The mystery of what controls the range of developmental clocks in mammals -- from 22 months for an elephant to 12 days for an opossum -- may lie in the strict time-keeping of pluripotent stem cells for each unique species.

Developmental clocks are of high importance to regenerative medicine, since many cell types take long periods to grow to maturity, limiting their usefulness to human therapies. The regenerative biology team at the Morgridge Institute for Research, led by stem cell pioneer and University of Wisconsin-Madison Professor James Thomson, is studying whether stem cell differentiation rates can be accelerated in the lab and made available to patients faster.

In a study published in February online editions of the journal Developmental Biology, Morgridge scientists tested the stringency of the developmental clock in human stem cells during neural differentiation. First, they closely compared the differentiation rates of the cells growing in dishes compared to the known growth rates of human cells in utero. Second, they grew the human stem cells within a mouse host, surrounded by factors -- such as blood, growth hormones and signaling molecules -- endemic to a species that grows much more rapidly than humans.

In both cases -- lab dish and different species -- the cells did not waver from their innate timetable for development, without regard to environmental changes.

"What we found remarkable was this very intrinsic process within cells," says lead author Chris Barry, a Morgridge assistant scientist. "They have self-coding clocks that do not require outside stimulus from the mother or the uterus or even neighboring cells to know their pace of development."

While the study suggests that cellular timing is a stubborn process, the Thomson lab is exploring a variety of follow-up studies on potential factors that could help cells alter their pace, Barry says.

One aspect of the study that's immediately valuable across biology is the realization that how stem cells behave in the dish aligns almost precisely with what happens in nature.

"The promising thing is that we can take species of stem cells, put them in tissue culture, and more confidently believe that events we're seeing are probably happening in the wild as well," Barry says. "That is potentially great news for studying embryology in general, understanding what's going on in the womb, and disease modeling for when things can go wrong."

It also opens up potential avenues in embryology that would have been inconceivable otherwise -- for example, using stem cells to accurately study the embryology of whales and other species with much longer (or shorter) gestation rates than humans.

In order to accurately compare development timing across species with wildly different gestation rates -- nine months compared to three weeks -- the team used an algorithm called dynamic time warping, originally developed for speech pattern recognition. This algorithm will stretch or compress the time frame of one species to match up with similar gene expression patterns in the other. Using this process, they identified more than 3,000 genes that regulate more rapidly in mice and found none that regulate faster in human cells.

The impact of solving the cell timing puzzle could be enormous, Barry says. For example, cells of the central nervous system take months to develop to a functional state, far too long to make them therapeutically practical. If scientists can shorten that timing to weeks, cells could potentially be grown from individual patients that could counteract grave diseases such as Parkinson's, multiple sclerosis, Alzheimer's disease, Huntington's disease and spinal cord injuries.

"If it turns out these clocks are universal across different cell types," says Barry, "you are looking at broad-spectrum impact across the body."

A video highlighting Barry's work can be seen at https://vimeo.com/183526442.

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Materials provided by University of Wisconsin-Madison. Original written by Brian Mattmiller. Note: Content may be edited for style and length.

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Stem cells fiercely abide by innate developmental timing, study ... - Science Daily

SAN CARLOS, Calif., March 1, 2017 /PRNewswire/ --Natera (NTRA), a leader in genetic testing, today announced the upcoming launch of Evercord; a new offering being made commercially available in the second quarter of 2017 that enables expectant parents to collect, store and potentially retrieve their newborn's cord blood and tissue for therapeutic use in transplantation and regenerative medicine applications. Natera aspires to build a different type of national cord blood company, by combining best-in-class cord blood cryopreservation with the company's ability to provide timely information about genetic disease risk; potentially expanding families' stem cell treatment options in the future. Natera will offer Evercord through its leading direct sales channel in the United States.

The Market Potential of Cord Blood Stem Cells Newborn stem cells sourced from umbilical cord blood are known to contain hematopoietic stem cells (HSCs) that can potentially differentiate and regenerate healthy blood and immune systems. Unfortunately, out of the roughly four million births each year in the United States, more than 95% of the cord blood from those births is currently discarded as waste;1 highlighting a significant opportunity both for families who could benefit from cord blood, and for Natera, as it enters the cord blood and tissue banking market. Published data also suggests that one in three people in the United States, or 128million people, could potentially benefit from regenerative medicine applications which, if proven effective, expands the possible therapeutic use of cord blood stem cells.2 More than 300 studies are currently underway, including clinical trials focused on current and new cord blood stem cell therapies in regenerative medicine.3 These trials hold promise for a growing list of conditions, including Alzheimers disease, cerebral palsy, diabetes (Type I/II), spinal cord injury, cartilage and bone repair, and heart defects. More than 30,000 cord blood stem cell treatments have been conducted worldwide and Natera's prenatal tests, including its carrier test, Horizon, currently screen for 35 of the nearly 80 diseases where cord blood stem cell treatment has been administered. Considering the research advances in stem cells and regenerative medicine, it is anticipated that number will, more than likely, continue to grow.

Introducing EvercordThe launch of Evercord is part of a partnership with Bloodworks Northwest, one of the oldest and most reputable public umbilical cord blood banks in the country. Evercord's service will offer expectant families the opportunity to bank their baby's umbilical cord blood and tissue for potential medical use by the child or related family member. Under the terms of the agreement between Natera and Bloodworks, Bloodworks will perform processing and testing services on cord blood samples submitted by Evercord customers and will cryo-preserve the banked cord blood and tissue at its Seattle, Washington-based best-in-class cord blood cryopreservation storage facility. The companies also plan to build a new facility in anticipation of future growth.

The relationship offers several other competitive advantages. Evercord leverages Bloodworks' 20 years of experience processing and banking cord blood; the lab has a strong track record of successfully releasing nearly 1,000 cord blood samples for transplant, more than other leading private cord blood banks.

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Once Evercord is commercially launched, it will expand Natera's existing portfolio of women's reproductive health products, further diversifying Natera's revenue base and adding a traditionally high yield business into its product mix. Evercord will also be well positioned to immediately take advantage of Natera's well-established commercial capabilities, including: patient and healthcare provider digital services through Natera's Patient Portal and Natera Connect, and a specialized salesforce that already calls on the nation's busiest obstetrics and gynecology offices and fertility centers.

"At Natera, we believe adding cord blood and tissue banking to our product offerings is a natural extension of our commitment to family health and beyond," said Matt Rabinowitz, CEO and founder of Natera. "Evercord builds on our excellence as a genetic testing company and our mission to transform the diagnosis and management of genetic diseases. Cord blood stem cells have demonstrated regenerative capabilities that medicine is just beginning to learn how to harness; offering a unique opportunity to potentially generate complete genetic information on a human being at the moment of birth. Many of the genetic diseases that cord blood treats today are also conditions that our tests screen for, which could enable us to offer a far more extensive service offering in the future than those offered by leading 'storage-only' cord blood banks today."

About Bloodworks Northwest's Public Cord Blood ProgramBloodworks Northwest partners with hospitals across the region to recover and store umbilical cord blood from new mothers -- an important source of stem cells for use in cancer treatment, metabolic or immune system disorders, and research. Bloodworks Northwest created the first and only public umbilical cord blood bank in the Northwest of the United States and has program partnerships with 15 hospitals across Washington, Oregon and Hawaii providing nearly 50 units per month to the national cord bloodregistry.

About NateraNatera is a genetic testing company that develops and commercializes non-invasive methods for analyzing DNA. The mission of the company is to transform the diagnosis and management of genetic disease. In pursuit of that mission, Natera operates a CAP-accredited laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, CA, and it currently offers a host of proprietary genetic testing services primarily to OB/GYN physicians and fertility centers, as well as to genetic laboratories through its cloud-based Constellation software system.

Product offerings include the Spectrum pre-implantation genetic test for embryo selection during IVF; the Anora miscarriage test to understand the genetic causes of a pregnancy loss; the Horizon carrier test to detect inherited mutations; the Panorama non-invasive prenatal test (NIPT) to identify common chromosomal anomalies in a fetus as early as nine weeks of gestation; and Evercord, a cord blood and tissue banking service offered at birth to expectant parents.

Each test described has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test.

These tests have not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although FDA does not currently clear or approve laboratory-developed tests in the U.S., certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.

Natera is also applying its unique technologies to develop non-invasive screening and diagnostic tools for earlier detection and improved treatment of cancer. These tests have not been cleared or approved by the U.S. Food and Drug Administration.

Forward-looking statementsThis release contains forward-looking statements. All statements other than statements of historical facts contained in this press release are forward-looking statements. Any forward-looking statements contained in this press release are based upon Natera's historical performance and its current plans, estimates, and expectations, and are not a representation that such plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release.

Subsequent events may cause these expectations to change, and Natera disclaims any obligation to update the forward-looking statements for any reason after the date of this press release. These forward-looking statements are subject to a number of known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to our efforts to develop and commercialize new product offerings, our ability to successfully increase demand for and grow revenues for our product offerings, whether the results of clinical studies will support the use of our product offerings, whether cord blood or cord tissue will be found to be effective in treating additional conditions, our expectations of the reliability, accuracy and performance of our screening tests, or of the benefits of our screening tests and product offerings to patients, providers and payers.

Additional risks and uncertainties are discussed in greater detail in the sections entitled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in Natera's Form 10-Q for the quarter ended September 30, 2016. Further information on potential risks that could affect actual results will be included in other filings Natera makes with the SEC from time to time. These documents are available for free on the company's website at http://www.natera.com under the Investor Relations section, and on the SEC's website at http://www.sec.gov.

Contacts:Natera, Inc. Mike Brophy, Chief Financial Officer, 650-249-9091 x1471 mbrophy@natera.com Laura Zobkiw, Corporate and Media Relations, 650-249-9091 x1649 Lzobkiw@natera.com

1https://parentsguidecordblood.org/en/cord-blood-infographic (February 2017). 2 Harris, D., & Rogers, I. (2007). Umbilical Cord Blood: A Unique Source of Pluripotent Stem Cells for Regenerative Medicine.Current Stem Cell Research & Therapy,2(4), 301-309. doi:10.2174/157488807782793790; http://www.mdpi.com/2227-9059/2/1/50/htm 3https://clinicaltrials.gov/ct2/results?term=Umbilical+AND+Stem+Cells (February 2017).

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Natera, Inc. Announces Launch of Evercord Cord Blood and Tissue Banking Service - Yahoo Finance

Former football player raising money for stem cell treatment ... Lexington Herald Leader A Danville native who hopes to be able to walk again is raising money for life-changing treatments. and more »

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Former football player raising money for stem cell treatment ... - Lexington Herald Leader

Medical tourism is alive and well in places all over the world. Thailand, Mexico and Colombia are just some of the destinations where people travel in order to get affordable health care. While finances are the main concern of medical tourists, another reason to make the trip is for services that arent provided in a travelers local city or country. Stem Cells are still a controversial topic in many countries and while research is being conducted, people who might benefit from the treatments may not be able to locate a qualified provider. Why travel so far just for stem cell treatment? Well.

They May Be Able To Cure Cancer

Cancer is one of the most prevalent diseases out there without a cure. With so many people falling ill to this disease, the need for a cure is more important than ever. Stem cell studies are being conducted and researchers have found that stem cell therapy can be used to add healthy cells into the system to suppress the disease while stimulating the growth of new and healthy marrow. Hodgkins Lymphoma, breast cancer and ovarian cancer may benefit the most from these treatments.

They Could Be Capable of Treating Blood Disease

According to NSI Stem Cell, stem cell therapy may be able to provide the body with regenerative and healthy blood cells to combat blood disease. With healthy blood cells in the system, diseases like Sickle Cell Anemia, Fanconi Anemia and Thalassemia could be effectively treated.

They Have The Ability To Treat Injuries and Wounds

By increasing blood vessels and improving blood supply, stem cells could treat both chronic and acute wounds, especially in older patients who dont heal as quickly. Specifically, stem cell therapy could help treat surface wounds, limb gangrene and the replacement of jawbone.

Research Is Being Done On a Huge Variety of Treatment Potential

Stem cells are constantly undergoing research to uncover their potential when it comes to medical treatments. Some of the treatments being explored include:

-Auto-immune Disease: These cells may be able to repair and regenerate damaged tissue for people suffering from Rheumatoid Arthritis, Buergers Disease, and Systemic Lupus.

-Neurodegeneration: They could help with diseases such as MS and Parkinsons.

-Brain & Spinal Cord Injuries: The cells could reduce inflammation and help to form healthy, new tissue.

-Heart Conditions: Stem cells are being utilized to create new blood vessels, reverse tissue loss and regenerate heart muscle tissue.

-Tooth & Hair Replacement: They can help grow thinning hair and replace missing teeth.

-Vision Loss: Retinal cells are being injected into the eyes to improve vision.

-Pancreatic Cells: Healthy Beta Cells in the pancreas are being produced by stem cells. These therapies would help diabetic patients and allow them to decrease their dependence on insulin.

-Orthopedics: Stem cells can be utilized to treat arthritis and ligament/tendon injuries.

-HIV/Aids: Researchers are looking into using stem cells to produce an immune system that is resistant to disease.

The Cost of Treatment Will Vary But Can Be Affordable

While it may seem that the cost of stem cell therapy would be extremely high, the truth is that it varies. It all depends on the treatment necessary but the range could be from $1,000 to $100,000. In the future, insurance companies may even cover costs for some treatments.

Stem Cells Come From Multiple Sources

Stem cells come from a whole variety of places including bone marrow, adipose tissue, blood and umbilical cords. In the case of extraction from adipose tissue, they can be harvested and then put back in a patient after only a couple of days. All of the procedures to acquire the stem cells can be done with willing participants and donors.

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Why People Are Traveling For Stem Cell Treatment | The Huffington ... - Huffington Post

NEW DELHI: Private banking of umbilical cord blood is a big business running parallel to childbirth in big hospitals, but is it worth the cost? While companies offering the facility for a few thousand rupees claim it can be used to treat conditions ranging from cerebral palsy to diabetes, health experts and doctors disagree. They say stem cell transplantation for treatment is limited to hereditary or genetic conditions, specifically blood disorders.

In both cases, umbilical cord blood cannot be used to save the donor since it will have the same genetic abnormalities. Its usage for treating the donor's siblings, or other family members, is also rare, as the HLA (a protein) has to match and weight-to-cord-blood ratio with the recipient has to be just right.

The limitations notwithstanding, expecting mothers are flooded with offers to preserve the cord blood. Patients complain that most private hospitals and boutiques for childbirth allow marketing agents from stem cell banking facilities to freely solicit them. "I was inundated with calls from stem cell companies trying to convince me to go for umbilical cord preservation. On each visit to the hospital, representatives from these companies hound you," said Nutan Verma, who is expecting twins.

Geeta Sharma said she went through multiple presentations from executives of stem cell banking companies while waiting in hospital to deliver her baby. "They offered free genetic testing, lifelong storage and other benefits. I chose one of them offering to preserve umbilical cord for 21 years at Rs 50,000. The company representative told me that the contract can be renewed on expiry," she said.

Geeta Jotwani, deputy director general of Indian Council of Medical Research (ICMR), told TOI that private companies offering to preserve umbilical cord blood must be strictly regulated. "Soliciting of patients by selling fake hopes is wrong. There is no evidence of stem cell use from umbilical cord presently, except in blood disorders. Only those having family members with these disorders should store it," she said.

Jotwani said ICMR was working on guidelines for stem cell banking which would be made public soon. "Many private banks are storing cord tissue, dental pulp, menstrual blood and adipose tissue as well for which there is no scientific evidence of any use in treatment as yet," she added.

Dr S P Yadav, paediatric hematologist at Medanta Medicity, Gurgaon, said private stem cell banking companies claimed that umbilical cord blood could be used to treat spinal cord injury, cerebral palsy and even diabetes, though there is no such proven research. "Currently, only five medical conditions can be treated through cord blood stem cell transplant blood cancer, bone marrow failure, thalassaemia and sickle cell anaemia, immune system deficiency since birth and inborn errors of metabolism," he said. "The chances of cord blood being used in the family or by the donor are 0.01%. Still, if somebody wants to preserve it, they should be allowed to. The problem is when poor or middle class families are lured into doing so with false claims about preserved blood being a panacea for all diseases," said Yadav.

On average, private banking of stem cells derived from cord blood costs Rs 50,000 to Rs 70,000. Banks claim to freeze the cells in liquid nitrogen so that it can be used up to 20 years from the date of preservation.

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Umbilical cord blood: Cord blood: Big business, small benefits ... - Times of India

GERMANTOWN, Md., Feb. 22, 2017 (GLOBE NEWSWIRE) -- Neuralstem, Inc. (CUR), a biopharmaceutical company focused on the development of central nervous system therapies based on its neural stem cell technology, today announced that U.S. Patent No. 9572807 was issued by the United States Patent and Trademark Office (USPTO) for NSI-189, the lead compound in Neuralstem's neurogenic small molecule program in development for the treatment of major depressive disorder. US 9,572,807 has claims to protocols for using NSI-189 and related compounds for treatment of major depressive disorder. Counterparts have been filed in Australia, Canada, Europe, Japan, Singapore and South Korea. These patents will expire in June 2035.

The new patent adds to the portfolio of over 20 U.S. and 120 foreign issued and pending patents that are owned or licensed to Neuralstem in the field of regenerative medicine. This includes U.S. Patent No. 9,540,611, issued on January 10, 2017 by the USPTO, covering the treatment of neurodegenerative diseases using NSI-566, the companys proprietary neural stem cell therapy candidate.

We are excited to be bringing forward therapeutic options that could make a tremendous difference in the lives of those who suffer from nervous system disorders and conditions, said Rich Daly, Chairman and CEO, Neuralstem. We will continue to aggressively establish a broad portfolio of intellectual property to protect our research and development efforts.

About Neuralstem

Neuralstems patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are being developed as potential therapies for multiple central nervous system diseases and conditions.

Neuralstems technology enables the generation of small molecule compounds by screening hippocampal stem cell lines with its proprietary systematic chemical screening process. The screening process has led to the discovery and patenting of molecules that Neuralstem believes may stimulate the brains capacity to generate new neurons, potentially reversing pathophysiologies associated with certain central nervous system (CNS) conditions.

The company has completed Phase 1a and 1b trials evaluating NSI-189, a novel neurogenic small molecule product candidate, for the treatment of major depressive disorder or MDD, and is currently conducting a Phase 2 efficacy study for MDD.

Neuralstems stem cell therapy product candidate, NSI-566, is a spinal cord-derived neural stem cell line. Neuralstem is currently evaluating NSI-566 in three indications: stroke, chronic spinal cord injury (cSCI), and Amyotrophic Lateral Sclerosis (ALS).

Neuralstem is conducting a Phase 1 safety study for the treatment of paralysis from chronic motor stroke at the BaYi Brain Hospital in Beijing, China. In addition, NSI-566 is being evaluated in a Phase 1 safety study to treat paralysis due to chronic spinal cord injury as well as a Phase 1 and Phase 2a risk escalation, safety trials for ALS. Patients from all three indications are currently in long-term observational follow-up periods to continue to monitor safety and possible therapeutic benefits.

Cautionary Statement Regarding Forward Looking Information

This news release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements relate to future, not past, events and may often be identified by words such as expect, anticipate, intend, plan, believe, seek or will. Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Specific risks and uncertainties that could cause our actual results to differ materially from those expressed in our forward-looking statements include risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstems periodic reports, including the Annual Report on Form 10-K for the year ended December 31, 2015, and Form 10-Q for the nine months ended September 30, 2016, filed with the Securities and Exchange Commission (SEC), and in other reports filed with the SEC. We do not assume any obligation to update any forward-looking statements.

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Neuralstem Announces Issuance of US Patent Covering NSI-189 - Yahoo Finance

Severely hyperbranched vascular network surrounding the spinal cord (red dotted box) of zebrafish embryo blood vessels in white.

A team of researchers at Karlsruhe Institute of Technology (KIT) shake at the foundations of a dogma of cell biology. By detailed series of experiments, they proved that blood vessel growth is modulated by neurons and not, as assumed so far, through a control mechanism of the vessel cells among each other. The results are groundbreaking for research into and treatment of vascular diseases, tumors, and neurodegenerative diseases. The study will be published in the journal Nature Communications.

Our work is pure basic research, Professor Ferdinand le Noble of KITs Zoological Institute says, but provides a completely new perspective on how blood vessels grow, branch out, or are inhibited in their growth. For decades, researchers have been looking for ways to promote or impede the formation of new blood vessels. Whereas heart attack and stroke patients would profit from new arteries, cancer patients would benefit from tumor starving by putting a stop to ingrowing blood vessels.

The key figures in the newly discovered extremely finely balanced process are signaling molecules: the brake on growth soluble FMS-like tyrosine kinase-1, referred to as 1sFlt1, and the vascular endothelial growth factor, referred to as VEGF. Even though, so far, it has been largely unknown how VEGF is regulated by the body, inhibition of this growth factor has been applied for years already in the treatment of cancer patients and of certain eye diseases. The therapy, however, is successful only in part of the patients and has several undesired side effects.

So far, research assumed the blood vessels to more or less regulate their own growth, explains le Noble. In case of oxygen deficiency, he points out, tissue, among others, releases the growth factor VEGF, thus attracting the blood vessels carrying VEGF receptors on their surfaces. We wanted to know how this blood vessel growth is regulated at the time of a creatures birth. The team around le Noble hence studied the continuous growth of nerve tracts and circulatory vessels in zebrafish model organisms. The eggs of zebrafish are transparent and develop outside of the mothers body, allowing researchers to watch and observe the development of organs or even individual cells without injuring the growing animal.

By means of fluorescent dyes, postgraduate Raphael Wild in a first step documented colonization of neuronal stem cells and subsequent vascular budding in the vertebral canal of zebrafish. To understand the exact process, the team started a detailed biochemical and genetic analysis.

The researchers proved that at different development stages, the nerve cells of the spinal cord produce more or less sFlt1 and VEGF and, in this way, modulate the development of blood vessels. At the early development stage, neuronal sFlt1 brakes blood vessel growth by binding and inactivating the growth factor VEGF. In the spinal cord, this creates an environment poor in oxygen, which is essential to the early development of the neuronal stem cells. With increasing nerve cell differentiation, concentration of the soluble sFlt1 decreases continuously, and the brake on vascular growth is loosened because more active VEGF is now available. Subsequently, blood vessels grow into the young spinal cord to provide it with oxygen and nutrients.

In addition, Raphael Wild and his colleague Alina Klems show that the concentration of the growth factor is crucial as regards the density of the developing blood vessel network. Whereas, when the brake sFlt1 in nerve cells was switched off completely, a dense network of blood vessels formed which even grew into the vertebral canal, the growth of blood vessels was suppressed when sFIt1 was increased. Even small variations in substance concentration thus led to severe vascular developmental disorders.

Since vascular cells also have own forms of sFlt1 and VEGF, the question arose as to whether blood vessel growth may, to a certain degree, regulate itself. To find out, the researchers applied the still young and extremely elegant CRISPR/Cas method: Whereas there was no effect when sFlt1 was switched off only in vascular cells, an intensive growth of blood vessels was observed when the production of sFlt1 was switched off in the nerve cells only.

From the results we conclude that by a fine modulation of sFlt1 and VEGF, nerve cells very dynamically regulate the density of their blood vessel network according to requirements or according to the respective development stage, le Noble points out. The previous assumption that growing blood vessel cells control the succeeding vascular cells is a cell biology dogma whose foundations are being shaken.

Please note: The content above may have been edited to ensure it is in keeping with Technology Networks style and length guidelines.

References:Wild, R., Klems, A., Takamiya, M., Hayashi, Y., Strhle, U., Ando, K., Mochizuki, N., van Impel, A., Schulte-Merker, S., Krueger, J., Preau, L. and le Noble, F. (2017) Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization, Nature Communications, 8, p. 13991. doi: 10.1038/ncomms13991.

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Neurons Signal Spinal Cord Vascularisation - Technology Networks (press release) (registration) (blog)

The Register's editorial 5:32 p.m. CT Feb. 20, 2017

A tray of vials containing cerebral spinal fluid in Baltimore used to analyze both adult and fetal tissue in cancer research.(Photo: AP)

Among the threats to scientific advances are politicians who do not understand science. Unfortunately, too many of these politicians land jobs in the Iowa Legislature. They send a message this state is the last place a medical researcher should locate.

In 2002, lawmakers with an unfounded fear of scientists cloning babies passed a bill banning the creation of stem cells through a process called somatic cell nuclear transfer. Researchers useembryos, left over from in vitro fertilization, that would otherwise be discarded. After the vote banning the process, lawmakers were crying, hugging and carrying on about how life begins at conception.

Their emotion was pathetically misguided, as there was nothing pro-life about the measure. In fact, the law jeopardized life-saving research. It also prompted a cell biologist at the University of Iowa to pack up, move to Illinois and take her team and millions of federal dollars for cancer research with her.

Now here we go again. Lawmakers who apparently lack anunderstanding of laboratory research and the history of medical advancementsare pushing Senate File 52 in yet another effort to meddle in the work of real scientists. The bill, recently approved by a GOP-led Senate subcommittee,would ban acquiring, providing, receiving, otherwise transferring or using fetal tissue in this state. Fetal tissue, extracted during legal, voluntary abortions, can be discarded or used in medical research.

Lawmakers apparently would rather it be discarded. Committee chair Sen. Jake Chapman, R-Adel, said he didn't want to hinder research, but we also need to understand there is a moral responsibility, as well, to ensure that baby body parts arent being sold.

The same way no one was cloning babies in Iowa more than a decade ago, no one is selling "baby parts" today.

But inflammatory rhetoric is what people resortto when they don't want to acknowledge facts. Federal law already prohibits profiting from selling fetal tissue. Planned Parenthood of the Heartland says its Iowa affiliate does not even donate it. If the bill becomes law, anyone using fetal tissue namely researchers could land in the slammer for up to 10 years.

The Iowa Board of Regents registered opposition to the legislation, along with lobbyists representing the medical industry, churches and others. The board, which oversees state universities, requested an exemption that would allow research on certain fetal cells and proposed language to enable medical donations and permit the diagnosis of diseases.

Lawmakers did not immediately amend the bill, even thoughUI has been one of dozens of institutions across the country that has used fetal tissue in medical research. In recent years, the National Eye Institute provided the school more than $1 million for glaucoma research that used the tissue, according to data compiled by the Associated Press in 2015.

Fetal tissue has been successfully used for decades in medical research. It was critical in creating a vaccine for polio, a disease that crippled, paralyzed and sometimes killed its victims. Scientistsinfected fetal kidney cellsto produce mass quantities of the virus that were collected, purified and used for inoculations. They won a Nobel Prize for Medicine in 1954.

Research using human fetal cells shows promise in treatments for spinal cord injuries, eye disease, strokes and Parkinson's disease. But some Iowa lawmakers appear uninterested in saving and improvinglives.They are, however, interested in catering to theanti-abortion crowd with a bill that would not prevent a single abortion.

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Editorial: Fetal tissue bill is anti-life, anti-science - DesMoinesRegister.com

Asterias Biotherapeutics (AST) continues to generate excitement and buzz around its stem cell treatment for catastrophic spinal cord injury (SCI). I wrote about this historic event back in September. Thats when the company first released results about this transformative medical breakthrough.

Asterias has now released follow-up data. This was gathered at six and nine months after six quadriplegics received treatment. All six continue to show improvement in motor function and sensation. This is truly wonderful news for those with SCI.

There are also broader medical implications and these should be of great interest to investors.

The difference between this stem cell therapy and traditional drug therapies is huge. Drug therapies have specific and mechanistic impacts. But stem cells derived from embryonic cells work a different way. They draw on the massive DNA databanks in their nuclei. They then use these genetic programs to interact with their surroundings and repair damaged structures.

The Asterias oligodendrocyte progenitor cells were derived from a single unused embryo (from an IVF procedure in the late 1990s). Such embryos are often discarded. But this one was donated to create an unlimited number of therapeutic cells. Both the Bush and Obama Administrations approved the cell line.

When injected into the site of a spinal cord injury, these cells create healthy new spinal cord structures. They restore myelin sheaths (which are like an insulating material on nerves) and repair the lesions caused by injury. They send chemical signals that stimulate the growth of nerve cells. They also generate blood vessels that deliver oxygen and nutrients (and clear out toxic substances).

In works of science fiction, you may have read about nanobots. These are theoretical nanomachines that can fix profound biological damage. But the truth is that we all have this type of device in our bodies at the embryonic stage of development. Each uses the complex repair systems that can be found in the human genome.

These are the cells (AST-OPC1) that were given to patients in the SCI trial. The result is that patients who could not breathe on their own can now perform complex physical tasks. We have seen them lift weights, text, and type 35 words a minute and they continue to improve.

Most people assume this therapy must be the most modern of biotechnologies. In truth, its quite old in modern scientific terms. Dr. Michael West oversaw the creation of this therapy over two decades ago as Gerons chief science officer.

When that company stumbled, he brought the clinical trial and Gerons IP into BioTime (*see disclosure below) as Asterias Biotherapeutics. When I spoke to Asterias CEO Steve Cartt, his excitement was palpable. Heres why.

Each year, about 17,000 people experience the kind of spinal cord injuries targeted by the current trial. AST-OPC1 would be the only approved treatment for this condition.

Cartt is now considering plans to extend clinical trials to those who have suffered less serious spinal cord injuries. This means the patient population for AST-OPC1 cells would expand a great deal.

These cells might also be used to treat other neurological diseases. Multiple sclerosis, for example, also involves the deterioration of the myelin nerve sheath. But this is just the tip of iceberg for pluripotent stem cell therapies. Many of our worst diseases can be addressed by these biological nanobots.

If spinal cords can be repaired, so can the connective tissue deterioration that leads to arthritis and joint failures. Im convinced we will see simple injections of stem cells to repair hip, knee, and other joints in the future.

BioTime has also done extensive research into stem cell therapies for heart muscle and cardiovascular repair. In fact, Dr. West has converted some of my cells to embryonic status. He then engineered them to become my heart muscle cells. There have been animal studies as well. The results indicate that these types of cells will repair the damage done by heart attacks.

Next up, though, is blindness. A BioTime subsidiary in Israel, Cell Cure Neurosciences, is in a phase 1/2a trial to treat dry age-related macular degeneration (dry-AMD). Israeli government grants have helped fund this project.

Based on animal trials, it seems that the companys retinal pigment epithelial cells will be successful in treating the leading cause of adult blindness. Dry-AMD is an attractive target because there is no effective treatment. From what Ive learned, I think that these cells will treat the wet form of macular degeneration and other causes of blindness as well.

This is the real importance of the Asterias SCI trial. Right now, were seeing the proof of concept for a biotechnology that will disrupt the entire healthcare market. I've written about this extensively in Tech Digest (subscribe here for free).

This change will happen sooner than you think. Japan has already revised its Pharmaceutical Affairs Act to speed up the approval of stem cell therapies. And on the home front, several of President Trump's candidates for FDA chief have endorsed similar reforms.

(*Disclosure: The editors or principals of Mauldin Economics have a position in BioTime (BTX) which has significant ownership of Asterias stock. They have no plans to sell their position at this time. There is an ethics policy in place that specifies subscribers must receive advance notice should the editors or principals intend to sell.)

This weekly newsletter by biotech expert Patrick Cox highlights research that is much more advanced than most people know, and the profit potential for investors is vast. Read about the latest breakthroughsfrom new, non-invasive cancer treatments to age-reversing nutraceuticals and vaccines that kill any virusas well as the innovative companies that work on them. Get Tech Digest free in your inbox every Monday.

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A Breakthrough in Stem Cell Treatment? - Equities.com

Stem cell therapy treatment gives new lease of life to 5-year-old Jamshedpur February 17, 2017 , by Desk 1

Ranchi : Till very recently, it was believed that brain damage is irreversible. However, now with emerging research; we understand that it is possible to repair the damaged brain tissue using cell therapy.

Again, today there are still many people in India who have not preserved their stem cells through cord blood banks. For all those patients, who have lost their hopes in finding a new treatment for neurological related disorders, adult stem cell therapy offers a new hope for such kind of patients.

Dr Alok Sharma, Director, NeuroGen Brain and Spine Institute, Professor and Head of Neurosurgery, LTMG Hospital & LTM Medical College, Sion said Stem cell therapy is emerging as one of the newer treatment options for conditions like Autism, Cerebral Palsy, Mental retardation, Muscular Dytrophy, Spinal Cord Injury, Paralysis, Brain Stroke, Cerebellar Ataxia and Other Neurological Disorders. This treatment has the potential to repair the damaged neural tissue at molecular, structural and functional level.

Dr. NandiniGokulchandran, Deputy Director, Neurogen Brain and Spine Institute saidStem Cell Therapy (SCT) done at NeuroGen Brain and Spine Institute is a very simple and safe procedure. Stem Cells are taken from patients own bone marrow with the help of one needle and are injected back in their Spinal Fluid after processing.

Since they are taken from the patients own body there is no rejection, no side effects, hence making SCT a completely safe procedure.

Today, we are presenting a case study of Ranchi based 5 yrs old Master Dhairya Singh. He is a known case of brain damage due to lack of oxygen but not during birth. Dhairya was born in a normal manner, cried immediately after birth also his birth weight was appropriate.

There were no immediate post-natal complications reported. Dhariya was a normal child till the age of one and half years old. Then one day he suffered from an episode of pneumonia for which he was hospitalized for 6 days.

Last updated:Friday, February 17, 2017

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Stem cell therapy treatment gives new lease of life to 5-year-old - Avenue Mail

Belleville News-Democrat

A baby's first act, saving a life Belleville News-Democrat Currently, stem cells are being researched to try to find cures or ways to treat autism, spinal cord injury, stroke recovery and Alzheimer's disease. Doll-Pollard said that it is incredibly important for the family to weigh these options before a ...

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A baby's first act, saving a life - Belleville News-Democrat

Back to Browse Journals Journal of Neurorestoratology Volume 5

Zhijian Cheng, Xijing He

Department of Orthopedics, The Second Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi, Peoples Republic of China

Abstract: Spinal cord injury (SCI) is a traumatic event that involves not just an acute physical injury but also inflammation-driven secondary injury. Macrophages play a very important role in secondary injury. The effects of macrophages on tissue damage and repair after SCI are related to macrophage polarization. Stem cell transplantation has been studied as a promising treatment for SCI. Recently, increasing evidence shows that stem cells, including mesenchymal stem, neural stem/progenitor, and embryonic stem cells, have an anti-inflammatory capacity and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation. In this review, we will discuss the role of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.

Keywords: stem cells, macrophages, spinal cord injury, polarization

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Anti-inflammatory effect of stem cells against spinal cord injury via | JN - Dove Medical Press

Science Daily

Your brain's got rhythm: Synthetic brain mimics Science Daily Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem ... and more »

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Your brain's got rhythm: Synthetic brain mimics - Science Daily

February 14, 2017 Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem cells and termed a 'circuitoid.' Credit: Salk Institute

Not everyone is Fred Astaire or Michael Jackson, but even those of us who seem to have two left feet have got rhythmin our brains. From breathing to walking to chewing, our days are filled with repetitive actions that depend on the rhythmic firing of neurons. Yet the neural circuitry underpinning such seemingly ordinary behaviors is not fully understood, even though better insights could lead to new therapies for disorders such as Parkinson's disease, ALS and autism.

Recently, neuroscientists at the Salk Institute used stem cells to generate diverse networks of self-contained spinal cord systems in a dish, dubbed circuitoids, to study this rhythmic pattern in neurons. The work, which appears online in the February 14, 2017, issue of eLife, reveals that some of the circuitoidswith no external promptingexhibited spontaneous, coordinated rhythmic activity of the kind known to drive repetitive movements.

"It's still very difficult to contemplate how large groups of neurons with literally billions if not trillions of connections take information and process it," says the work's senior author, Salk Professor Samuel Pfaff, who is also a Howard Hughes Medical Institute investigator and holds the Benjamin H. Lewis Chair. "But we think that developing this kind of simple circuitry in a dish will allow us to extract some of the principles of how real brain circuits operate. With that basic information maybe we can begin to understand how things go awry in disease."

Nerve cells in your brain and spinal cord connect to one another much like electronic circuits. And just as electronic circuits consist of many components, the nervous system contains a dizzying array of neurons, often resulting in networks with many hundreds of thousands of cells. To model these complex neural circuits, the Pfaff lab prompted embryonic stem cells from mice to grow into clusters of spinal cord neurons, which they named circuitoids. Each circuitoid typically contained 50,000 cells in clumps just large enough to see with the naked eye, and with different ratios of neuronal subtypes.

With molecular tools, the researchers tagged four key subtypes of both excitatory (promoting an electrical signal) and inhibitory (stopping an electrical signal) neurons vital to movement, called V1, V2a, V3 and motor neurons. Observing the cells in the circuitoids in real time using high-tech microscopy, the team discovered that circuitoids composed only of V2a or V3 excitatory neurons or excitatory motor neurons (which control muscles) spontaneously fired rhythmically, but that circuitoids comprising only inhibitory neurons did not. Interestingly, adding inhibitory neurons to V3 excitatory circuitoids sped up the firing rate, while adding them to motor circuitoids caused the neurons to form sub-networks, smaller independent circuits of neural activity within a circuitoid.

"These results suggest that varying the ratios of excitatory to inhibitory neurons within networks may be a way that real brains create complex but flexible circuits to govern rhythmic activity," says Pfaff. "Circuitoids can reveal the foundation for complex neural controls that lead to much more elaborate types of behaviors as we move through our world in a seamless kind of way."

Because these circuitoids contain neurons that are actively functioning as an interconnected network to produce patterned firing, Pfaff believes that they will more closely model a normal aspect of the brain than other kinds of cell culture systems. Aside from more accurately studying disease processes that affect circuitry, the new technique also suggests a mechanism by which dysfunctional brain activity could be treated by altering the ratios of cell types in circuits.

Explore further: Scientists discover new mechanism of how brain networks form

More information: Matthew J Sternfeld et al, Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells, eLife (2017). DOI: 10.7554/eLife.21540

Journal reference: eLife

Provided by: Salk Institute

Scientists have discovered that networks of inhibitory brain cells or neurons develop through a mechanism opposite to the one followed by excitatory networks. Excitatory neurons sculpt and refine maps of the external world ...

A new study presented in the journal Nature could change the view of the role of motor neurons. Motor neurons, which extend from the spinal cord to muscles and other organs, have always been considered passive recipients ...

When you're taking a walk around the block, your body is mostly on autopilotyou don't have to consciously think about alternating which leg you step with or which muscles it takes to lift a foot and put it back down. That's ...

We humans walk with our feet. This is true, but not entirely. Walking, as part of locomotion, is a coordinated whole-body movement that involves both the arms and legs. Researchers at the Biozentrum of the University of Basel ...

Dr. Kevin Collins carefully places a petri dish with what looks like a blotch of yellowish slime under a microscope. Magnified, the slime comes alive as hundreds of translucent worms, known as Caenorhabditis elegans, slither ...

Imagine yourself sitting in a noisy caf trying to read. To focus on the book at hand, you need to ignore the surrounding chatter and clattering of cups, with your brain filtering out the irrelevant stimuli coming through ...

Not everyone is Fred Astaire or Michael Jackson, but even those of us who seem to have two left feet have got rhythmin our brains. From breathing to walking to chewing, our days are filled with repetitive actions that ...

Whether we're navigating a route to work or browsing produce at the grocery store, our brains are constantly making decisions about movement: Should I cross the street now or at the intersection? Should I reach for the red ...

Pain is a signal of actual or potential damage to the body, so it is natural to think of it as a localized sensation: knee pain in the knee, back pain in the back and so on.

Researchers from the University of Toronto, Canada, have discovered a reason why we often struggle to remember the smaller details of past experiences.

The feel-good brain chemical dopamine appears to play a role in the development of a healthy bond between a mother and baby, a new study suggests.

Proteins are the building blocks of all cells. They are made from messenger RNA (mRNA) molecules, which are copied from DNA in the nuclei of cells. All cells, including brain cells regulate the amount and kind of proteins ...

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Your brain's got rhythm - Medical Xpress

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Transparency Market Research, in a report titled Stem Cells Market Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 2018, states that the global stem cells market is projected to witness remarkable growth from 2012 to 2018, fueled by increasing government support, unmet medical needs, rising stem cell banking services, and growing medical tourism. Driven by these factors, the global stem cells market is anticipated to expand at a 24.20% CAGR during the forecast period, rising from a value of US$26.2 bn in 2013 to US$119.5 bn by 2018.

Browse the full Stem Cells Market (Adult, Human Embryonic , Induced Pluripotent, Rat-Neural, Umbilical Cord, Cell Production, Cell Acquisition, Expansion, Sub-Culture) Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 2018 report at http://www.transparencymarketresearch.com/stem-cells-market.html

Rise in disposable income in emerging economies, the increasing prevalence of neurodegenerative disorders, development of the contract research industry, and replacement of animal tissue in drug discovery are also anticipated to contribute towards the overall growth of the stem cells market.By product, the stem cells market is categorized into adult stem cells, induced pluripotent stem cells, very small embryonic-like stem cells, human embryonic stem cells, and rat neural stem cells. Adult stem cells, which dominated the overall market in 2011, include mesenchymal stem cells, dental stem cells, neuronal stem cells, hematopoietic stem cells, and umbilical cord stem cells.

On the basis of technology, the stem cells market is segmented into stem cell acquisition, production, cryopreservation, and expansion and sub-culture. Stem cell acquisition is the largest as well as the most rapidly developing technological segment and includes bone marrow harvesting, umbilical cord blood, and apheresis. The segment of stem cell production includes cloning, isolation, in-vitro fertilization, and cell culture.

On the basis of application, the stem cells market is bifurcated into regenerative medicine and drug discovery and development. Regenerative medicine, which holds the larger share in the stem cells market, covers major disciplines such as orthopedics, hematology, wound care, diabetes, incontinence, neurology, oncology, cardiovascular and myocardial infarction, spinal cord injuries, and liver disorders.

Geographically, the global stem cells market is divided into Europe, Asia Pacific, North America, and Rest of the World. North America dominates the overall market, followed by Europe owing to increased prevalence of neurological and cardiac disorders, state initiatives and provision of grants from several organizations, development of innovative therapies, strong research activities, and effective marketing solutions. The Asia Pacific stem cells market is anticipated to witness impressive growth over the next two years thanks to rapidly growing contract research outsourcing and booming medical tourism.

The leading companies profiled in the stem cells market report are Osiris Therapeutics, Advanced Cell Technology, Cellartis AB, Bioheart, Cellular Engineering Technologies, Biotime Inc., Cytori Therapeutics Inc., Angel Biotechnology, Stemcelltechnologies Inc., California Stem Cell Inc., Brainstorm Cell Therapeutics, and Celgene Corporation Inc. These players are analyzed based on aspects such as company and financial overview, product portfolio, business strategies, and recent developments.

Global Stem Cells Market, By Product

Adult Stem Cells Hematopoietic Stem Cells Mesenchymal Stem Cells Neuronal Stem Cells Dental Stem Cells Umbilical Cord Stem Cells Human Embryonic Stem Cells Induced Pluripotent Stem Cells Rat Neural Stem Cells Very Small Embryonic-Like Stem Cells Global Stem Cells Market, By Technology

Stem Cell Acquisition Bone Marrow Harvest for Stem Cells Apheresis for Stem Cells Umbilical Cord Blood Stem Cell Production Therapeutic Cloning for Stem Cells Stem Cells Production By In Vitro Fertilization Stem Cell Isolation Stem Cell Culture Stem Cell Cryopreservation Stem Cells Expansion and Sub-Culture Global Stem Cells Market, By Application

Regenerative Medicine Neurology Orthopedics Oncology Hematology Cardiovascular and Myocardial Infarction Injuries Diabetes Liver Disorders Incontinence Others Drug Discovery and Development Global Stem Cells Market, By Geography

North America Asia Pacific Europe Rest of the World

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Transparency Market Research (TMR) is a global market intelligence company providing business information reports and services. The companys exclusive blend of quantitative forecasting and trend analysis provides forward-looking insight for thousands of decision makers. TMRs experienced team of analysts, researchers, and consultants use proprietary data sources and various tools and techniques to gather and analyze information.

TMRs data repository is continuously updated and revised by a team of research experts so that it always reflects the latest trends and information. With extensive research and analysis capabilities, Transparency Market Research employs rigorous primary and secondary research techniques to develop distinctive data sets and research material for business reports.

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Stem Cells Market Share, Size, Growth & Forecast 2018 Illuminated by New Report - Satellite PR News (press release)

After a spinal cord injury, many of the nerve fibers at the injury site lose their insulating layer of myelin. As a result, the fibers are no longer able to properly transmit signals between the brain and the spinal cord contributing to paralysis. Unfortunately, the spinal cord lacks the ability to restore these lost myelin-forming cells after trauma.

Tissue engineering in the spinal cord involves the implantation of scaffold material to guide cell placement and foster cell development. These scaffolds can also be used to deliver stem cells at the site of injury and maximize their regenerative potential.

When the spinal cord is damagedeither accidentally (car accidents, falls) or as the result of a disease (multiple sclerosis, infections, tumors, severe forms of spinal bifida, etc.)it can result in the loss of sensation and mobility and even in complete paralysis.

For publications on spinal cord injuries, please click here.

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Spinal Cord Injury and Stem Cell Therapy

Forbes

This Breakthrough In Biotech Has Enormous Investment Potential Forbes Asterias Biotherapeutics (AST) continues to generate excitement and buzz around its stem cell treatment for catastrophic spinal cord injury (SCI). I wrote about this historic event back in September. That's when the company first released results about ...

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This Breakthrough In Biotech Has Enormous Investment Potential - Forbes

Greg Iger/Keck Medicine of USC

Kristopher Boesen, who broke his neck in a car accident, regained the ability to move his arms and hands after his spinal cord was injected with stem cells.

Two years after having a stroke at 31, Sonia Olea Coontz remained partially paralysed on her right side. She could barely move her arm, had slurred speech and needed a wheelchair to get around. In 2013, Coontz enrolled in a small clinical trial. The day after a doctor injected stem cells around the site of her stroke, she was able to lift her arm up over her head and speak clearly. Now she no longer uses a wheelchair and, at 36, is pregnant with her first child.

Coontz is one of stem-cell therapy's miracle patients, says Gary Steinberg, chair of neurosurgery at Stanford School of Medicine in California, and Coontz's doctor. Conventional wisdom said that her response was impossible: the neural circuits damaged by the stroke were dead. Most neuroscientists believed that the window for functional recovery extends to only six months after the injury.

Stem-cell therapies have shown great promise in the repair of brain and spinal injuries in animals. But animal models often behave differently from humans nervous-system injuries in rats, for example, heal more readily than they do in people. Clinical trial results have been mixed. Interesting signals from small trials have faded away in larger ones. There are plenty of unknowns: which stem cells are the right ones to use, what the cells are doing when they work and how soon after an injury they can be used.

The field is still young. Stem cells are poorly understood, and so is what happens after a spinal-cord injury or stroke. Yet, there are success stories, such as Coontz's, which seem to show that therapy using the right sort of stem cell can lead to functional improvements when tried in the right patients and at the right time following an injury. Researchers are fired up to determine whether stem-cell therapies can help people who are paralysed to regain some speech and motor control and if so, what exactly is going on.

Neurologists seeking functional restoration are up against the limited ability of the human central nervous system to heal. The biology of the brain and spinal cord seems to work against neuroregeneration, possibly because overgrowth of nerves could lead to faulty connections in the finely patterned architecture of the brain and spine, says Mark Tuszynski, a neurologist at the University of California, San Diego. Local chemical signals in the central nervous system tamp down growth. Over time, scarring develops, which prevents the injury from spreading, but also keeps cells from entering the site.

It's really hard to fix the biology, says Charles Yu Liu, a neurosurgeon and director of the University of Southern California Neurorestoration Center in Los Angeles. Stem cells seem to promise a workaround.

So far, neural regeneration cell therapy has had only anecdotal success, leaving investors and patients disappointed. In people with Parkinson's disease, for example, neurosurgeons replaced dead and dying dopamine-producing neurons with fetal neurons. Although initial results were promising, in larger studies, patients reported involuntary movements. Another effort tried treating people who'd had a stroke with cells derived from tumours; the results were mixed, and researchers were uneasy about the cells' cancerous source.

In recent years, researchers have had success with stem cells coaxed to develop into particular cell types, such as neural support cells. Tuszynski has showed how well stem cells can work at least, in animal models1. His group implanted neural stem cells derived from human fetal tissue into rats with severe spinal-cord injuries. Seven weeks later, the cells had bridged the gap where the spinal cord had been cut and the animals were able to walk again. The cells used in the study were manufactured by Neuralstem of Rockville, Maryland. The group has shown that other kinds of stem cell, including those derived from adult tissue, also work. Tuszynski has seen similar results in a rat spinal-cord-injury model, using neural stem cells made from the tissues of a healthy 86-year-old volunteer2.

Mark Tuszynski/Ken Kadoya/Ref. 3

Regeneration of axons (red) beyond implanted neural progenitor cells (green) in a rat with a spinal injury.

But animal studies are also making it clear that simply regrowing the connective wiring of the nervous system to bridge damaged areas is not enough, says Zhigang He, who studies neural repair at the Harvard Stem Cell Institute in Cambridge, Massachusetts. No matter what the animal model is, he says, the axons don't always grow into the right places. It's not enough to have a nerve, that nerve must become part of a functional circuit.

There is growing evidence that besides becoming replacement nerves, stem cells perform other functions they also seem to generate a supportive milieu that may encourage the natural recovery process or prevent further damage after an injury. Many types of neural stem cell secrete a mix of molecules that unlock suppressed growth pathways in nerves. Earlier this year, Tuszynski reported that any sort of spinal-cord stem cell, whether derived from adult tissues or embryos, from humans, rats or mice, could trigger native neural regeneration in rats3. But his success in rats has not yet translated into clinical trials. More work is needed, Tuszynski says, to determine which type of cell will work best for which particular injury.

For people who have had a stroke or spinal-cord injury, physical therapy is currently the best hope for recovery in the weeks and months after the injury. The brain is plastic and can co-opt other circuits and pathways to compensate for damage and to restore function. Once the inflammation ebbs and the brain adjusts, people can start to regain function. But the window of opportunity is short. Most people don't make functional gains after six months.

That timeline is why the remarkable recovery enjoyed by Coontz and other patients with chronic stroke in the same clinical trial is so surprising, says Steinberg. This changes our whole notion of recovery, he says. There were 18 people in the trial Coontz took part in, and all were treated using stem cells manufactured by SanBio of Mountain View, California. The company's cells are bone-marrow-derived mesenchymal stem cells. The cells are treated with a DNA fragment that is transiently expressed in them, and causes changes in their protein-expression patterns. In animal studies, these cells promote the migration and growth of native neural stem cells, among other effects.

The trial, which was designed to look at safety as well as efficacy, recruited patients after an ischaemic stroke. During this kind of stroke, a clot cuts off the blood supply to part of the brain, causing significant damage. Patients in the trial had all had ischaemic strokes deep in the brain 736 months earlier past the 6-month window for significant recovery. Each patient was injected with either 2.5 million, 5 million or 10 million of SanBio's cells4. Steinberg has followed participants for 24 months; an interim study at 12 months reported that most patients showed functional improvements. Some, like Coontz, achieved almost complete recovery.

What is not clear, however, is what the stem-cell injections do in the brain. In animal studies, the SanBio cells do not turn into neurons, but seem to send supporting signals to native cells in the brain. Indeed, preclinical research shows that the cells do not integrate into the brain most die after 12 months. Instead, the cells seem to secrete growth factors that encourage the formation of new neurons and blood vessels, and foster connections called synapses between neurons. And in rats, the nerve-cell connections that extended from one side of the brain to the other, as well as into the spinal cord, lasted, even though the injected cells did not4.

But these mechanisms are not sufficient to explain Coontz's overnight restoration of function, says Steinberg. He is entertaining several hypotheses, including that the needle used to deliver the cells may have had some effect. One week after treatment, we saw abnormalities in the premotor cortex that went away after one month, he says. The size of these microlesions was strongly correlated with recovery at 12 months. A similar effect can happen when electrodes are implanted in the brains of people with Parkinson's, although this deep-brain stimulation quietens tremors for only a short time. The people who'd had a stroke had a lasting recovery, suggesting that both the needle and the stem cells may have played a part.

The SanBio trial was small, and did not have a placebo control; the company is now recruiting for a larger phase II trial. Of the 156 participants that will be recruited, two-thirds will have cells injected the others will have a sham surgery. Even the trial surgeons, including Steinberg, will not know who is getting which treatment. The main outcome measure will be whether patients' motor-skill scores improve on a test called the Fugl-Meyer Motor scale six months after treatment. Participants will be monitored for at least 12 months, and will also be evaluated with tests that look for changes in gait and dexterity. Meanwhile, Steinberg plans to study microlesions in animal models of stroke to determine whether they do have a role in recovery.

An ongoing clinical trial evaluating escalating doses of neural stem cells in patients with acute spinal-cord injuries is also looking promising. Asterias Biotherapeutics of Fremont, California, coaxes the cells to develop into progenitors of oligodendrocytes, a type of support cell that's found in the brain and spinal cord and that creates a protective insulation for neuronal axons.

The trial tests the safety and efficacy of administering these cells to people with recent cervical, or neck-level, spinal-cord injury. Interim results for patients who had received the two lower doses were presented at the International Spinal Cord Society meeting in September. After 90 days, 4 patients who received 10 million cells showed improved motor function; a fifth patient had not reached the 90-day mark yet. At one year, the three patients receiving a lower dose of two million cells showed measurable improvement in motor skills.

These cells were initially developed by Geron, a biotechnology company that has since moved away from regenerative medicine. Before spinning out Asterias in 2013, Geron had run a safety trial of the cells in people with a chronic lower-back injury. No issues were identified, and the US Food and Drug Administration agreed to let the company test the cells in patients who'd been recently injured. Asterias focused the current trial on patients with cervical injuries because these are closer to the brain, so new nerve cells have a shorter distance to grow to gain functional improvements. People with severe cervical spine injuries are typically paralysed below the level of the damage. The company's hope is to restore arm and hand function for people with such injuries, potentially making a tremendous difference to a person's independence and quality of life.

Asterias seems to have realized this hope in at least one patient who received one of the higher doses. Kristopher Boesen, who is 21, has had a dramatic recovery. In March, Boesen's car fishtailed in a rainstorm; he hit a telephone pole and broke his neck. About a month later, Boesen was still paralysed below the injury, and his neurological improvements seemed to have plateaued. His doctors at a trauma centre in Bakersfield, California, were in touch with Liu, who is an investigator in the Asterias trial. As soon as he was stable, Boesen travelled to Los Angeles to join the trial.

Liu injected Boesen's spinal cord with Asterias's cells in April. Two days later, Boesen started to move his hands, and in the summer, he regained the ability to move the toes on one foot.

Asterias Biotherapeutics

A surgeon prepares to inject stem cells to treat a spinal injury as part of Asterias's clinical trial.

Liu is excited about Boesen's response. He was looking at being quadriplegic, and now he's able to write, lift some weights with his hands, and use his phone, says Liu. For somebody to improve like this is highly unusual I want to be jumping out of my shoes. But Liu cautions that this is still a small trial, and that Boesen's response is just one anecdotal report. Until the results are borne out in a large, placebo-controlled clinical trial, Liu will remain earthbound.

The trial is currently recruiting between 5 and 8 patients for another cohort that will receive a doubled dose of 20 million cells. As the trial goes on, Asterias hopes to find clues about the underlying mechanism. We're looking at changes in the anatomy of the injury, says the company's chief scientific officer, Jane Lebkowski. She says that there is some evidence that axons have traversed the injury site in patients who have recovered function. Preclinical work suggests that the cells might be sending growth-encouraging chemical signals to the native tissue. And, as support cells, the astrocytes may also be preventing more neurons from dying in the aftermath of the acute spinal injury.

Not all clinical trials have performed so well. The SanBio and Asterias results are positive signals in a sea of negative or mixed trials. For example, StemCells of Newark, California, terminated its phase II trial of stem cells for the treatment of spinal-cord injury in May, and shortly afterwards announced that it will restructure its business. The company declined to comment for this article.

Physicians such as Liu and Steinberg temper their public enthusiasm about stem-cell therapies, so as not to give false hope to desperate patients. People with paralysing injuries or those who have a neurodegenerative disease are easy marks for unscrupulous stem-cell clinics, whose therapies are not only unproven, but also come with risks.

Patients say, 'Go ahead, doc, you can't make me any worse,' says Keith Tansey, a neurologist and researcher at the Methodist Rehabilitation Center in Jackson, Mississippi, and president-elect of the American Spinal Injury Association. Unfortunately, that is not the case. Cell therapies given at a clinic, outside the context of a clinical trial, can lead to chronic pain, take away what little function a patient has left and render a patient ineligible for future studies, says Tansey. He has seen the consequences in his clinical practice. I treated a kid who had two different tumours in his spinal cord from two different individuals' cells, he says.

Many unanswered questions remain about whether stem cells can heal the central nervous system in people, and how they might do it. Researchers also don't know what cells are the best to use. Is it enough for them to grow into supportive cells that send friendly growth signals, or is it better that they grow into replacement neurons? The answer is likely to differ depending on the site and nature of the disease or injury. If the stem cells are producing supportive factors that encourage growth and repair, it might be possible, says He, to discern what these are and give them directly to patients. But biologists are not yet close to deciphering the recipe for such a cocktail.

Every time we get an experiment done we realize it's more complex than we thought it would be.

Tansey agrees that there are many unknowns and these seem to be multiplying. Every time we get an experiment done we realize it's more complex than we thought it would be, he says. Tansey thinks that the best way to resolve such uncertainties is with carefully regulated clinical trials. Rat models will only tell us so much the human nervous system is much larger and is wired differently. If stem cells help patients such as Coontz and Boesen to regain their speech and give them greater independence without adverse effects, then it makes sense to continue, he says, even without knowing all the details of how they work.

Until these positive, but small, results are replicated in larger, controlled clinical trials, neurologists are containing their optimism. I'd like to hear of any clinical trial that has more than an anecdotal benefit, says Tansey. And Liu is anticipating the day when he won't need to control his elation. In a few years, perhaps there will be a genuine opportunity to jump for joy.

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A New Delhi clinic that has claimed to help paralyzed Canadians walk again by injecting them with stem cells now says it can use the same treatment to make children with Down syndrome almost near normal.

Nutech Mediworld says it has treated up to 16 newborns, toddlers and older children with Down syndrome. According to its medical director, Geeta Shroff, we have seen that patients actually start improving clinically they become almost at par for their age.

Canadian experts say the bold claim risks raising false expectations and public confusion, much like the now-discredited Liberation therapy for multiple sclerosis, and that its playing off the over-hyped belief stem cells have the potential to cure almost anything.

Its also the latest controversy over stem cell tourism, and the growing number of clinics worldwide marketing pricey, unregulated and unproven treatments.

Nutech Mediworld charges US$5,000 to $6,000 per week for its stem cell-based therapies. The clinic says it has treated such incurable conditions as spinal cord injury and cerebral palsy. Around 20 Canadians have sought treatment at the clinic for paralyzing spinal cord injuries, spending upwards of $US48,000 each. Shroff says some of her patients have regained the ability to walk with walkers.

More recently, she began working with Down syndrome, one of the most common chromosomal disorders worldwide.

Most cases are caused by a random error in cell division. The child ends up with three copies of chromosome 21, instead of the usual two.

That extra copy causes abnormal neuronal development and changes in the central nervous system, Shroff says, leading to persistent developmental delays.

Human embryonic stem cells injected into a childs muscles and bloodstreamcan regenerate and repair that damaged brain, she says. They also work at the genetic level, she claims.

In a single case published last year, Shroff reported treating a two-month-old baby boy in September 2014 diagnosed with Down syndrome at birth. The infant had delayed milestones, lack of speech, subnormal understanding and subnormal motor skills, she wrote.

After two stem cell therapy sessions, the baby started babbling and crawling, she reported. He had improved muscle tone. He was social and was able to recognize near ones.

The child became almost as near normal as possible cognitively

The child became almost as near normal as possible cognitively, Shroff told the Post in an interview. Today, hes talking; hes walking. He was at par with normal children on analysis.

The former infertility specialist uses embryonic stem cells developed from a single fertilized egg donated by an IVF patient 17 years ago. According to Shroff, We have witnessed no adverse events at all.

The Down syndrome treatments, reported by New Scientist, have raised skepticism and alarm. Its not at all clear what cells shes actually putting in patients, says renowned developmental biologist Janet Rossant, senior scientist at the Hospital for Sick Children Research Institute in Toronto.

By just putting them into the bloodstream theres no way to imagine they could contribute to the right tissues.

Embryonic stem cells can also form teratomas benign tumours and masses composed of lung cells, tufts of hair, teeth, bone and other tissues.

The gold standard for any therapy would be a clinical trial comparing treated with untreated children and vetted through proper regulatory systems that clearly she is not going through, Rossant says.

The Ottawa Hospitals Dr. Duncan Stewart, who is leading the first trial in the world of a genetically enhanced stem cell therapy for heart attack, says theres a remote chance embryonic stem cells could help with Down syndrome. But its a stretch. The injected cells would also likely be rejected and die off with days, he believes. If the cells are disappearing within days, how are they working?

This is a very vulnerable population Theyre very vulnerable to people who are selling hope and have no basis for it

This is a very vulnerable population, Stewart adds. Theyre very vulnerable to people who are selling hope and have no basis for it.

But stem cells have taken on almost mystical appeal.

Theyve become a pop culture phenomenon, says healthy policy expert Timothy Caulfield, of the University of Alberta. The field itself is guilty of making breathless announcements about breakthroughs and cutting edge, he says. And people can market that kind of language.

This kind of nonsense doesnt help.

Email: jskirkey@postmedia.com | Twitter:

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From Down syndrome to 'near normal'? New Delhi clinic makes stem cell claims that worry experts - National Post

For many people suffering from disabling conditions, such as Parkinsons disease, spinal injury and paralysis, heart disease, and even cancer, announcements in the press around breakthroughs in stem cell research undoubtedly bring hope.

Keeping the balance between hope and hype is a difficult one, particularly when there are vulnerable and suffering people relying on the hope medical research offers. As Australian of the Year, Emeritus Professor Alan Mackay-Sim, stated in his acceptance speech, there are now many clinical trials being performed in Australia and around the globe, to determine whether the delivery of certain types of cells, including some grown from stem cells, into the spinal column can allow patients with spinal cord injury to regain function.

For these individuals, even a small gain of functionis a major advance. However, as yet there is no stem cell silver bullet.

And stem cells that have shown promise can also cause complications. It was also reported a paraplegic woman developed a growth in her spine many years after an unsuccessful spinal stem cell treatmentHence, more research to test these and other types of cells in well-run clinical trials is required to move from anecdote to safe and effective therapies.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:The future of stem cells: tackling hype versus hope

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Hype versus hope: Deciphering news about stem cell breakthroughs - Genetic Literacy Project