies in the global stem cells market are pouring money into expansion through multidisciplinary and multi-sector collaboration for large scale production of high quality pluripotent and differentiated cells. The market, at present, is characterized by a diverse product portfolio, which is expected to up competition, and eventually growth in the market.

Some of the key players operating in the global stem cells market are STEMCELL Technologies Inc., Astellas Pharma Inc., Cellular Engineering Technologies Inc., BioTime Inc., Takara Bio Inc., U.S. Stem Cell, Inc., BrainStorm Cell Therapeutics Inc., Cytori Therapeutics, Inc., Osiris Therapeutics, Inc., and Caladrius Biosciences, Inc.

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As per a report by Transparency Market Research, the global market for stem cells is expected to register a healthy CAGR of 13.8% during the period from 2017 to 2025 to become worth US$270.5 bn by 2025.

Depending upon the type of products, the global stem cell market can be divided into adult stem cells, human embryonic stem cells, induced pluripotent stem cells, etc. Of them, the segment of adult stem cells accounts for a leading share in the market. This is because of their ability to generate trillions of specialized cells which may lower the risks of rejection and repair tissue damage.

Depending upon geography, the key segments of the global stem cells market are North America, Latin America, Europe, Asia Pacific, and the Middle East and Africa. At present, North America dominates the market because of the substantial investments in the field, impressive economic growth, rising instances of target chronic diseases, and technological progress. As per the TMR report, the market in North America will likely retain its dominant share in the near future to become worth US$167.33 bn by 2025.

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Investments in Research Drives Market

Constant thrust on research to broaden the utility scope of associated products is at the forefront of driving growth in the global stem cells market. Such research projects have generated various possibilities of different clinical applications of these cells, to usher in new treatments for diseases.Since cellular therapies are considered the next major step in transforming healthcare, companies are expanding their cellular therapy portfolio to include a range of ailments such as Parkinsons disease, type 1 diabetes, spinal cord injury, Alzheimers disease, etc.

The growing prevalence of chronic diseases and increasing investments of pharmaceutical and biopharmaceutical companies in stem cell research are the key driving factors for the stem cells therapeutics market. The growing number of stem cell donors, improved stem cell banking facilities, and increasing research and development are other crucial factors serving to propel the market, explains the lead analyst of the report.

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Caroline Wyatt: The fight to reverse damage caused by MS – BBC News

By Dr. Matthew Watson

Image caption Caroline Wyatt visited Prof Robin Franklin to find out more about a drug that might help stop the progression of MS

"I don't like to think of the future. It's such a big question mark. I just keep living in the present."

Karine Mather was diagnosed with MS when she was 27, although she noticed the first symptoms much earlier.

It started off as a mental-health issue with anxiety and depression, she remembers. Later, she noticed she was starting to limp when she walked longer distances.

Karine began using a walker to help with her balance and stamina, and then a scooter when she could no longer walk very far.

"I got to the stage where the wheelchair became quite liberating, and gave me back a sense of freedom again. Now I rely on the power-chair full-time because I can't stand by myself any more."

Now Karine and her wife, Sarah, have had to give up their full-time jobs.

Karine was forced to stop working as a customer service adviser at a bank because she could no longer fulfil the physical demands of work and Sarah gave up working as a data analyst so she could take care of Karine.

Now 34, Karine retains the use of just one hand, and suffers pain, stiffness and spasticity in her body that has got worse as the disease has progressed.

"It feels like a fist clenching all the time. And I have days when my mind is cloudy and I miss out words and sentences."

Both remain upbeat but the financial, as well as the emotional, impact of MS has been huge.

Karine's MS is the type known as "primary progressive", or PPMS, which meant that for the first years after diagnosis, no disease-modifying treatment was available.

One new drug - Ocrevus, or ocrelizumab - was recently licensed for early PPMS in the UK but came too late to help Karine.

Now the MS Society is launching an ambitious "Stop MS" appeal, aiming to raise 100m to fund research over the next decade into treatments that can stop the progression of disability in MS.

Since being diagnosed with MS in 2015, after many years of symptoms, I've been looking for anything that might help slow or even stop the progression of my MS, which affects the nerves in my brain and spinal cord.

I last wrote about my MS after travelling to Mexico for an autologous stem cell transplant (aHSCT) in 2017.

Sadly, despite initial improvements, I'm now back to where I was before: slowly but surely getting worse.

The only improvements that have endured are the lifting of some of the crushing brain fog I had before HSCT and less hesitation in my speech.

For both, I am eternally grateful, as they mean I can continue to work at the BBC, in the job I love.

However, I have no idea how long this reprieve will last.

The fatigue that had long been my worst symptom is now back with a vengeance, so that staying awake throughout a busy working day remains a challenge.

That MS fatigue did lift for a few months, and it felt miraculous. I awoke every day refreshed. But then it returned, and I awake after eight full hours fast asleep feeling as if I haven't been to bed at all.

The ageing process - including menopause - has almost certainly been a factor in the worsening of some symptoms.

Ageing cells repair less well, and with my faulty immune system apparently determined to keep stripping away the myelin sheath that should protect my nerves, I'm less able now to repair the damage than I was when the disease first began to affect me in around 1992.

Since 2016, I've had to walk using a stick to aid my balance. It is sparkly-topped; an effort to make the accoutrements of disability just a little more cheery.

Dizziness is now a constant companion. It rarely goes away, making car travel or even buses a nightmare. Just turning my head too fast can make me stagger or fall over.

And for the past year or two, my right foot has begun to drag along the ground thanks to foot drop, meaning that I trip more often because I can't fully raise it.

I am always grateful to the strangers who kindly stop to help me up from the uneven pavement when I do fall.

Perhaps most worrying for me is that my right hand no longer works as it used to, catching on the computer keyboard as my outer fingers drag lazily along the keys, sullenly refusing my brain's command to lift.

In the mornings, both my hands and my feet are numb and frozen, then painfully full of pins and needles before warming up enough to be usable a few hours later.

When I wake, I wonder how long it might be until these hands and feet barely function at all, and quickly push that unwelcome thought away.

I'm well aware how very lucky I am that the progression of my MS has been relatively slow - at least until recently. I've learned how better to conserve energy for the things that really matter, though I still chafe at how little I manage to achieve.

Having enough energy to cook a meal from scratch on a day off is a cause for rejoicing. I'm still learning how to save up enough energy for family and friends, and not use up all of my much-depleted ration for work or research.

I have had to face the fact that I have now probably gone from the relapsing-remitting phase of MS (for which a dozen or so treatments exist) into the secondary progressive phase, for which there is currently no treatment licensed in the UK to stop the relentless progression that will affect so many of the 100,000 or more of us living with MS here.

But that may be about to change.

Anna Williams, professor of regenerative neurology at the University of Edinburgh, is looking at how the brain responds to MS damage and how the fatty myelin sheath under attack in MS can be restored more efficiently.

"We have to look at ways to stop the nerves dying," she says. "We want to be able to try to limit that either by keeping the nerves alive, or keeping them working better."

Repurposing existing drugs to help with remyelination should prove the quickest route to therapies for progressive forms of MS, because creating and licensing new ones is a much lengthier and more expensive process.

Prof Williams still sees patients at the Anne Rowling Clinic of Regenerative Neurology in Edinburgh, named in memory of the Harry Potter author J K Rowling's mother, who had MS. (The author this year donated 15m for research at the unit.)

"At the moment, with PPMS or SPMS, we can always give relief for pain or stiffness but we won't change the course of the disease.

"So for those patients, to slow or stop or reverse the disease can only be done with more research, and money is critical for research."

The biggest trial yet in the UK for patients with secondary progressive MS is the MS STAT2 trial, conducted by Prof Jeremy Chataway for the UCL Queen Square Institute of Neurology in London.

The trial is still recruiting at 30 centres across the UK to look at whether simvastatin, a drug used to treat high cholesterol, can slow or stop disability progression. If so, it has the potential to become one of the first disease-modifying therapies for people with secondary progressive MS.

And perhaps most encouraging of all, Prof Robin Franklin and his team at the Wellcome-MRC Cambridge Stem Cell Institute recently published research suggesting a common diabetes drug - metformin - could hold the key to stopping disease progression in MS.

Costing just a few pence per tablet, metformin appears to have an ability to restore cells to a younger, healthier state and encourage myelin regrowth.

The next question is whether it works in people as well as it does in the lab.

Prof Franklin says: "This is a drug that's well tolerated and widely available. There is every reason to believe that the effects that we have seen - which have been so spectacular - will translate into humans.

"This is the great frontier of MS therapy. We're good at stopping the inflammation in MS. What we're not so good at doing is repairing the damage. All this work has given us some real hope that this medicine will reverse the damage done by MS."

I certainly feel rather more hopeful than I did.

I've changed as much about my lifestyle as I can - prioritising sleep, eating healthily, largely giving up alcohol, doing yoga and stretching every day, and cutting back on stress, be that reporting from war zones or attending too many BBC meetings.

But I'm all too aware that time is against me as my ageing brain and body struggle to repair the damage done in their lengthy continuing battle with my own immune system.

My hope now is that these trials will show good enough results in the next few years for at least one or two of the drugs to be rapidly approved for MS so they can help people like Karine and me before it's too late.

I ask Karine what she makes of the current research.

She is suitably succinct.

"I'm sitting here with just the one limb working and I'm thinking - quicker, please."

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Lineage Cell Therapeutics Announces Issuance of U.S …

By Dr. Matthew Watson

CARLSBAD, Calif.--(BUSINESS WIRE)--

Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, announced today that the United States Patent and Trademark Office (USPTO) has issued U.S. Patent No. 10,286,009, entitled Pluripotent stem cell-derived oligodendrocyte progenitor cells for the treatment of spinal cord injury covering methods for utilizing pluripotent stem cell-derived oligodendrocyte progenitor cells (OPCs) for the treatment of spinal cord injury (SCI). The claimed methods involve injecting OPCs derived from a pluripotent human stem cell line into the SCI site and covers both human embryonic and induced pluripotent stem cell-derived OPCs. The issued patent has a term that expires no earlier than 2036.

The issuance of this patent is an important milestone for the Company because the allowed claims provide valuable, long term protection for novel treatments employing off-the-shelf OPC1 cells designed to improve recovery outcomes following severe spinal cord injury, stated Brian M. Culley, Chief Executive Officer of Lineage. We believe we have one of the largest cell therapy intellectual property portfolios in the biotech industry and will continue to grow and defend our position as a leader in this exciting space.

OPC1 cells are produced by directing the developmental lineage of pluripotent cell lines to generate a proprietary and consistent population of oligodendritic cells. These cells are administered to the patient in an effort to confer post-injury regeneration, which is intended to provide greater motor recovery compared to the current standard of care. With encouraging data already generated from a 25-patient Phase I safety trial, the current focus for the OPC1 program is to introduce commercially-viable improvements to the manufacturing process and to initiate a comparative study later in 2020.

About OPC1

OPC1 is currently being tested in Phase I/IIa clinical trial known as SCiStar, for the treatment of acute spinal cord injuries. OPCs are naturally-occurring precursors to the cells which provide electrical insulation for nerve axons in the form of a myelin sheath. SCI occurs when the spinal cord is subjected to a severe crush or contusion injury and typically results in severe functional impairment, including limb paralysis, aberrant pain signaling, and loss of bladder control and other body functions. The clinical development of the OPC1 program has been partially funded by a $14.3 million grant from the California Institute for Regenerative Medicine. OPC1 has received Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of acute SCI and has been granted Orphan Drug designation from the U.S. Food and Drug Administration (FDA).

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its proprietary cell-based therapy platform and associated development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally-differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed either to replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical assets include (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase I/IIa development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase I/IIa development for the treatment of acute spinal cord injuries; and (iii) VAC2, an allogeneic cancer immunotherapy of antigen-presenting dendritic cells currently in Phase I development for the treatment of non-small cell lung cancer. For more information, please visit http://www.lineagecell.com or follow the Company on Twitter @LineageCell.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as believe, may, will, estimate, continue, anticipate, design, intend, expect, could, plan, potential, predict, seek, should, would, contemplate, project, target, tend to, or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to changes in Lineages manufacturing process and the timing of future studies. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineages actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including risks and uncertainties inherent in Lineages business and other risks described in Lineages filings with the Securities and Exchange Commission (SEC). Lineages forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading Risk Factors in Lineages periodic reports filed with the SEC, including Lineages Annual Report on Form 10-K filed with the SEC on March 14, 2019 and its other reports, which are available from the SECs website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

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Stem cells: The secret to change | Science News for Students

By Dr. Matthew Watson

Inside your body, red blood cells are constantly on the move. They deliver oxygen to every tissue in every part of your body. These blood cells also cart away waste. So their work is crucial to your survival. But all that squeezing through tiny vessels is tough on red blood cells. Thats why they last only about four months.

Where do their replacements come from? Stem cells.

These are a very special family of cells. When most other cells divide, the daughter cells look and act exactly like their parents. For example, a skin cell cant make anything but another skin cell. The same is true for cells in the intestine or liver.

Not stem cells. Stem cells can become many different types. That is how an embryo grows from a single fertilized egg into a fetus with trillions of specialized cells. They need to specialize to make up tissues that function very differently, including those in the brain, skin, muscle and other organs. Later in life, stem cells also can replace worn-out or damaged cells including red blood cells.

The remarkable abilities of stem cells make them very exciting to scientists. One day, experts hope to use stem cells to repair or replace many different kinds of tissues, whether injured in accidents or damaged by diseases. Such stem cell therapy would allow the body to heal itself. Scientists have found a way to put specialized cells to work repairing damage, too. Together, these cell-based therapies might one day make permanent disabilities a thing of the past.

One unusual type of stem cell offers special promise for such therapeutic uses. For the recent development of this cell type, Shinya Yamanaka shared the 2012 Nobel Prize in medicine.

Meet the family

Blood stem cells live inside your bones, in what is called marrow. There, they divide over and over. Some of the new cells remain stem cells. Others form red blood cells. Still others morph into any of the five types of white blood cells that will fight infections. Although blood stem cells can become any one of these specialized blood cells, they cannot become muscle, nerve or other types of cells. They are too specialized to do that.

Another type of stem cell is more generalized. These can mature into any type of cell in the body. Such stem cells are called pluripotent (PLU ree PO tint). The word means having many possibilities. And its not hard to understand why these cells have captured the imaginations of many scientists.

Until recently, all pluripotent cells came from embryos. Thats why scientists called them embryonic stem cells. After an egg is fertilized, it divides in two. These two cells split again, to become four cells, and so on. In the first few days of this embryos development, each of its cells is identical to all the others. Yet each cell has the potential to develop into any specialized cell type.

When the human embryo reaches three to five days old, its cells start to realize their potential. They specialize. Some will develop into muscle cells or bone cells. Others will form lung cells or maybe the cells lining the stomach. Once cells specialize, their many possibilities suddenly become limited.

By birth, almost all of a babys cells will have specialized. Each cell type will have its own distinctive shape and function. For example, muscle cells will be long and able to contract, or shorten. Red blood cells will be small and plate-shaped, so they can slip through blood vessels with ease.

Hidden among all of these specialized cells are pockets of adult stem cells. (Yes, even newborns have adult stem cells.) Unlike embryonic stem cells, adult stem cells cannot transform into any and every cell type. However, adult stem cells can replace several different types of specialized cells as they wear out. One type of adult stem cell is found in your marrow, making new blood cells. More types are found in other tissues, including the brain, heart and gut.

Among naturally occurring stem cells, the embryonic type is the most useful. Adult stem cells just arent as flexible. The adult type also is relatively rare and can be difficult to separate from the tissues in which it is found. Although more versatile, embryonic stem cells are both difficult to obtain and controversial. Thats because harvesting them requires destroying an embryo.

Fortunately, recent discoveries in stem cell research now offer scientists a third and potentially better option.

The search for answers

In 2006, Shinya Yamanaka discovered that specialized cells like those in skin could be converted back into stem cells. Working at Kyoto University in Japan, this doctor and scientist induced or persuaded mature cells to become stem cells. He did this by inserting a specific set of genes into the cells. After several weeks, the cells behaved just like embryonic cells. His new type of stem cells are called induced pluripotent stem cells, or iP stem cells (and sometimes iPS cells).

Yamanakas discovery represented a huge leap forward. The iP stem cells offer several advantages over both embryonic and adult stem cells. First, iP stem cells are able to become any cell type, just as embryonic stem cells can. Second, they can be made from any starting cell type. That means they are easy to obtain. Third, in the future, doctors would be able to treat patients with stem cells created from their own tissues. Such cells would perfectly match the others, genetically. That means the patients immune system (including all of its white blood cells) would not attack the introduced cells. (The body often mounts a life-threatening attack against transplanted organs that come from other people because they dont offer such a perfect match. To the body, they seem foreign and a potentially dangerous invader.)

Scientists the world over learned of the technique developed by Yamanaka (who now works at the Gladstone Institutes which is affiliated with the University of California, San Francisco). Many of these researchers adopted Yamanakas procedure to create their own induced pluripotent stem cells. For the first time, researchers had a tool that could allow them to make stem cells from people with rare genetic diseases. This helps scientists learn what makes certain cell types die. Experts can also expose small batches of these diseased cells to different medicines. This allows them to test literally thousands of drugs to find out which works best.

And in the future, many experts hope induced stem cells will be used to replace adult stem cells and the cells of tissues that are damaged or dying.

Therapies take patients and patience

Among those experts is Anne Cherry, a graduate student at Harvard University. Cherry is using induced stem cells to learn more about a very rare genetic disease called Pearson syndrome. A syndrome is a group of symptoms that occur together. One symptom of Pearson syndrome is that stem cells in bone marrow cannot make normal red blood cells. This condition typically leads to an early death.

Cherry has begun to study why these stem cells fail.

She started by taking skin cells from a girl with the disease. She placed the cells in a test tube and added genes to turn them into stem cells. Over several weeks, the cells began to make proteins for which the inserted genes had provided instructions. Proteins do most of the work inside cells. These proteins turned off the genes that made the cells act like skin cells. Before long, the proteins turned on the genes to make these cells behave like embryonic stem cells.

After about three months, Cherry had a big batch of the new induced stem cells. Those cells now live in Petri dishes in her lab, where they are kept at body temperature (37 Celsius, or 98.6 Fahrenheit). The scientist is now trying to coax the induced stem cells into becoming blood cells. After that, Cherry wants to find out how Pearson syndrome kills them.

Meanwhile, the patient who donated the skin cells remains unable to make blood cells on her own. So doctors must give her regular transfusions of blood from a donor. Though life-saving, transfusions come with risks, particularly for someone with a serious disease.

Cherry hopes to one day turn the girls induced stem cells into healthy new blood stem cells and then return them to the girls body. Doing so could eliminate the need for further transfusions. And since the cells would be the girls own, there would be no risk of her immune system reacting to them as though they were foreign.

Sight for sore eyes

At University of Nebraska Medical Center in Omaha, Iqbal Ahmad is working on using stem cells to restore sight to the blind. A neuroscientist someone who studies the brain and nervous system Ahmad has been focusing on people who lost sight when nerve cells in the eyes retina died from a disease called glaucoma (glaw KOH muh).

Located inside the back of the eye, the retina converts incoming light into electrical signals that are then sent to the brain. Ahmad is studying how to replace dead retina cells with new ones formed from induced pluripotent stem cells.

The neuroscientist starts by removing adult stem cells from the cornea, or the clear tissue that covers the front of the eye. These stem cells normally replace cells lost through the wear and tear of blinking. They cannot become nerve cells at least not on their own. Ahmad, however, can transform these cells into iP stem cells. Then, with prodding, he turns them into nerve cells.

To make the transformation, Ahmad places the cornea cells on one side of a Petri dish. He then places embryonic stem cells on the other side. A meshlike membrane separates the two types of cells so they cant mix. But even though they cant touch, they do communicate.

Cells constantly send out chemical signals to which other cells respond. When the embryonic stem cells speak, the eye cells listen. Their chemical messages persuade the eye cells to turn off the genes that tell them to be cornea cells. Over time, the eye cells become stem cells that can give rise to different types of cells, including nerve cells.

When Ahmads team implanted the nerve cells into the eyes of laboratory mice and rats, they migrated to the retina. There, they began replacing the nerve cells that had died from glaucoma. One day, the same procedure may restore vision to people who have lost their sight.

Another approach

In using a bodys own cells to repair injury or to treat disease, stem cells arent always the answer. Although stem cells offer tremendous advances in regenerating lost tissue, some medical treatments may work better without them. Thats thanks to the chemical communication going on between all cells all of the time. In some situations, highly specialized cells can act as a conductor, directing other cells to change their tune.

In 2008, while working at the University of Cambridge in England, veterinary neurologist Nick Jeffery began a project that used cells taken from the back of the nose. But Jeffery and his team were not out to create stem cells. Instead, the scientists used those nasal cells to repair damaged connections in the spinal cord.

The spinal cord is basically a rope of nerve cells that ferry signals to and from the brain and other parts of the body. Injuring the spinal cord can lead to paralysis, or the loss of sensation and the inability to move muscles.

Like Ahmad, some researchers are using stem cells to replace damaged nerve cells. But Jeffery, now at Iowa State University in Ames, doesnt think such techniques are always necessary to aid recovery from spinal injuries. Stem cell transplantation, points out Jefferys colleague, neuroscientist Robin Franklin, is to replace a missing cell type. In a spinal injury, the nerve cells arent missing. Theyre just cut off.

Nerve cells contain long, wirelike projections called axons that relay signals to the next cell. When the spine is injured, these axons can become severed, or cut. Damaging an axon is like snipping a wire the signal stops flowing. So the Cambridge scientists set out to see if they could restore those signals.

Jeffery and his fellow scientists work with dogs that have experienced spinal injuries. Such problems are common in some breeds, including dachshunds. The team first surgically removed cells from the dogs sinuses or the hollow spaces in the skull behind the nose. These are not stem cells. These particular cells instead encourage nerve cells in the nose to grow new axons. These cells help the pooches maintain their healthy sense of smell.

The scientists grew these sinus cells in the lab until they had reproduced to large numbers. Then the researchers injected the cells into the spinal cords of two out of every three doggy patients. Each treated dog received an injection of its own cells. The other dogs got an injection of only the liquid broth used to feed the growing cells.

Over several months, the dogs owners repeatedly brought their pets back to the lab for testing on a treadmill. This allowed the scientists to evaluate how well the animals coordinated their front and hind feet while walking. Dogs that had received the nasal cells steadily improved over time. Dogs that received only the liquid did not.

This treatment did not result in a perfect cure. Nerve cells did reconnect several portions of the spinal cord. But nerve cells that once linked to the brain remained disconnected. Still, these dog data indicate that nasal cells can aid in recovering from a spinal cord injury.

Such new developments in cellular research suggest that even more remarkable medical advancements may be just a few years away. Yamanaka, Cherry, Ahmad, Jeffery, Franklin and many other scientists are steadily unlocking secrets to cellular change. And while you cant teach an old dog new tricks, scientists are finding out that the same just isnt true of cells anymore.

cornea The clear covering over the front of the eye.

embryo A vertebrate, or animal with a backbone, in its early stages of development.

gene A section of DNA that carries the genetic instructions for making a protein. Proteins do most of the work in cells.

glaucoma An eye disease that damages nerve cells carrying signals to the brain.

immune cell White blood cell that helps protect the body against germs.

molecule A collection of atoms.

neuron (or nerve cell) The basic working unit of the nervous system. These cells relay nerve signals.

neuroscientist A researcher who studies neurons and the nervous system.

paralysis Loss of feeling in some part of the body and an inability to move that part.

retina The light-sensitive lining at the back of the eye. It converts light into electrical impulses that relay information to the brain.

sinus An opening in the bone of the skull connected to the nostrils.

spinal cord The ropelike collection of neurons that connect the brain with nerves throughout the body.

tissue A large collection of related, similar cells that together work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues. And brain tissue will be very different from bone or heart tissue.

transfusion The process of transferring blood into one person that had been collected from another.

Word Find (click here to enlarge puzzle for printing)

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Prognosis of Spinal Cord Injuries | SpinalCord.com

By Dr. Matthew Watson

The prognosis for spinal cord injuries varies depending on the severity of the injury. There is always hope of recovering some function with spinal cord injuries. The completeness and location of the injury will determine the prognosis.

There are two levels of completeness in spinal cord injuries which impact the outlook:

Spinal cord injuries in which the patient has not experienced paralysis have the greatest chance of recovery. However, those patients who do experience paralysis still have a remarkable chance that is improving with research every day. The sooner treatments are implemented to strengthen muscles below the level of the spinal cord injury, the better the prognosis.

The first year of recovery is the hardest as the patient is just beginning to adjust to his or her condition. The use of physical and occupational therapy during this time is the key to recovery. The extent of the function fully returning is typically seen in the first two years after the initial injury.

Treatment options vary with each spinal cord injury, but typically include:

Mental health is a huge part of recovery for the spinal cord injury patient. Anxiety and depression are common in spinal cord injury patients. These patients will go through good days, and not so good days.

There may be days where the patient wants to give up completely on treatments, and will wonder if it is all worth it. Keeping up with the mental health of the spinal cord injury patient is incredibly important for the overall recovery. Mental health has been proven to directly relate to physical health.

Having a good support system is incredibly important to the overall outlook of a spinal cord injury patient. Spinal cord injury patients will need both physical and emotional support.

Caregivers should continually provide patients with:

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Hematopoietic Stem Cells: What Diseases Can these Stem …

By Dr. Matthew Watson

Hematopoietic stem cells (HSCs) are defined as stem cells that have a preference for becoming cells of the blood and immune system, such as white bloodcells, red bloodcells, and platelets. Found in the peripheral blood and bone marrow,hematopoietic stem cells are also present in plentiful supply within the umbilical cord blood of newborn babies.

For the past thirty years, cord blood has been used within transplant medicine, including for the treatment of leukemia and other blood diseases. For most conditions in which a bone marrow or peripheral blood stem cell transplant is an option, a cord blood transplant is a potential alternative.

In this article:

Hematopoietic stem cells(HSCs) are thestem cellsthat repopulate the blood and immune system within humans, via a process known ashaematopoiesis. For this reason, hematopoietic stem cell transplantation, better known as HSCT, can be a promising treatment approach for a wide range of conditions.

The use of human cord blood cells dates back as early as 1974, when it was first proposed that stem cell and progenitor cells were present in human cord blood.By 1983, the use of cord blood as an alternative to bone marrow had been proposed. Five years later in 1988, the first successful cord blood transplant to restore a patients blood and immune system cells took place in France.

In addition to a long history of use within transplant medicine, human cord blood cells are playing a growing role within regenerative medicine. Cord blood stem cells have been induced to develop into neural cells, suggesting that they may represent a potential treatment for neurological conditions, such as Alzheimers, Parkinsons, spinal cord injury, dementia, and related conditions.

Human cord blood cells can also develop into blood vessels, making them promising for the repair of tissues following stroke, coronary heart disease, rheumatic heart disease, congestive heart failure, and congenital heart conditions.

What Are the Benefits of Banking #CordBlood? The main benefit to banking cord blood is it allows parents to preserve stem cells for future medical use. Many parts of the body do not regenerate, so they are at risk of failing https://t.co/3oc4Ai4qef pic.twitter.com/kYy9Ds64ad

BioInformant (@StemCellMarket) July 23, 2018

It is also interesting to consider the common disease categories treatable with cord blood transplant, as shown in the table below.

There are more than 80 medical conditions for which transplantation of hematopoietic stem cells (including cord blood transplant) is a standard treatment option. Most of these therapies require allogeneic transplants, where the patient must use a genetically-matched cord blood donor. The only exceptions to this are patients who are transplanted for solid tumors or acquired anemias. In these situations, the patient may receive an autologous transplant.

Comprehensive lists of conditions treatable with hematopoietic stem cells are available here and here.

In addition, there is a range of disease categories for which cord blood transplant could represent a viable treatment method in the future. For these conditions, there are still unknown criteria that need to be determined before the cord blood stem cell transplant can become commonplace, such as patient criteria for optimal treatment effectiveness, optimum stem cell quantity for use in transplant, and preferred method of stem cell delivery into the patient, as shown below.

Download this infographic now and reference it later.

What do you think of the future of hematopoietic stem cell transplant? Share your thoughts in the comments below.

Hematopoietic Stem Cells: What Diseases Can these Stem Cells Treat?

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Neural Stem Cells – Stemcell Technologies

By Dr. Matthew Watson

The Central Nervous System

The mature mammalian central nervous system (CNS) is composed of three major differentiated cell types: neurons, astrocytes and oligodendrocytes. Neurons transmit information through action potentials and neurotransmitters to other neurons, muscle cells or gland cells. Astrocytes and oligodendrocytes, collectively called glial cells, play important roles of their own, in addition to providing a critical support role for optimal neuronal functioning and survival. During mammalian embryogenesis, CNS development begins with the induction of the neuroectoderm, which forms the neural plate and then folds to give rise to the neural tube. Within these neural structures there exists a complex and heterogeneous population of neuroepithelial progenitor cells (NEPs), the earliest neural stem cell type to form.1,2 As CNS development proceeds, NEPs give rise to temporally and spatially distinct neural stem/progenitor populations. During the early stage of neural development, NEPs undergo symmetric divisions to expand neural stem cell (NSC) pools. In the later stage of neural development, NSCs switch to asymmetric division cycles and give rise to lineage-restricted progenitors. Intermediate neuronal progenitor cells are formed first, and these subsequently differentiate to generate to neurons. Following this neurogenic phase, NSCs undergo asymmetric divisions to produce glial-restricted progenitors, which generate astrocytes and oligodendrocytes. The later stage of CNS development involves a period of axonal pruning and neuronal apoptosis, which fine tunes the circuitry of the CNS. A previously long-held dogma maintained that neurogenesis in the adult mammalian CNS was complete, rendering it incapable of mitotic divisions to generate new neurons, and therefore lacking in the ability to repair damaged tissue caused by diseases (e.g. Parkinsons disease, multiple sclerosis) or injuries (e.g. spinal cord and brain ischemic injuries). However, there is now strong evidence that multipotent NSCs do exist, albeit only in specialized microenvironments, in the mature mammalian CNS. This discovery has fuelled a new era of research into understanding the tremendous potential that these cells hold for treatment of CNS diseases and injuries.

Neurobiologists routinely use various terms interchangeably to describe undifferentiated cells of the CNS. The most commonly used terms are stem cell, precursor cell and progenitor cell. The inappropriate use of these terms to identify undifferentiated cells in the CNS has led to confusion and misunderstandings in the field of NSC and neural progenitor cell research. However, these different types of undifferentiated cells in the CNS technically possess different characteristics and fates. For clarity, the terminology used here is:

Neural Stem Cell (NSCs): Multipotent cells which are able to self-renew and proliferate without limit, to produce progeny cells which terminally differentiate into neurons, astrocytes and oligodendrocytes. The non-stem cell progeny of NSCs are referred to as neural progenitor cells.

Neural Progenitor Cell: Neural progenitor cells have the capacity to proliferate and differentiate into more than one cell type. Neural progenitor cells can therefore be unipotent, bipotent or multipotent. A distinguishing feature of a neural progenitor cell is that, unlike a stem cell, it has a limited proliferative ability and does not exhibit self-renewal.

Neural Precursor Cells (NPCs): As used here, this refers to a mixed population of cells consisting of all undifferentiated progeny of neural stem cells, therefore including both neural progenitor cells and neural stem cells. The term neural precursor cells is commonly used to collectively describe the mixed population of NSCs and neural progenitor cells derived from embryonic stem cells and induced pluripotent stem cells.

Prior to 1992, numerous reports demonstrated evidence of neurogenesis and limited in vitro proliferation of neural progenitor cells isolated from embryonic tissue in the presence of growth factors.3-5 While several sub-populations of neural progenitor cells had been identified in the adult CNS, researchers were unable to demonstrate convincingly the characteristic features of a stem cell, namely self-renewal, extended proliferative capacity and retention of multi-lineage potential. In vivo studies supported the notion that proliferation occurred early in life, whereas the adultCNS was mitotically inactive, and unable to generate new cells following injury. Notable exceptions included several studies in the 1960s that clearly identified a region of the adult brain that exhibited proliferation (the forebrain subependyma)6 but this was believed to be species-specific and was not thought to exist in all mammals. In the early 1990s, cells that responded to specific growth factors and exhibited stem cell features in vitro were isolated from the embryonic and adult CNS.7-8 With these studies, Reynolds and Weiss demonstrated that a rare population of cells in the adult CNS exhibited the defining characteristics of a stem cell: self-renewal, capacity to produce a large number of progeny and multilineage potential. The location of stem cells in the adult brain was later identified to be within the striatum,9 and researchers began to show that cells isolated from this region, and the dorsolateral region of the lateral ventricle of the adult brain, were capable of differentiating into both neurons and glia.10

During mammalian CNS development, neural precursor cells arising from the neural tube produce pools of multipotent and more restricted neural progenitor cells, which then proliferate, migrate and further differentiate into neurons and glial cells. During embryogenesis, neural precursor cells are derived from the neuroectoderm and can first be detected during neural plate and neural tube formation. As the embryo develops, neural stem cells can be identified in nearly all regions of the embryonic mouse, rat and human CNS, including the septum, cortex, thalamus, ventral mesencephalon and spinal cord. NSCs isolated from these regions have a distinct spatial identity and differentiation potential. In contrast to the developing nervous system, where NSCs are fairly ubiquitous, cells with neural stem cell characteristics are localized primarily to two key regions of the mature CNS: the subventricular zone (SVZ), lining the lateral ventricles of the forebrain, and the subgranular layer of thedentate gyrus of the hippocampal formation (described later).11 In the adult mouse brain, the SVZ contains a heterogeneous population of proliferating cells. However, it is believed that the type B cells (activated GFAP+/PAX6+ astrocytes or astrogliallike NSCs) are the cells that exhibit stem cell properties, and these cells may be derived directly from radial glial cells, the predominant neural precursor population in the early developing brain. NPCs in this niche are relatively quiescent under normal physiological conditions, but can be induced to proliferate and to repopulate the SVZ following irradiation.10 SVZ NSCs maintain neurogenesis throughout adult life through the production of fast-dividing transit amplifying progenitors (TAPs or C cells), which then differentiate and give rise to neuroblasts. TAPs and neuroblasts migrate through the rostral migratory stream (RMS) and further differentiate into new interneurons in the olfactory bulb. This ongoing neurogenesis, which is supported by the NSCs in the SVZ, is essential for maintenance of the olfactory system, providing a source of new neurons for the olfactory bulb of rodents and the association cortex of non-human primates.12 Although the RMS in the adult human brain has been elusive, a similar migration of neuroblasts through the RMS has also been observed.13 Neurogenesis also persists in the subgranular zone of the hippocampus, a region important for learning and memory, where it leads to the production of new granule cells. Lineage tracing studies have mapped the neural progenitor cells to the dorsal region of the hippocampus, in a collapsed ventricle within the dentate gyrus.10 Studies have demonstrated that neurogenic cells from the subgranular layer may have a more limited proliferative potential than the SVZ NSCs and are more likely to be progenitor cells than true stem cells.14 Recent evidence also suggests that neurogenesis plays a different role in the hippocampus than in the olfactory bulb. Whereas the SVZ NSCs play a maintenance role, it is thought that hippocampal neurogenesis serves to increase the number of new neurons and contributes to hippocampal growth throughout adult life.12 Neural progenitor cells have also been identified in the spinal cord central canal ventricular zone and pial boundary15-16, and it is possible that additional regional progenitor populations will be identified in the future.

In vitro methodologies designed to isolate, expand and functionally characterize NSC populations have revolutionized our understanding of neural stem cell biology, and increased our knowledge of the genetic and epigenetic regulation of NSCs.17 Over the past several decades, a number of culture systems have been developed that attempt to recapitulate the distinct in vivo developmental stages of the nervous system, enabling theisolation and expansion of different NPC populations at different stages of development. Here, we outline the commonly used culture systems for generating NPCs from pluripotent stem cells (PSCs), and for isolating and expanding NSCs from the early embryonic, postnatal and adult CNS.

Neural induction and differentiation of pluripotent stem cells: Early NPCs can be derived from mouse and human PSCs, which include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), using appropriate neural induction conditions at the first stage of differentiation. While these neural differentiation protocols vary widely, a prominent feature in popular embryoid body-based protocols is the generation of neural rosettes, morphologically identifiable structures containing NPCs, which are believed to represent the neural tube. The NPCs present in the neural rosette structures are then isolated, and can be propagated to allow NPC expansion, while maintaining the potential to generate neurons and glial cells. More recently, studies have shown that neural induction of PSCs can also be achieved in a monolayer culture system, wherein human ESCs and iPSCs are plated onto a defined matrix, and exposed to inductive factors.18 A combination of specific cytokines or small molecules, believed to mimic the developmental cues for spatiotemporal patterning in the developing brain during embryogenesis, can be added to cultures at the neural induction stage to promote regionalization of NPCs. These patterned NPCs can then be differentiated into mature cell types with phenotypes representative of different regions of the brain.19-24 New protocols have been developed to generate cerebral organoids from PSC-derived neural progenitor cells. Cerebral organoids recapitulate features of human brain development, including the formation of discrete brain regions featuring characteristic laminar cellular organization.25

Neurosphere culture: The neurosphere culture system has been widely used since its development as a method to identify NSCs.26-29 A specific region of the CNS is microdissected, mechanically or enzymatically dissociated, and plated in adefined serum-free medium in the presence of a mitogenic factor, such as epidermal growth factor (EGF) and/or basic fibroblast growth factor (bFGF). In the neurosphere culture system, NSCs, as well as neural progenitor cells, begin to proliferate in response to these mitogens, forming small clusters of cells after 2 - 3 days. The clusters continue to grow in size, and by day 3 - 5, the majority of clusters detach from the culture surface and begin to grow in suspension. By approximately day seven, depending on the cell source, the cell clusters, called neurospheres, typically measure 100 - 200 m in diameter and are composed of approximately 10,000 - 100,000 cells. At this point, the neurospheres should be passaged to prevent the cell clusters from growing too large, which can lead to necrosis as a result of a lack of oxygen and nutrient exchange at the neurosphere center. To passage the cultures, neurospheres are individually, or as a population, mechanically or enzymatically dissociated into a single cell suspension and replated under the same conditions as the primary culture. NSCs and neural progenitor cells again begin to proliferate to form new cell clusters that are ready to be passaged approximately 5 - 7 days later. By repeating the above procedures for multiple passages, NSCs present in the culture will self-renew and produce a large number of progeny, resulting in a relatively consistent increase in total cell number over time. Neurospheres derived from embryonic mouse CNS tissue treated in this manner can be passaged for up to 10 weeks with no loss in their proliferative ability, resulting in a greater than 100- fold increase in total cell number. NSCs and neural progenitors can be induced to differentiate by removing the mitogens and plating either intact neurospheres or dissociated cells on an adhesive substrate, in the presence of a low serum-containing medium. After several days, virtually all of the NSCs and progeny will differentiate into the three main neural cell types found in the CNS: neurons, astrocytes and oligodendrocytes. While the culture medium, growth factor requirements and culture protocols may vary, the neurosphere culture system has been successfully used to isolate NSCs and progenitors from different regions of the embryonic and adult CNS of many species including mouse, rat and human.

Adherent monolayer culture: Alternatively, cells obtained from CNS tissues can be cultured as adherent cultures in a defined, serum-free medium supplemented with EGF and/or bFGF, in the presence of a substrate such as poly-L-ornithine, laminin, or fibronectin. When plated under these conditions, the neural stem and progenitor cells will attach to the substrate-coated cultureware, as opposed to each other, forming an adherent monolayer of cells, instead of neurospheres. The reported success of expanding NSCs in long-term adherent monolayer cultures is variable and may be due to differences in the substrates, serum-free media andgrowth factors used.17 Recently, protocols that have incorporated laminin as the substrate, along with an appropriate serum-free culture medium containing both EGF and bFGF have been able to support long-term cultures of neural precursors from mouse and human CNS tissues.30-32 These adherent cells proliferate and become confluent over the course of 5 - 10 days. To passage the cultures, cells are detached from the surface by enzymatic treatment and replated under the same conditions as the primary culture. It has been reported that NSCs cultured under adherent monolayer conditions undergo symmetric divisions in long-term culture.30,33 Similar to the neurosphere culture system, adherently cultured cells can be passaged multiple times and induced to differentiate into neurons, astrocytes and oligodendrocytes upon mitogen removal and exposure to a low serum-containing medium.

Several studies have suggested that culturing CNS cells in neurosphere cultures does not efficiently maintain NSCs and produces a heterogeneous cell population, whereas culturing cells under serum-free adherent culture conditions does maintain NSCs.17 While these reports did not directly compare neurosphere and adherent monolayer culture methods using the same medium, growth factors or extracellular matrix to evaluate NSC numbers, proliferation and differentiation potential, they emphasize that culture systems can influence the in vitro functional properties of NSCs and neural progenitors. It is important that in vitro methodologies for NSC research are designed with this caveat in mind, and with a clear understanding of what the methodologies are purported to measure.34-35

Immunomagnetic or immunofluorescent cell isolation strategies using antibodies directed against cell surface markers present on stem cells, progenitors and mature CNS cells have been applied to the study of NSCs. Similar to stem cells in other systems, the phenotype of CNS stem cells has not been completely determined. Expression, or lack of expression, of CD34, CD133 and CD45 antigens has been used as a strategy for the preliminary characterization of potential CNS stem cell subsets. A distinct subset of human fetal CNS cells with the phenotype CD133+ 5E12+ CD34- CD45- CD24-/lo has the ability to form neurospheres in culture, initiate secondary neurosphere formation, and differentiate into neurons and astrocytes.36 Using a similar approach, fluorescence-activated cell sorting (FACS)- based isolation of nestin+ PNA- CD24- cells from the adult mouse periventricular region enabled significant enrichment of NSCs(80% frequency in sorted population, representing a 100-fold increase from the unsorted population).37 However, the purity of the enriched NSC population was found to be lower when this strategy was reevaluated using the more rigorous Neural Colony-Forming Cell (NCFC) assay.38-39 NSC subsets detected at different stages of CNS development have been shown to express markers such as nestin, GFAP, CD15, Sox2, Musashi, CD133, EGFR, Pax6, FABP7 (BLBP) and GLAST40-45. However, none of these markers are uniquely expressed by NSCs; many are also expressed by neural progenitor cells and other nonneural cell types. Studies have demonstrated that stem cells in a variety of tissues, including bone marrow, skeletal muscle and fetal liver can be identified by their ability to efflux fluorescent dyes such as Hoechst 33342. Such a population, called the side population, or SP (based on its profile on a flow cytometer), has also been identified in both mouse primary CNS cells and cultured neurospheres.46 Other non-immunological methods have been used to identify populations of cells from normal and tumorigenic CNS tissues, based on some of the in vitro properties of stem cells, including FABP7 expression and high aldehyde dehydrogenase (ALDH) enzyme activity. ALDH-bright cells from embryonic rat and mouse CNS have been isolated and shown to have the ability to generate neurospheres, neurons, astrocytes and oligodendrocytes in vitro, as well as neurons in vivo, when transplanted into the adult mouse cerebral cortex.47-50 NeuroFluor CDr3 is a membrane-permeable fluorescent probe that binds to FABP7 and can be used to detect and isolate viable neural progenitor cells from multiple species.42-43

Multipotent neural stem-like cells, known as brain tumor stem cells (BTSCs) or cancer stem cells (CSCs), have been identified and isolated from different grades (low and high) and types of brain cancers, including gliomas and medulloblastomas.51-52 Similar to NSCs, these BTSCs exhibit self-renewal, high proliferative capacity and multi-lineage differentiation potential in vitro. They also initiate tumors that phenocopy the parent tumor in immunocompromised mice.53 No unique marker of BTSCs has been identified but recent work suggests that tumors contain a heterogenous population of cells with a subset of cells expressing the putative NSC marker CD133.53 CD133+ cells purified from primary tumor samples formed primary tumors, when injected into primary immunocompromised mice, and secondary tumors upon serial transplantation into secondary recipient mice.53 However, CD133 is also expressed by differentiated cells in different tissues and CD133- BTSCs can also initiate tumors in immunocompromised mice.54-55 Therefore, it remains to bedetermined if CD133 alone, or in combination with other markers, can be used to discriminate between tumor initiating cells and non-tumor initiating cells in different grades and types of brain tumors. Recently, FABP7 has gained traction as a CNS-specific marker of NSCs and BTSCs.42-43, 57

Both the neurosphere and adherent monolayer culture methods have been applied to the study of BTSCs. When culturing normal NSCs, the mitogen(s) EGF (and/or bFGF) are required to maintain NSC proliferation. However, there is some indication that these mitogens are not required when culturing BTSCs.57 Interestingly, the neurosphere assay may be a clinically relevant functional readout for the study of BTSCs, with emerging evidence suggesting that renewable neurosphere formation is a significant predictor of increased risk of patient death and rapid tumor progression in cultured human glioma samples.58-60 Furthermore, the adherent monolayer culture has been shown to enable pure populations of glioma-derived BTSCs to be expanded in vitro.61

Research in the field of NSC biology has made a significant leap forward over the past ~30 years. Contrary to the beliefs of the past century, the adult mammalian brain retains a small number of true NSCs located in specific CNS regions. The identification of CNS-resident NSCs and the discovery that adult somatic cells from mouse and human can be reprogrammed to a pluripotent state,62-68 and then directed to differentiate into neural cell types, has opened the door to new therapeutic avenues aimed at replacing lost or damaged CNS cells. This may include transplantation of neural progenitors derived from fetal or adult CNS tissue, or pluripotent stem cells. Recent research has shown that adult somatic cells can be directly reprogrammed to specific cell fates, such as neurons, using appropriate transcriptional factors, bypassing the need for an induced pluripotent stem cell intermediate.69 Astroglia from the early postnatal cerebracortex can be reprogrammed in vitro to neurons capable of action potential firing, by the forced expression of a single transcription factor, such as Pax6 or the pro-neural transcription factor neurogenin-2 (Neurog2).70 To develop cell therapies to treat CNS injuries and diseases, a greater understanding of the cellular and molecular properties of neural stem and progenitor cells is required. To facilitate this important research, STEMCELL Technologies has developed NeuroCult proliferation and differentiation kits for human, mouse and rat, including xenofree NeuroCult-XF. The NeuroCult NCFC Assay provides a simple and more accurate assay to enumerate NSCs compared to the neurosphere assay. These tools for NSC research are complemented by the NeuroCult SM Neuronal Culture Kits, specialized serum-free medium formulations for culturing primary neurons. Together, these reagents help to advance neuroscience research and assist in its transition from the experimental to the therapeutic phase.

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