Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem cell transplants improve recovery in animal models for stroke, cerebral palsy

10.04.2006
A single dose of adult donor stem cells given to animals that have neurological damage similar to that experienced by adults with a stroke or newborns with cerebral palsy can significantly enhance recovery from these types of injuries, researchers say.

Using a commonly utilized animal model for stroke, researchers administered a dose of 200,000-400,000 human stem cells into the brain of animals that had experienced significant loss of mobility and other functions. The stem cells used in the study were a recently discovered stem cell type, referred to as multipotent adult progenitor cells, or MAPCs.

Treated animals experienced at least 25 percent greater improvement in motor and neurological performance than controls, said Dr. Cesario V. Borlongan, neuroscientist at the Medical College of Georgia and the Veterans Affairs Medical Center in Augusta.

The findings are being presented April 7 during the 58th annual meeting of the American Academy of Neurology in San Diego.

In humans, the findings hopefully will translate to incremental but important recovery advances, said Dr. David Hess, adult stroke specialist, chair of the MCG Department of Neurology and a study co-author. “The single largest cause of disability among adults in ths U.S. is stroke,” said Dr. Hess. “It’s a huge public health problem in the world.” He hopes one day stem cell therapy, along with aggressive physical therapy and possibly tPA can work synergistically to reduce that disability.

“These are not going to be cures, but this level of recovery is significant, and could help get somebody out of a bed and into a wheelchair or out of a wheelchair to walking with a cane or from a cane to walking unassisted. If somebody can go from a wheelchair to a cane that is a big improvement, that is how we look at it,” Dr. Hess said.

Adult animals were tested across a range of standardized tasks both before and after undergoing the surgically induced stroke, and measurements were made of their performance. Following the stroke, both control animals and those that received a single injection of stem cells were evaluated for a period of up to 2 months. Improvements in stem cell treated animals included enhanced performance across the range of tests, which examined strength, balance, agility and fine motor skills, and also included greater recovery of injured tissue.

“A single dose of the cells produce robust behavioral recovery at an early period post-transplantation and the recovery was durable, lasting up to two months, which was the entire length of this study,” Dr. Borlongan said. “Furthermore, animals continued to show improvement over time.” In the newborn model of ischemic injury, enhanced recovery was found within two weeks.

Even though less than 1 percent of the transplanted cells were present two months later, animals receiving treatment developed new neurons, apparently formed from endogenous stem cells. “The mechanism that we are putting forward is these donor cells are secreting nourishing trophic factors that are helping the host brain cells survive and stimulating stem cells from the host to multiply,” Dr. Borlongan said.

To help mimic potential clinical scenarios for stroke victims, transplants were performed seven days after the initial injury. Currently, ischemic stroke patients may be treated with tPA, the only FDA-approved stroke treatment available, but must receive treatment within three hours from the time the stroke initially occurs. As a result, 95-97 percent of ischemic stroke victims never receive treatment with tPA.

In the adult stroke model, MCG researchers found giving stem cells increased the number of injured cells that survived in the area just outside the area of greatest damage, also referred to as the ischemic core, by 5-20 percent.

“Up to this point, all the treatment approaches, including transplantation and tPA, cannot get rid of that ischemic core,” Dr. Borlongan said. “But outside of that core there is a lining, what we call the penumbra, and that penumbra, if you do not treat it over time, becomes part of the core. We are showing, that even one week after a stroke, we are able to increase the number of cells surviving along that penumbra and that is how we feel it is producing significant recovery, by rescuing cells within the penumbra.”

Animals in the model of cerebral palsy, a condition caused by an ischemic injury similar to stroke but occurring before or during birth, also experienced at least a 25 percent improvement over controls. Rodent stem cells were used in this model, a larger percent of donated cells survived and within two weeks matured into neurons in the young, more pliable brains, Dr. Borlongan said. Also, close donor matching seemed unnecessary. Unmatched transplants, from the same species, and gentically identical transplants yielded essentially equal results.

Athersys, Inc., a Cleveland-based biopharmaceutical company pursuing cell therapy programs in cardiovascular disease, stroke, cancer and other diseases, funded the research in which previously frozen human or rodent multipotent adult progenitor cells, which the company calls MultiStem™, were thawed and injected directly into the brain.

Researchers believe that MultiStem™ cells are able to deliver a therapeutic benefit in multiple ways, for example by producing factors that limit tissue damage and stimulate repair, according to Dr. Gil Van Bokkelen, the company’s chairman and chief executive officer. In addition, MultiStem™ cells can safely mature into a broad range of cell types and can be produced on a large scale, something which should ease the move toward clinical studies and eventual clinical use. “Given the number of stroke victims each year, it would be a big step forward if a safe and effective stem cell therapy could be produced, conveniently stored, and efficiently delivered on a widespread basis. We believe that we can achieve that with MultiStem™,” commented Dr. Van Bokkelen.

In extensive animal testing, the mature stem cells have been shown to be safe, and do not form tumors or other abnormal tissue, a potential problem seen with embryonic stem cells. Furthermore, MultiStem™ cells generally do not require the close genetic matching between donor and recipient that is needed for a bone marrow or conventional stem cell transplant, according to company executives.

Another advantage is that use of immunosuppressive drugs does not appear to be required, in contrast to other types of stem cell treatment. Animals that received MultiStem™ without immunosuppression of any kind did just as well as animals that received MultiStem™ treatment along with daily doses of Cyclosporine A, a drug typically given to transplant recipients to prevent rejection. Such drugs can cause undesired side effects, and may be problematic if administered to patients for long periods of time. These results are consistent with those seen in other models, such as using MultiStem™ to treat damage caused by heart attacks, company officials say.

Although they have not specifically looked at whether stem cell therapy might be useful months after an ischemic event, MCG researchers and company scientists believe early therapy likely will be the most successful.

The researchers already are working with the Food and Drug Administration with the goal of beginning clinical trials within the next few years.

In preparation for potential clinical use, the researchers are pursuing transplants in larger animal models and studying how MultiStem™ cells work in living human brain tissue housed at the MCG Human Brain Bank, directed by Dr. Sergei Kirov.

“Number one is safety,” said Dr. Borlongan. “We are moving more aggressively into carrying this into the clinic but, at the same time, we are going to be very cautious and thorough in monitoring for any safety issues.”

Researchers also are working toward delivering the stem cells intravenously, an approach they believe will work because the cells naturally migrate to an injury site.

Other co-authors include Dr. James E. Carroll, chief of the Section of Pediatric Neurology; Dr. Lin Xu, MCG research scientist; Drs. Noriyuki Matsaukawa, Guolong Yu, Takao Yasuhara and Koichi Hara, MCG postdoctoral fellows; and Athersys scientists Robert W. Mays, and Robert J. Deans.

Toni Baker | EurekAlert!
Further information:
http://www.mcg.edu

More articles from Life Sciences:

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>