Interferon-beta producing stem cell-derived immune cell therapy on … – Science Daily
By LizaAVILA
All causes of the most common form of liver cancer, hepatocellular carcinoma (HCC), are not yet known, but the risk of getting it is increased by hepatitis B or C, cirrhosis, obesity, diabetes, a buildup of iron in the liver, or a family of toxins called aflatoxins produced by fungi on some types of food. Typical treatments for HCC include radiation, chemotherapy, cryo- or radiofrequency ablation, resection, and liver transplant. Unfortunately, the mortality rate is still quite high, with the American Cancer Society giving a 5-year survival rate for localized liver cancer at 31%.
Hoping to improve primary liver cancer including HCC and metastatic liver cancer therapies, researchers from Japan began studying induced pluripotent stem (iPS) cell-derived immune cells that produced the protein interferon-? (IFN-). IFN- exhibits antiviral effects related to immune response, and two different antitumor activities, the JAK-STAT signaling pathway and p53 protein expression. IFN- has been used for some forms of cancer but problems like rapid inactivation, poor tissue penetration, and toxicity have kept it from being used extensively. To get over that hurdle, Kumamoto University researchers used iPS cell-derived proliferating myelomonocytic (iPS-ML) cells, which they developed in a previous research project. These cells were found to mimic the behavior of tumor associated macrophages (TAMS), which inspired the researchers to develop them as a drug delivery system for IFN- and evaluate the therapeutic effect on liver cancer in a murine model in vivo.
The researchers selected two cancer cell lines that were sensitive to IFN- treatment, one that easily metastasized to the liver after injection into the spleen and the other that produced a viable model after being directly injected into the liver. After injection, mice that tested positive for cancer (~80%) were separated into test and control groups. iPS-ML/IFN- cells were injected two to three times a week for three weeks into the abdomen of the test groups.
Livers with tumors were found to have higher levels of IFN- than those without. This was likely due to iPS-ML/IFN- cells penetrating the fibrous connective tissue capsule surrounding the liver ?serous membrane?and migrating toward intrahepatic cancer sites. The iPS-ML/IFN- cells did not penetrate non-tumorous livers, but rather stayed on the surface of the organ. Furthermore, concentrations of IFN- from 24 to 72 hours after iPS-ML/IFN- injections were found to be high enough to inhibit proliferation or even cause the death of the tumor cells.
Due to differences between species, mouse cells are not adversely affected by human IFN-, meaning that side effects of this treatment are not visible in this model. Fortunately, the researchers are working on a new model with the mouse equivalent of human iPS-ML/IFN, and testing its therapeutic abilities.
"Our recent research into iPS-cell derived, IFN- expressing myeloid cells should be beneficial for many cancer patients," says research leader Dr. Satoru Senju. "If it is determined to be safe for human use, this technology has the potential to slow cancer progression and increase survival rates. At this point, however, we still have much work ahead."
This research may be found in the Journal of Hepato-Biliary-Pancreatic Sciences online.
Story Source:
Materials provided by Kumamoto University. Note: Content may be edited for style and length.
More:
Interferon-beta producing stem cell-derived immune cell therapy on ... - Science Daily
‘Nigeria should harness potentials of regenerative medicine’ – Daily Trust
By raymumme
Dr. David Ikudayisi is the Medical Director, Glory Wellness & Regenerative Centre, a multi-specialty health care center, in Lagos and Abuja. Ikudayisi who is based in the United States said he is excited about the prospects of coming back home to help put Nigeria on the continental and global medical map through regenerative medicine. He also spoke on the controversy surrounding embroyonic stem cell therapy among others.
What is regenerative medicine allabout?
Regenerative Medicine is a branch of medicine that aims to restore normal function by repairing or replacing damaged or malfunctioning cells and tissues in patients who have lost tissue or organ function due to age, disease, or congenital defects. It comprises different components including, Platelet Rich Plasma (PRP) Therapy and Adult Stem Cell (ASC) Therapy, etc.
I was inspired into this branch of medicine when I was looking for alternative ways to alleviate my patients pain in USA without using addictive pain medications and frequent steroid injections. I discovered the benefits of the Platelet Rich Plasma and/or Adult Stem Cell Therapy for patients who were in need of joint pain relief, youthful appearance, or a restored sexual function.
In medical school, we were taught that the central nervous system rarely regenerates, that there is little or no hope for paralyzed patients, and that damaged brain tissue may be a permanent condition, just to name a few.
Nowadays, the re-growth of brain cells and improvements of neurological function in spinal cord injured patients have been documented. When applicable, adult stem cell treatment is basically a medical time machine. The results doctors see in medical practice every day is what keeps my drive for the advancement of regenerative medicine.
How will regenerative medicine help address health care challenges in Nigeria?
Nigeria has a lot of ways to go when it comes to health, as we are recording very poor health indices in recent times. This can be traced to not enough emphasizes on preventive medicine or regenerative medicine. We tend to lose hope at different stages of degrading health rather than come up with solutions that can be attainable no matter the initial cost. If taken without levity, Regenerative Medicine, as in Platelet Rich Plasma (PRP) Therapy & Adult Stem Cell (ASC) Therapy, can help reduce our mortality rate in Nigeria, thereby recording better health indices.
This branch of medicine holds answers to many questions and problems that we doctors used to believe had no solutions. Many medical conditions that we thought were not treatable are now treatable. We have ample evidence to show the potentials of regenerative medicines for ailments that have domineered our people. The use of these techniques will propel Nigerian healthcare to boundless heights if provided the opportunity.
Regenerative medicine has a vast amount of uses especially for people who seek to stop being dependent on taking medications daily, avoid surgery, feel younger and more energized, perform their marital enjoyment at older ages, and prevent the manifestation of some complications of diseases.
Many countries around the world are taking advantage of these therapies, and Nigeria should not be left behind. I know this is not an undertaking with quick payoff nationally, but I believe that with these innovations, Nigeria can be the centre for medical tourism in Africa. This is not a cheap option, as most novel innovations never are, but it will pay dividends in the long run, and we have seen proofs of that.
Some doctors are already offering regenerative medicine (PRP therapy and ASCT) in Nigeria. So, people dont have to travel abroad to benefit from regenerative medicine. Just ask your doctor if someone in your area is offering ASCT and PRP Therapy.
What illnesses does ASCT and PRP therapy treat?
The applications of ASCT are enormous, and there is much more to be discovered. To determine if this can be of use in a particular medical problem, just ask if there is a need for repair and/regeneration of any part of the human tissue/organ: if yes, then the ASCT with/without PRP therapy may be an option that will help. The exceptions are non-hematological cancer treatments, as these treatments with stem cells are under investigations/research using tissue engineering.
More specifically, these therapies can be used for issues like multiple joint pain, back pain, meniscal tears, ligament tears, avascular necrosis of the hip joints, facet arthropathy, hair thinning, erectile dysfunction, female sexual dysfunction, female urinary incontinence, cosmetic/aesthetic applications (vampire facial, vampire facelift, vampire breast and nipple lift); diabetes, hypertension, anti-aging (generalized treatment), chronic kidney disease, multiple sclerosis, cerebral palsy, spinal cord injury, COPD (lung disease) and infertility (helps to increase fertility chances and not serve as a cure), to mention a few.
Why is there controversy around embryonic stem cell therapy?
The ethical, religious and moral arguments for and against Embryonic Stem Cell use has been stressed for many years now. Stem cells possess the ability to make new cells needed in the body. Embryonic stem cells are an example of this. In the body, they are what we use to develop the cells we later go on to have.
Many scientists prefer it because of its endless possibilities to recreate virtually any type of cell in the body. However, it involves the use of embryos from day 6 to day 14; that is, a baby-to-be in the first two weeks of pregnancy or after In vitro fertilization (IVF). As you can see, this involves tampering with potential or future babies that are yet to be born. This has both religious and ethical issues, leading to the controversy around it.
What is the difference between adult stem cell therapy and cloning?
It is important to understand that there are three main types of stem therapies. In addition to Embryonic Stem Cell (ESC) therapy, there are also induced Pluripotent Stem Cells (iPSCs) therapy and Adult Stem Cells (ASC)therapy. iPSCs are produced in the lab by reprogramming adult cells to express embryonic stem cells characteristics, and Adult Stem Cells (ASC) are retrieved from individuals bone marrow, adipose (fat) or umbilical cord. Although ASCs can be used for a vast number of therapies, they do not possess the same capabilities as ESCs, but the downside of limited growth and differentiation makes ASCs applicable in medicine today.
Cloning on the other hand is the process of producing similar populations of genetically identical organisms to sometimes replace damaged or lost tissues or organs. Every single bit of their DNA is identical to the original specimen. Clones can happen naturally, like identical twins or triplets, or they can be made in the lab, like Dolly the sheep. Reproductive cloning for humans has been banned in several countries, and mainstream scientists consider it unethical.
Link:
'Nigeria should harness potentials of regenerative medicine' - Daily Trust
Researchers turn to the vascular system of plants to solve a major bioengineering problem blocking the regeneration … – Science Daily
By JoanneRUSSELL25
Researchers turn to the vascular system of plants to solve a major bioengineering problem blocking the regeneration ... Science Daily ... to establish a vascular system that delivers blood deep into the developing tissue. Researchers have now successfully turned to plants, culturing beating human heart cells on spinach leaves that were stripped of plant cells. ... "The spinach leaf ... |
Cellect Succeeds In First Stem Cell Transplant (APOP) – Investopedia
By daniellenierenberg
Investopedia | Cellect Succeeds In First Stem Cell Transplant (APOP) Investopedia It includes more than half the stem cell transplant procedures, including bone marrow transplant, resulting in a serious rejection disease called Graft-versus-Host-Disease (GvHD). GvHD is a medical disorder which results from receipt of transplanted ... Cellect Announces Successful First Cancer Patient Stem Cell Transplant Why Cellect Biotechnology Ltd. (APOP) Stock Is Soaring Today |
See the article here:
Cellect Succeeds In First Stem Cell Transplant (APOP) - Investopedia
Protein Found in Young Blood Could Be The Key To Fight Aging – Wall Street Pit
By NEVAGiles23
As people age, so does their blood. The question is: what exactly is in the blood of older people that makes it age? And in the same light, what is in the blood of younger people that can help rejuvenate old blood?
The idea of using young blood to rejuvenate old blood was not an automatic conclusion, of course. While it does seem logical, it remained a theory until tests that involved conjoining (i.e. stitching together) of old and young mice for the purpose of swapping blood revealed that the concept did have merit. With shared blood, the health of younger mice deteriorated while the health of older mice improved.
Another kind of experiment done was non-invasive blood swapping using tubes. The results were similar, though different explanations emerged for the change in health conditions of both old and young mice. When conjoined, the mice shared more than just blood; their organs got affected too. In non-invasive blood swapping, the old blood got diluted.
While these experiments were done on mice, theres a chance they might work in people as well. However, this involves blood donation from young people, which might mean the supply will be limited when it comes to fulfill demand.
As an alternative, a research team at Germanys University of Ulm led by Hartmut Geiger turned to stem cells, specifically, what are being referred to as mother stem cells those stem cells in the bone marrow that produce red and white blood cells, and whose number become fewer and fewer as a person ages. With fewer of these cell-generating cells, older people become more susceptible to conditions like anemia and heart disease. They become less capable of fighting infection as well.
By examining mice bone marrow, Geigers team discovered that older mice have considerably lower levels of a protein known as osteopontin. To check the effect of this protein on blood stem cells, they injected stem cells into mice that had low levels of osteopontin. What happened was, the cells aged much quicker.
However, when they mixed older stem cells with osteopontin and a protein that activates osteopontin, the old stem cells started producing white blood cells as if they were young stem cells. This suggests that osteopontin might indeed have a hand in rejuvenating old stem cells and making them behave as if they were young again.
While majority of blood rejuvenation efforts focus on the liquid part of blood (or plasma), Geiger believes blood cells might also play a vital role since cells can move better in the bodys tissues.
Following the initial results of their experiments, the team is now working on developing a drug that contains osteopontin and its corresponding protein activator. The hope is that this drug can promote youthful behavior in blood stem cells and boost the number of mother stem cells. Ultimately, this can help in the treatment of age-related blood disorders, and possibly boost the immune system of the elderly too so they dont get sick as easily.
Details of the study have been reported in The EMBO Journal.
Read more:
Protein Found in Young Blood Could Be The Key To Fight Aging - Wall Street Pit
Lungs Play Previously Unknown Role in Blood Production – Sci-News.com
By Dr. Matthew Watson
Using video microscopy in a living mouse lung, a team of researchers at the Universities of California, San Francisco (UCSF) & Los Angeles (UCLA), has revealed that the lungs play a previously unrecognized role in blood production.
Visualization of resident megakaryocytes in the lungs. Image credit: Emma Lefranais et al, doi: 10.1038/nature21706.
The team, headed by UCSF Professor Mark R. Looney, found that the lungs produced more than half of the platelets blood components required for the clotting that stanches bleeding in the mouse circulation.
In another finding, the team also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.
This finding definitely suggests a more sophisticated view of the lungs that theyre not just for respiration but also a key partner in formation of crucial aspects of the blood, Prof. Looney said.
What weve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.
The study was made possible by a refinement of a technique known as two-photon intravital imaging.
The authors were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature.
When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up, said team member Dr. Emma Lefranais, from the UCSF Department of Medicine.
More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouses total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed.
Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature estimated at 1 million per mouse lung.
Proposed schema of lung involvement in platelet biogenesis. The role of the lungs in platelet biogenesis is twofold and occurs in two different compartments: (a) platelet production in the lung vasculature; after being released from the bone marrow or the spleen, proplatelets (a1) and megakaryocytes (a2) are retained in the lung vasculature, the first capillary bed encountered by any cell leaving the bone marrow, where proplatelet formation and extension and final platelet release are observed; (b) mature and immature megakaryocytes along with hematopoietic progenitors are found in the lung interstitium; in thrombocytopenic environments, hematopoietic progenitors from the lung migrate and restore bone marrow hematopoietic deficiencies. Image credit: Emma Lefranais et al, doi: 10.1038/nature21706.
The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow.
To address these questions, Prof. Looney, Dr. Lefranais and their colleagues conducted a clever set of lung transplant studies.
First, they transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature.
This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.
In another experiment, the team transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts.
The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation much longer than the lifespan of individual megakaryocytes or platelets.
This indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouses low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.
Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells.
Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells.
These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.
To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia, Prof. Looney said.
The findings were published online March 22, 2017 in the journal Nature.
_____
Emma Lefranais et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature, published online March 22, 2017; doi: 10.1038/nature21706
This article is based on text provided by the University of California, San Francisco.
Continue reading here:
Lungs Play Previously Unknown Role in Blood Production - Sci-News.com
Living Organ Donors: Proposed Tax Deduction Could Help Defray Donation Expenses – Hartford Courant
By JoanneRUSSELL25
The decision to become a living organ donor is a significant one and, among the many factors to weigh, donors should consider potential financial consequences of their altruism.
Medical costs associated with organ, tissue and bone marrow donations don't fall on the donor; they typically are paid by the recipient and often covered by insurance, Medicare or Medicaid.
But other related expenses including travel, lodging and loss of wages due to time out of work are the donor's responsibility.
Most of the roughly 6,000 living donations that occur annually are between relatives and close friends, people who have a vested interest in the recipient's outcome, according to the U.S. Department of Health and Human Services (HHS).
But even people who wouldn't hesitate to help a loved one should know about potential costs.
When Sally McCartin of North Branford donated a kidney to a fellow "hockey mom" in 2013, she knew she'd have to take time off from her job at the state's Department of Revenue Services.
"I was worried about the first two weeks that I would be out of work because I had used up all my sick time getting the necessary testing done to donate," she says. "Initially, I would have gone with no pay for the first two weeks."
The recipient of her kidney offered to cover McCartin's loss of wages, but the expense ultimately was covered by financial donations from McCartin's coworkers and contributions from her union, so she bore none of the cost.
For others, out-of-pocket expenses can be problematic and may deter some from donating altogether, says Sen. Martin Looney, D-New Haven. He proposed legislation in January that would help ease some of the burden.
Under his bill, people who donate organs or bone marrow after Jan. 1, 2017, could deduct up to $10,000 from their income, under the state personal income tax, to cover unreimbursed costs of travel, lodging and lost wages they incur as a result of donating. The bill also aims to allow state employees, beginning in 2018, to take up to 30 days of paid leave from work for organ donation and up to seven days of paid leave for bone marrow donation.
The legislation, co-sponsored by Sen. Catherine Osten, D-Columbia, is before the General Assembly's Public Health Committee and slated to receive a public hearing. It's intended to "limit potential barriers to people agreeing to be a live donor," Looney says.
The matter hits close to home for the senator, who suffered from kidney failure and received a kidney donation from a live donor in December. Nineteen states already have similar laws on the books, Looney says.
Some donors may have some expenses covered by their own insurance, depending on their plan, he says, but not all do.
"In some cases, the out-of-pocket expenses are minimal to the donor, and in other cases they can be substantial," he says, especially when it comes to missed work. "The donor is going to be out of work probably for a minimum of two weeks after the procedure. That would probably be the biggest hardship of all."
Many things can be donated by living donors, according to the HHS, including six vital organs: heart, kidneys, pancreas, lungs, liver and intestines. (In some cases a portion of the organ, such as the liver, is donated. Living heart donations are rare but happen. They occur when a donor has a pulmonary condition that necessitates removal of the heart and lungs for new ones lungs-only operations are considered riskier but the donor's heart is in good enough condition to be transplanted in another patient.)
Donors also may give certain tissues including skin, cornea and blood vessels as well as bone marrow, stem cells and umbilical cord blood.
April has been dubbed "National Donate Life Month," an effort by nonprofit advocacy group Donate Life America to encourage people to register as organ, eye and tissue donors.
About 20 to 25 living donations occur annually at the Hartford Hospital Transplant Program, according to registered nurse and Living Donor Transplant Coordinator Kari Rancourt. Most of them are kidney transplants.
"We do talk a little [with prospective donors] about out-of-pocket expenses," she says. Some donors get help covering costs through social fundraising platforms like GoFundMe, she says.
There also are foundations that offer grants to help would-be donors afford travel and lodging, she adds, which have "helped limit barriers to donations."
McCartin, who donated at Yale-New Haven Hospital, says that she did have to consider the potential expense but that wouldn't have stopped her from donating. She is so passionate about it, she recently began Kid-U-Not, a Connecticut chapter of the American Living Organ Donor Fund that raises funds to assist donors.
"I felt that, if I was healthy enough to donate, then it was a no-brainer," she says. "How could I not help a single mom of three children? I would hope that if I was ever in the same situation someone would step up for me."
Read the original here:
Living Organ Donors: Proposed Tax Deduction Could Help Defray Donation Expenses - Hartford Courant
How Big Data is Being Mobilized in the Fight Against Leukemia – Drug Discovery & Development
By JoanneRUSSELL25
Healthy cell function relies on well orchestrated gene activity. Via a fantastically complex network of interactions, around 30,000 genes cooperate to maintain this delicate balance in each of the37.2 trillion cellsin the human body.
Broadly speaking, cancer is a disruption of this balance by genetic changes, or mutations. Mutations can trigger over-activation of genes that normally instruct cells to divide, or inactivation of genes that suppress the development of cancer. When a mutated cell divides, it passes the mutation down to its daughter cells. This leads to the accumulation of non-functioning, abnormal cells that we recognise as cancer.
Our laboratoryis focused on understanding how one particular cancer chronic myeloid leukaemiaor CML works. Each year more than 700 patients in the UK andover 100,000worldwide are diagnosed with CML. After recent advances,almost 90%of patients under the age of 65 now survive for more than five years.
Sign Up for DDD's Webinar on Multicomponent Amorphous Solid Dispersion Systems on March 28th!:http://buff.ly/2n5iEqr
But in the vast majority of patients CML is currently incurable and lifelong treatment means that patients must live with side effects and the chance of drug resistance arising. With increasing numbers of CML patients surviving (and treatment costing between 40,000 and 70,000 per patient a year), increasing strain is being placed on health services.
A single mutation
CML is perhaps unique in cancers in that a single mutation, namedBCR-ABL, underlies the disease biology. This mutation originates in a singleleukaemic stem cell, but is then propagated throughout the blood and bone marrow as leukaemia cells take over and block the healthy process of blood production. The presence of BCR-ABL affects the activity of thousands of genes, in turn preventing these cells from fulfilling their normal function as blood cells.
Drugsthat specifically neutralise the aberrant effects of this mutation were introduced to the clinic from the early 2000s. These drugs have revolutionised CML patient care. Many are now able to live relatively normal lives with their leukaemia under good control.
But while these drugs kill the more mature daughter cells of the originally mutated leukaemia stem cell, they have not fully lived up to their initial billing as magic bullets in the fight against cancer. This is because the original seed population of leukaemic stem cellsevade therapy,lying dormant in the bone marrowto stimulate new cancer growth when treatment is withdrawn.
To truly cure CML we must expose, understand the inner workings of, and uproot the leukaemia stem cells. And to do this, we need to learn more about them. How do they survive the treatment that so readily kills their more mature counterparts? Which overactive or inactivated genes protect them?
We believe that the answers to these questions lie in the analysis of biological big data. Genome-scale technologies now allow scientists to measure the activity (or expression) of every gene in the genome simultaneously, in any given population of cells, or even at the level of a single cell. Comparison of expression data generated from leukaemia stem cells with the same data generated from healthy blood stem cells will reveal single genes or networks of genes potentially targetable in the fight against leukaemia.
Big data to the rescue
In a project funded by Bloodwise and the Scottish Cancer Foundation, we have createdLEUKomics. This online data portal brings together a wealth of CML gene expression data from specialised laboratories across the globe, including our own at the University of Glasgow.
Our intention is to eliminate the bottleneck surrounding big data analysis in CML. Each dataset is subjected to manual quality checks, and all the necessarycomputational processingto extract information on gene expression. This enables immediate access to and interpretation of data that previously would not have been easily accessible to academics or clinicians without training in specialised computational approaches.
Consolidating these data into a single resource also allows large-scale, computationally-intensive research efforts by bioinformaticians (specialists in the analysis of big data in biology). From a computational perspective, the fact that CML is caused by a single mutation makes it an attractive disease model for cancer stem cells. However, existing datasets tend to have small sample numbers, which can limit their potential.
The more samples available, the higher the power to detect subtle changes that may be crucial to the biology of the cancer stem cells. By bringing all the globally available CML datasets together, we have significantly increased the sample size, from two to six per dataset to more than 100 altogether. This offers an unprecedented opportunity to analyse gene expression data to expose underlying mechanisms of this disease.
As of March 2017, theportalis up and running in the public domain. We are planning to tour Scotland and present at international conferences, aiming to train researchers in how best to exploit this new resource. Ultimately, we hope that this tool will lead to new ideas and approaches, and attract more funding, in the fight against CML. And while we continue to expand our representation of CML data in real time from research centres all over the world, we also plan to begin incorporating data from other types of leukaemia.
In recent years, targeted therapies have becomehugely importantin cancer research. By providing these data to the CML research community withinLEUKomics, we hope to mobilise new research into cancer-causing leukaemic stem cells, and ultimately design treatments to target them without affecting healthy cells. Our database provides a critical stepping stone in this process.
Here is the original post:
How Big Data is Being Mobilized in the Fight Against Leukemia - Drug Discovery & Development
Neural Crest Stem Cells From Skin Without Genetic Modifications … – UB School of Medicine and Biomedical Sciences News
By daniellenierenberg
Stelios Andreadis, PhD, is leading a team of researchers who have discovered how to convert adult skin cells into stem cells without modifying their genetics.
UB researchers have found that adult skin cells can be converted into neural crest cells without any genetic modification.
The discovery, which was several years in the making, proves that these stem cells can yield other cells that are present in the spinal cord and brain.
The applications could be very significant, ranging from studying genetic diseases in a dish to generating possible regenerative cures from a patients own cells.
Its actually quite remarkable that it happens, says Stelios Andreadis, PhD, professor of biomedical engineering, who recently published a paper on the results, titled Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates, in the journal Stem Cells.
The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.
This image shows Keratinocyte-derived neural crest stem cells turning into neurons as shown by typical neuronal morphology.
Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.
In medical applications this has tremendous potential because you can always get a skin biopsy, says Andreadis, who is also professor and chair of the Department of Chemical and Biological Engineering in the School of Engineering and Applied Sciences.
We can grow the cells to large numbers and reprogram them without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources, he says.
The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin.
The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprogramming to the pluripotent state.
The discovery was a gradual process, taking almost five years, Andreadis says, as successive experiments kept leading to something new.
It was one step at a time. It was a very challenging task that involved a wide range of expertise and collaborators to bring it to fruition, he says.
Collaborators include:
Andreadis credits the persistence of his then-doctoral student, Vivek K. Bajpai, for sticking with it.
He is an excellent and persistent student, Andreadis says. Most students would have given up.
The research was supported by grants from the National Institutes of Health (NIH).
Andreadis also credits a seed grant from UBs Office of the Vice President for Research and Economic Developments IMPACT program that enabled part of the work.
The work recently received a $1.7 million NIH grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinsons-like symptoms in a mouse model of hypomyelinating disease.
This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases, Andreadis says. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further.
Follow this link:
Neural Crest Stem Cells From Skin Without Genetic Modifications ... - UB School of Medicine and Biomedical Sciences News
Three women blinded after clinical trial went wrong – Normangee Star
By LizaAVILA
But its always been clear that they could be risky too, especially if theyre not used carefully. The LCSB team has published its results in the scientific journal PLOS Biology.
This study shows that for the first time, targeting the proliferating tumor mass and dormant cancer stem cells with combination therapy effectively inhibited tumor growth and prevented metastasis compared to monotherapy in mice, said Wang, who is a member of the UCLA Jonsson Comprehensive Cancer Center and of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. However, as of April 2016, new rules on human cells and tissue require FDA oversight and approval for such procedures.
Although the women had moderate vision loss prior to the stem cell treatments, a year later their vision ranged from total blindness to 20/200, which is considered legally blind.
NPR contacted the FDA, and was told by a spokeswoman that the agency is now finalizing a series of new guidelines regulating how clinics could use stem cells for treatment purposes. So far, however, scientists only partially understand how the body controls the fate of these all-rounders, and what factors decide whether a stem cell will differentiate, for example, into a blood, liver or nerve cell. He wrote an editorial accompanying the two papers.
As reported Wednesday in the New England Journal of Medicine, one of the women, a 72-year-old, went completely blind after doctors injected stem cells into her eye in an attempt to cure the disease.
But within a week of starting the off-the-charts dangerous therapy at an American clinic, the patients suffered complications.
Two of the patients sought treatment at the universitys hospital for the complications they suffered. The agency also noted that it had previously issued a warning to patients. She said that they were treating patients with their own stem cells.
In addition to charging a fee for treatment, there were several other red flags in the Florida cases that consumers should watch for when considering participation in a clinical trial, Goldberg said. They sought treatment at a Florida clinic that had announced a study to treat the condition on clinicaltrials.gov, a federal database of research studies.
Within days of the stem cell injections she was almost blind and ultimately progressed to complete blindness. Their attorney, Andrew Yaffa of Coral Gables, said that the case was resolved to the mutual satisfaction of the parties but that neither he nor his clients could comment beyond that.
She acknowledged, however, that the clinic had been performing the stem cell procedures.
Shoddy preparation of the stem cells may have led to some of the complications, said the study authors. We feel very confident about the procedures that we do, and weve had great success in many different indications. We believe that regenerative medicine / cellular therapeutics will play a large role in positively changing the natural history of diseases ultimately, we contend, lessening patient burdens, as well as reducing the associated economic impact disease imposes upon modern society.
The body produces a variety of stem cells. It is also costly, at almost $900,000 to develop and test the iPS cells for the first trial, Takahashi adds.
Whatever happened, experts said there was no evidence to suggest the procedure would have helped restore vision, since so little study has been done on whether adipose-derived stem cells can mature into the kinds of retinal cells that are involved in macular degeneration.
This represents a landmark, says Daley. But it proved too slow and expensive, says Shinya Yamanaka of Kyoto University in Japan, who first discovered how to create iPS cells and is a co-author of the NEJM paper. The registry may be useful as a starting point, but patients should then discuss potential trials with qualified physicians, an academic medical center.
A second patient was supposed to be treated, but transplantation was called off after the cells were found to have potential genetic problems. The cells were extracted their from fat, mixed with blood plasma and injected into their eyes.
Even though the safety and effectiveness of this procedure is unknown, all three patients received injections in both eyes. Dr. Thomas Albini of the University of Miami examined the women after they were treated at a clinic in Florida.
Before the procedure, all three women still had at least some vision. Medical experts said the episode raises questions about whether the government and doctors are doing enough to protect patients from the dangers of unapproved therapies.
View post:
Three women blinded after clinical trial went wrong - Normangee Star
Human heart muscle made from stem cells – Free Press Journal
By Sykes24Tracey
By FPJ Bureau|Mar 20, 2017 06:26 pm
Melbourne: Scientists have created a functional beating human heart muscle from stem cells, a significant step forward in cardiac disease research. Researchers at The University of Queensland (UQ) in Australia developed models of human heart tissue in the laboratory so they can study cardiac biology and diseases in a dish.
The patented technology enables us to now perform experiments on human heart tissue in the lab, said James Hudson from the UQ School of Biomedical Sciences. This provides scientists with viable, functioning human heart muscle to work on, to model disease, screen new drugs and investigate heart repair, said Hudson.
In the laboratory we used dry ice to kill part of the tissue while leaving the surrounding muscle healthy and viable, Hudson said. We found those tissues fully recovered because they were immature and the cells could regenerate in contrast to what happens normally in the adult heart where you get a dead patch. Our goal is to use this model to potentially find new therapeutic targets to enhance or induce cardiac regeneration in people with heart failure, he said.
Studying regeneration of these damaged, immature cells will enable us to figure out the biochemical events behind this process. Hopefully we can determine how to replicate this process in adult hearts for cardiovascular patients, said Hudson.
Each year, about 54,000 Australians suffer a heart attack, with an average of about 23 deaths every day, researchers said. Heart Foundation Queensland CEO Stephen Vines said the charity was excited to fund such an important research project.
Heart attack survivors who have had permanent damage to their heart tissue are essentially trying to live on half an engine, Vines said. The research will help unlock the key to regenerating damaged heart tissue, which will have a huge impact on the quality of life for heart attack survivors, he added.
Previous Article Bhagalpur University cancels LLB degree of Delhi's former law minister Jitender Singh Tomar
Next Article Toilet paper toll: How Beijing is aiming to reduce paper wastage
Read the rest here:
Human heart muscle made from stem cells - Free Press Journal
Stem cell treatments can go wrong – Jamaica Observer
By NEVAGiles23
Stem cells are the foundation of all our body cells before they differentiate to become specialised cells that grow into our tissues and organs, such as kidney cells, muscle cells, nerve cells, and so on.
They commonly come from two sources: The embryo (embryonic stem cells formed in early development after the human egg is fertilised by a sperm); and adult tissue (adult stem cells, such as those existing in bone marrow to later differentiate to form red blood cells, white blood cells and other components of the blood).
The use of human embryonic stems cells for treatment or research is often frowned upon by some people, as they regard the human embryo as a person that should not be discarded after such endeavours. Consequently, much scientific work has recently been focused on the use of adult stem cells.
THE USE OF STEM CELLS
Stem cells may be beneficial in treating diseases that are amenable to cell replacement. However, this is still a young science, and belief that a particular treatment helps two or three people does not convince the scientific community or the whole society that the treatment will work for everyone so afflicted.
Scientific proof comes from conducting clinical trials, the international gold standard often involving hundreds of people so afflicted and comparing them with an equivalent number of people not afflicted to determine whether a treatment really works for those who receive it.
Whilst many stem cell research projects are currently being conducted in various centres around the world to determine whether they produce benefits, and what may be the possible risks involved, there are also medical clinics that are using stem cells not in a registered research project, but rather in the actual treatment of affected people.
TREATMENT CAN CAUSE HARM
A recent report in the highly respected New England Journal of Medicine informed that three elderly women in Florida had been blinded by an unproven treatment.
They had signed up for a purported clinical trial in 2015 for which they had to pay US$5,000 each. Before surgery, the vision in their eyes varied from 20/30 to 20/200, but within one week after surgery, they experienced a variety of complications, including vision loss, detached retinas and bleeding into their eyes, resulting in total blindness.
The authors of the article from the Standard University School of Medicine sought to make patients, doctors and the various regulatory agencies aware of the risks of such a minimally regulated, patient-funded research. It stated that some clinics appeal to patients that are desperate for care and who hope that stem cells will be their answer, but as in the case of these women, some of these current enterprises are very dangerous.
At this particular clinic, fat cells were taken from the patients abdomens and processed to obtain stem cells which were then injected into their eyes. The patients reported that the entire process took less than one hour. The patients had both eyes treated at once, even though most doctors would opt for a conservative approach to observe how the first eye responds.
THE NEED FOR THE REGULATION OF RESEARCH
The article stated that while there is a lot of well-founded evidence for the positive potential of stem cell treatment for many human diseases, such treatments should be conducted in a well-designed clinical trial based on pre-clinical research.
The treatment done for the women lacked nearly all the components of a properly designed clinical trial, including a hypothesis based on laboratory experiments, the involvement of a control group of people and a treatment group, the safe collection of data, the masking of clinical and patient groups, and plans for follow-up.
Clinics offering stem cell treatments exist in Jamaica, The Bahamas and Cuba. However, while both The Bahamas and Cuba have developed regulations that stipulate in law the conditions to be met for stem cell treatments and research within their jurisdictions, Jamaica has developed no such regulation.
THE MEDICAL ACT DOES NOT PROVIDE PROTECTION
The Medical Act of Jamaica was passed in 1976, but does not mention or provide any guidance or protection regarding research with human participants.
Its focus was to: Register medical practitioners; appoint examiners to conduct exams for people applying for registration, and ensure the maintenance of proper professional conduct by practitioners.An amendment in 2004 added the requirement of continuing medical education for practitioners.
Guyana and St Lucia are the only countries in the Caribbean that have joined the progressive countries who all have legislation governing research with human participants within their borders. Regulations should stipulate the requisite conditions, including that treatment and research be monitored by an appropriate ethics committee to meet all international standards.
Without this, vulnerable people seeking health benefits will unknowingly continue to subject themselves to risks of harm without the protection that proper regulations can provide.
Derrick Aarons MD, PhD is a consultant bioethicist/family physician, a specialist in ethical issues in medicine, the life sciences and research, and is the Ethicist at the Caribbean Public Health Agency (CARPHA). (The views expressed here are not written on behalf of CARPHA)
Continued here:
Stem cell treatments can go wrong - Jamaica Observer
Unproven Stem Cell Treatment Blinds 3 Florida Women – ClickLancashire
By raymumme
The Food and Drug Administration recommends that people who consider getting a stem cell treatment need to make sure it has been approved or is being studied in a clinical trial that federal health regulators have allowed. The kind that have generated the most excitement - and controversy - are human embryonic stem cells, which are derived from early human embryos and can be coaxed to become any kind of cell in the body. After 20 years of research, Italian scientists recently received European regulatory approval for a stem cell-based treatment for a type of blindness that results from damage to the cornea, the surface of the eye. The fat tissue was then processed with enzymes with the goal of obtaining stem cells.
However, they immediately suffered complications, including retinal detachment and hemorrhage, which caused total loss of eyesight. "It's just not the case".
None of the women are named in the study.
In 2013, the company listed a trial on ClinicalTrials.gov titled, "Study to Assess the Safety and Effects of Cells Injected Intravitreal in Dry Macular Degeneration", according to the ClinicalTrials.gov site. Both lawsuits were settled, with the women receiving payments.
He warned that patients could be misled by "rogue clinics" which failed to distinguish between the many different types of stem cell. Those efforts have stalled, however. She stated that this was not a drug it was a simple procedure. Albini says the complications could have come from injecting a contaminant into the eye, or from the fact that the stem cells may have turned into myofibroblasts after the injections, which are cells associated with scarring.
The cases show that patients need to be warned that something that "sounds too good to be true may indeed be too good to be true and may even be disgusting", Albini says.
The company appeared to have plans to do more such procedures. Small molecule inhibitors for cancer stem cells in this study are available or being utilized in clinical trials for other diseases. The two women told Albini that they did not recall signing documents other than the single page form.
"Patients and physicians in the United States should be made aware that not all "stem cell" clinics are safe, and that "stem therapy" as provided in private clinics in the U.S. is unproven and potentially harmful", says Thomas Albini at the University of Miami's Bascom Palmer Eye Institute, Florida, who subsequently treated two of the women.
Each woman paid $5,000 for the procedure.
The doctors say patients should also check if anything purporting to be a clinical trial is affiliated with an academic medical centre and inform themselves about stem cell treatments.
"These women had fairly functional vision prior to the procedure. and were blinded by the next day", said ophthalmologist Dr Thomas Albini of the University of Miami, whose team examined the women after their treatment at a clinic in Florida. In the case of the eye injections, the clinic injected both eyes at once, which is highly unusual and unsafe for an experimental treatment.
The trial was not preceded by laboratory experiments and lacked comparison between treated patients and "control group" participants given a dummy therapy.
It's still not clear what went wrong, but the report says the treatment raised several red flags from the beginning.
But even if executed correctly, there is no evidence suggesting that the procedure could help restore vision, Goldberg and Albini said. A year later, the patient suffered none of the additional vision loss that would be common with the condition. iPS stem cells have a body of research behind their potential healing abilities, while the fat-based cells used in the procedures do not. It offers stem cell treatments for a variety of diseases and injuries, according to the company's website.
"With this new and exciting study, Dr. Wang and his team have provided the building blocks for understanding the cellular and genetic mechanisms behind squamous cell carcinoma", said Dr. Paul Krebsbach, dean of the UCLA School of Dentistry. "Doing the procedure in rats might have shown whether there are safety problems".
Without regulation of stem cell isolation and delivery processes at stem cell clinics, it's hard to know whether their cocktails contain harmful chemicals leftover from the isolation process - or whether they contain stem cells at all. In a regulatory filing, it reported that its techniques can treat chronic obstructive pulmonary disease, hip and knee conditions, diabetes, multiple sclerosis, Parkinson's disease, autism, colitis, and lupus.
Excerpt from:
Unproven Stem Cell Treatment Blinds 3 Florida Women - ClickLancashire
Young blood: Scientists say this protein could be key to reversing aging process – Yahoo News
By NEVAGiles23
The suggestion that young blood may be the key toreversingsome of the negative aspects of aging sounds like the setup to a horror movie. In reality, however, itrefers to some groundbreaking work being carried out byscientists at the University of Ulm in Germany.
Theyve been examining the ways that old blood can be made young again, and they hypothesize that it might help fight some of the effects of aging.To achieve this, theyve discovereda protein capable of boosting blood stem cells, which prompts them to act like the stem cells of younger people.
More: Scientists may have discovered how to reverse the natural aging process
Older stem cells have several disadvantages, Dr. Hartmut Geiger, co-author of a paper describing the work, told Digital Trends. Theyresult in fewer red blood cells, and fewer of an important immune cell that fights infection. They also tend to produce more leukemia, which is a cancer of the blood. All of this is linked, at least in part, to the aging of stem cells. If you have younger stem cells, we think that we can reverse some of these effects.
Older stem cells tend to possess these negative characteristics thanks to the declining number of so-called mother stem cells in our bone marrow as we age. This decline triggers the effects Geiger describes.
In trials with mice, Geiger and his team discovered that older mice have lower levels of a protein called osteopontin. They decided to testthe effect of this protein on blood stem cells.
We took the stem cells from aged mice, incubated them with the osteopontin protein, and then gave them back, he continued.These blood stem cells, which had come from older animals, were found to have a lot of the features of stem cells coming from much younger animals in terms of function.
Its still early days for the research, but the suggestion that osteopontin could make stem cells behave in a more youthful way is certainly promising. The team is now developing a drug made up of osteopontin and a protein for activating it.
Hopefully human trials can follow in the not-too-distant future while were still around to benefit from them.
Link:
Young blood: Scientists say this protein could be key to reversing aging process - Yahoo News
Scientists know how to grow human heart tissue – Institute …
By Dr. Matthew Watson
Scientists used stem cells to grow human heart tissue that contracted spontaneously in a petri dish marking progress in the quest to manufacture transplant organs.
A team from the University of Pittsburgh, Pennsylvania, used induced pluripotent stem (iPS) cells generated from human skin cells to create precursor heart cells called MCPs. iPS cells are mature human cells reprogrammed into a versatile, primitive state from which they can be prompted to develop into any kind of cell of the body. The primitive heart cells created in this way were attached to a mouse heart scaffold from which the researchers had removed all mouse heart cells, they wrote in the journal Nature Communications.
The scaffold is a network of non-living tissue composed of proteins and carbohydrates to which cells adhere and grow on. Placed on the 3D scaffold, the precursor cells grew and developed into heart muscle, and after 20 days of blood supply the reconstructed mouse organ began contracting again at the rate of 40 to 50 beats per minute, said a University of Pittsburgh statement.
It is still far from making a whole human heart, added senior researcher Lei Yang. Ways have to be found to make the heart contract strongly enough to pump blood effectively and to rebuild the hearts electrical conduction system. However, we provide a novel resource of cells iPS cell-derived MCPs for future heart tissue engineering, Yang told AFP by email. We hope our study would be used in the future to replace a piece of tissue damaged by a heart attack, or perhaps an entire organ, in patients with heart disease.
According to the World Health Organisation, an estimated 17 million people die of cardiovascular ailments every year, most of them from heart disease. Due to a shortage of donor organs, end-stage heart failure is irreversible, said the study. More than half of patients with heart disease do not benefit from drugs. Heart tissue engineering holds a great promise based on the reconstruction of patient-specific cardiac muscle, the researchers wrote.
Last month, scientists in Japan said they had grown functional human liver tissue from stem cells in a similar process. Creating lab-grown tissue to replenish organs damaged by accident or disease is a Holy Grail for the pioneering field of stem cell research. Until a few years ago, when iPS cells were created, the only way to obtain stem cells was to harvest them from human embryos. This was controversial because it required the destruction of the embryo, a process to which religious conservatives and others object.
Source: http://news.sudanvisiondaily.com
As the Chief Doctor of the Institute of Cell Therapy, Y.V.Gladkikh, MD, PhD, Dr. med. sc. commented: In addition to laboratory success in obtaining the functional cardiac tissue, currently there is evidence of successful implantations of heart valves and blood vessels fragments, grown from stem cells, to patients. And in 2012, the Ministry of Health of Ukraine officially approved method of treatment of critical limbs ischemia with the use of cell preparation Angiostem, developed by the biotechnological laboratory of the Institute of Cell Therapy.
See original here:
Scientists know how to grow human heart tissue - Institute ...
Measuring Heart Toxicity of Cancer Drugs | Technology Networks – Technology Networks
By LizaAVILA
A stem cell-derived heart muscle cell. Proteins that are important for muscle cell contraction are highlighted in red and green, and cell nuclei are blue. Credit: Joseph C. Wu, M.D., Ph.D., Stanford Cardiovascular Institute
Using human heart cells generated from adult stem cells, researchers have developed an index that may be used to determine how toxic a group of cancer drugs, called tyrosine kinase inhibitors (TKIs), are to human cells. While 26 TKIs are currently used to treat a variety of cancers, some can severely damage patients hearts, causing problems such as an irregular heartbeat or heart failure.
For the study, reported February 15 in Science Translational Medicine, the researchers used stem cell-derived heart cells from 13 volunteers to develop a cardiac safety index that measures the extent to which TKIs kill or alter the function of heart cells. They found that the TKIs' toxicity score on the index was generally consistent with what is known about each drug's heart-related side effects.
This work follows on the heels of an earlier study from the same research team, published in Nature Medicine, in which they assessed the heart cell toxicity of doxorubicin, a chemotherapy drug that also causes heart-related side effects, including heart failure. In that study, the researchers used stem cell-derived heart cells from women with breast cancer to correctly predict how sensitive each womans heart cells were to doxorubicin.
Such tests could ultimately help the pharmaceutical industry identify drugs that cause heart-related side effects earlier in the drug development process and help the Food and Drug Administration (FDA) during the drug review and approval process, said the study's senior author Joseph C. Wu, M.D., Ph.D., director of the Stanford Cardiovascular Institute.
I hope this research will be helpful for individual patients, once we further implement precision medicine approaches, he added.
Ranking Heart Toxicity
To assess the potential risk of heart toxicity for drugs in development, pharmaceutical companies use laboratory tests involving animals (usually rats or mice) or cells from animals or humans that are engineered to artificially express heart-related genes. Drug candidates that appear to have an acceptable balance of benefits and risks typically proceed to testing in human clinical trials.
But there can be biological differences between these existing models and humans, so non-clinical lab tests can have significant limitations, explained Dr. Wu.
Currently, the first time humans are exposed to a new drug is during clinical trials, he said. We think it would be great if you could actually expose patients heart, brain, liver, or kidney cells to a drug in the lab, prior to clinical treatment, allowing researchers to determine whether the drug has any toxic effects.
Dr. Wu, a cardiologist by training, studies toxicities cancer drugs cause in heart cells. Human heart muscle cells (called cardiomyocytes), however, are hard to obtainrequiring risky heart surgery that may be of no direct benefit to the patientand are notoriously difficult to grow in the lab.
As an alternative, researchers have developed a method to produce heart cells from human induced pluripotent stem cells (hiPSCs). hiPSCs are created by genetically engineering normal human skin or blood cells to express four specific genes that induce them to act like stem cells. Chemical treatments can prompt hiPSCs to develop into mature cell types, such as heart muscle cells.
A large body of research has established that human adult stem cell-derived heart cells, which function and grow in cell culture, can be used as an initial model to screen drug compounds for toxic effects on the heart, said Myrtle Davis, Ph.D., chief of the Toxicology and Pharmacology Branch of NCIs Division of Cancer Treatment and Diagnosis, who was not involved in the studies.
For the Science Translational Medicine study, Dr. Wu and his colleagues set out to determine if a panel of human stem cell-derived heart cells could be used to evaluate the heart toxicity of 21 different FDA-approved TKIs.
They generated hiPSC-derived heart endothelial, fibroblast, and muscle cells from 13 volunteers: 11 healthy individuals and 2 people with kidney cancer who were being treated with a TKI. Using drug concentrations equivalent to what patients receive, the investigators next determined how lethal each TKI was to the heart cells.
They found that several TKIs were very lethal to endothelial, fibroblast, and heart muscle cells from all 13 individuals, while others were more benign.
Stem cell-derived heart muscle cells grown in a dish spontaneously contract as a beating heart does, so the researchers also analyzed the effects of TKIs on the cells beat rate, or contractility. They found that several TKIs altered the cells beat rate before they were killed by the drug treatment. If severe enough, an irregular heartbeat (called an arrhythmia), can disrupt normal heart function.
From these lethality and contractility experiments, the team developed a cardiac safety index, a 0-to-1 scale that identifies how toxic a TKI is to heart cells (with 0 being the most toxic). They then used the index to rank the 21 TKIs. The control treatment scored a 1, while a few TKIs that are labeled by the FDA with boxed warnings for severe heart toxicity scored close to 0.
Safety indices like this one can be very useful during drug discovery, said Dr. Davis, and the applicability of the index developed by Dr. Wu and his colleagues will become clear when they evaluate its performance with more compounds.
And for the safety index to be applicable to more patients, the panel of cells used to develop it would need to be gathered from a sufficiently representative population of people reflecting different ages, races/ethnicities, health statuses, and other characteristics, said Lori Minasian, M.D., deputy director of NCIs Division of Cancer Prevention, who was not involved in either study.
For example, the study did not include cells derived from patients with [pre-existing] cardiac disease, said Dr. Davis.
A Personalized Approach
In addition to their potential application during drug development, Dr. Wu believes that stem cell-derived heart cells could potentially be used to predict toxicity risk for individual patients. He and his colleagues explored this possibility in their Nature Medicine study.
Doxorubicin, used on its own or in combination with other drugs, is an effective treatment for breast cancer and several other types of cancer. Like TKIs, however, it is known to cause heart toxicities, such as arrhythmias and heart failure, in a small proportion of patients. But there has been no way to predict which patients will experience these side effects.
The researchers developed stem cell-derived heart cells from eight women with breast cancer who had been treated with doxorubicinhalf of whom experienced cardiotoxicity from the treatment and half who did not.
In several different lab tests, the heart cells from women who had experienced cardiotoxicity were more sensitive to doxorubicin than those from women who had not. More specifically, in heart cells from women who had experienced cardiotoxicity, doxorubicin treatment caused more severe irregularities in cell contractility, and even low concentrations of the drug killed the cells.
An Improved Model
While the stem cell-derived heart cell model may be an improvement over the current [drug testing] system, its not perfect, said Dr. Minasian. For example, the model does not capture contributions of other organs and cells to the toxic effects of a drug, she explained. The drug may be broken down in the liver, for instance, and side products (called metabolites) may also cause toxic effects.
In addition, the lab-grown stem cell-derived version of someones heart cells are not going to be exactly the same as the cells found in that persons heart, Dr. Wu noted. Nevertheless, they reflect the same genetics and they are pretty good at predicting drug response, he said.
Looking forward, Dr. Minasian said, figuring out how to best use this approach is going to take more work, but being able to better predict human response [to cancer drugs] is important.
The research teams next steps include conducting prospective studies to determine whether they can use a patients stem cell-derived heart cells to potentially predict if that person will develop heart toxicity before they actually receive cancer treatment.
This article has been republished frommaterialsprovided byNCI. Note: material may have been edited for length and content. For further information, please contact the cited source.
Reference
Sharma, A., Burridge, P. W., McKeithan, W. L., Serrano, R., Shukla, P., Sayed, N., ... & Matsa, E. (2017). High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Science translational medicine, 9(377), eaaf2584.
Excerpt from:
Measuring Heart Toxicity of Cancer Drugs | Technology Networks - Technology Networks
Swedish scientists successfully implant 3D-printed human cartilage cells in baby mice – TechCrunch
By Sykes24Tracey
In what could potentially serve as an importantmoment in the quest to 3D-print body parts, a team of scientists from Swedens Sahlgrenska Academy and Chalmers University of Technology have managed to successfully implant human cartilage cells in six-week-old baby mice.
The researchers created a gel composed of human cartilage cells, printed it through a CELLINK3D bioprinter and implanted the material inside the lab mice. Once implanted, the tissue began to grow and proliferate inside the animal, eventually vascularizing, with blood vessels growing inside the implanted material. After two months, the material began to more closely resemble human cartilage, which was further stimulated with the addition of stem cells.
The team worked with local plastic surgeons to implant the material, which could one day be used to create more natural implants for patients who have lost ears, noses or knees due to accidents or diseases like cancer.
There is no solution for missing ears, research lead professor Paul Gatenholm tells TechCrunch. You have plastic and silicone implants, which you need to put in with a titanium screw. Thats it. The surgical procedure is that you put in cartilage from a rib from the patient and carve. Its very painful and the outcome is very bad. If we can use cells from the nose and beef it up with stem cells from the patients bone marrow or fat, we will be able to print that full 3D structure.
Gatenholm adds, hopefully, It will have a great impact on healthcare for tissue regeneration and implementation. I think the first breakthrough will be of the skin and then the cartilage and then the bone. Beyond that, the technology could some day also be used for even more complex human parts like organs.
Gatenholm cites a paper from February of last yearin his discussion. In it, a team of researchers, including regenerative medicine professor Anthony Atala, detail how theyve used 3D bioprinting to construct bone and muscle using computer imaging to translat[e] the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations.
Similarly, 3D modeling in the form of CAD (computer-aided design) files can be used by the printer to create better anatomical pieces than plastic surgery modeling.
The process is still a ways from becoming a viable reality for future reconstructive surgery, including all of the regulatory approvals that come with implementing of this sort of invasive procedure. But the teams work marks a promising step in the process, which could some day extend beyond cartilage to other key human tissue.
Read the original post:
Swedish scientists successfully implant 3D-printed human cartilage cells in baby mice - TechCrunch
Scientists May Have Found A Way To Make Old Stem Cells Act … – Digital Trends
By NEVAGiles23
Get today's popular DigitalTrends articles in your inbox:
Why it matters to you
Nobody likes getting older. Reversing some of the bad aspects of the process helps us all age gracefully.
The suggestion that young blood may be the key toreversingsome of the negative aspects of aging sounds like the setup to a horror movie. In reality, however, itrefers to some groundbreaking work being carried out byscientists at the University of Ulm in Germany.
Theyve been examining the ways that old blood can be made young again, and they hypothesize that it might help fight some of the effects of aging.To achieve this, theyve discovereda protein capable of boosting blood stem cells, which prompts them to act like the stem cells of younger people.
More: Scientists may have discovered how to reverse the natural aging process
Older stem cells have several disadvantages, Dr. Hartmut Geiger, co-author of a paper describing the work, told Digital Trends. Theyresult in fewer red blood cells, and fewer of an important immune cell that fights infection. They also tend to produce more leukemia, which is a cancer of the blood. All of this is linked, at least in part, to the aging of stem cells. If you have younger stem cells, we think that we can reverse some of these effects.
Older stem cells tend to possess these negative characteristics thanks to the declining number of so-called mother stem cells in our bone marrow as we age. This decline triggers the effects Geiger describes.
In trials with mice, Geiger and his team discovered that older mice have lower levels of a protein called osteopontin. They decided to testthe effect of this protein on blood stem cells.
We took the stem cells from aged mice, incubated them with the osteopontin protein, and then gave them back, he continued.These blood stem cells, which had come from older animals, were found to have a lot of the features of stem cells coming from much younger animals in terms of function.
Its still early days for the research, but the suggestion that osteopontin could make stem cells behave in a more youthful way is certainly promising. The team is now developing a drug made up of osteopontin and a protein for activating it.
Hopefully human trials can follow in the not-too-distant future while were still around to benefit from them.
Follow this link:
Scientists May Have Found A Way To Make Old Stem Cells Act ... - Digital Trends
Man with 45% burns healed with stem cell treatment – ETHealthworld.com
By raymumme
Mumbai: A 45-year-old man -- suffering from 45 per cent burns due to a chemical spill at work -- has been healed with stem cell treatment, said the authorities at a hospital here on Friday.
Ram Naik (name changed) was brought to city-based StemRx Bioscience hospital after receiving first aid in another hospital. Nearly 45 per cent of his upper body was burned due to a chemical spill during work.
The impact of the burns led to a charred look on his face and body. Also, joint mobility due to the burns was reduced. The outer layer of the skin was affected, facial burns were of grade II level and in some instances grade III burns were also present, leading to deeper structures like the subcutaneous tissue also being affected.
According to the doctors, burn wound healing involves a series of complex processes, with healing time and scar tissue being the most important parameters that affect treatment outcomes. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients.
They said that stem cells have been recently applied in burn wounds to promote superior healing of the wounds. Not only have stem cells been shown to promote better and faster healing of the burn wounds, they are also capable of decreasing inflammation and prevent scar progression and fibrosis.
Therefore, the doctors decided to provide Naik stem cell treatment.
Regenerative Medicine researcher at Stemrx Bioscience hospital Pradeep Mahajan said that within two days, a notable improvement in his condition was observed and the swelling and charred appearance started reducing.
"Mild eyelid movements were noticed and on the third day the burns started drying on the face and he could open his mouth and eyes. Growth factors derived from platelets, cells, fibroblasts, collagen-based gel etc. was used during treatment. In addition, in areas with deep burns, sheets of PGLA coated with cells and growth factors were used," said Mahajan, adding that different medication and treatments were imparted and closed dressing was avoided.
"Blood transfusion and supplementary fluids were given intravenously to maintain systemic homeostasis," said Mahajan.
Stating that on 5th and 6th day following treatment, dry scales from the face and body started peeling off, the doctor's team also observed impressive changes such as new skin forming within a week of treatment with cells and growth factors.
By conventional modalities, it takes more than eight weeks for the patient to heal and many additional months for the patient to be able to regain joint and facial movements.
"By the 10th day of the treatment, dry scales completely peeled off and by the 14th day the patient had no tenderness or burning pain. Joint movements became free as well, Steady rate of progression of healthy skin formation is being noticed. Areas with deep burns are also healing at a rapid rate and I am confident that within a month we will accomplish thorough healing and the patient will be back to normal," Mahajan said.
Medical sciences say that such cases are challenging to manage considering the degree of impairment they result in due to prolonged healing period. Also, through conventional therapeutic modalities healing occurs with scar formation and results in contractures. Chances of systemic complications and infection are also high.
However according to the medical team, by using stem cells, the natural healing potential of the body is used, leading to reduction of healing time and promoting regeneration of affected tissues. This also reduces the mental trauma and financial burden that a patient goes through when under conventional management.
"Stem cell-based therapy has offered a novel and powerful strategy in almost every medical specialty including burns and wound management. Stem cells have proven to have tremendous potential in enhancing wound healing and facilitating skin regeneration," Mahajan said.
Go here to read the rest:
Man with 45% burns healed with stem cell treatment - ETHealthworld.com
Four Ways to Younger Skin Right Now – Forbes
By daniellenierenberg
Forbes | Four Ways to Younger Skin Right Now Forbes Her Hydrating and Plumping Serum No1 combats the environmental stressors that skin faces every day to detoxify and rejuvenate the face and subsequently enacting anti-aging properties. By using plant-stem cells, hyaluronic acid, marine snail peptides ... |
Read more here:
Four Ways to Younger Skin Right Now - Forbes