Thomas Jefferson University
Stem cells, with their ability to both stimulate endogenous repair mechanisms and replace dying neurons offer great promise as a potential stroke therapy. In a study conducted at Thomas Jefferson University, rat bone marrow stromal stem cells (BMSCs) were tracked after IV administration to rats with experimental stroke caused by middle cerebral artery occlusion (MCAO). In addition, the effects of BMSC treatment on blood cell composition, brain glia, and sensorimotor behavior were studied and compared to that which occurred spontaneously during the normal recovery process after stroke. It was found that the vast majority of radio labeled or fluorescently labeled BMSCs traveled to and remained in peripheral organs (lungs, spleen, liver) three days after IV injection in the MCAO rat. Once in the circulation, BMSCs also produced rapid alterations in host blood cell composition, increasing both neutrophil and total white blood cell count by six hours post injection.
In contrast, few injected BMSCs traveled to the brain and almost none endured there long term. Nonetheless, BMSC treatment produced dramatic changes in the number and activation of brain astroglia and microglia, particularly in the region of the infarct. These cellular changes were correlated with a marked improvement in performance on tests of sensory and motor function. It was concluded that the notable recovery in function observed after systemic administration of BMSCs to MCAO rats was likely due to the cellular changes in blood and/or brain cell number, activation state, and their cytokine/growth factor products.
University of Minnesota
Investigators in the Stem Cell Institute, University of Minnesota, in collaboration with the Departments of Neuroscience and Neurosurgery, are characterizing how neural stem cells, multipotent adult stem cells, or embryonic stem cells become mature neurons (nerve cells) and glial cells (non-nerve tissue of the brain and spinal cord). Studies employ innovative in vitro (in the lab) culture systems and state-of-the-art in vivo models (in the body or an organism) to determine the full potential of neural cells generated from stem cells.
University Hospitals Case Medical Center
A new national study looking at the safety and effectiveness of new medication developed from adult stem cells for the treatment of ischemic stroke opened at University Hospitals (UH) Case Medical Center. The Phase 2 study will use a cell therapy product called MultiStem. MultiStem is a proprietary medication made from a patented class of early adult stem cells called multipotent adult progenitor cells (MAPCs) that are obtained from the bone marrow. Hundreds of thousands to millions of doses can be made from the bone marrow cells of one donor. The cells do not come from the patient, so they can be made in advance, stored in the hospital, and be used off the shelf.
Unlike conventional drugs, it is believed that MultiStem therapy provides benefit in multiple ways when administered after an acute ischemic stroke. From the preclinical work, MultiStem cells appear to reduce the local inflammatory response and protect neurons in the brain while modulating the body’s general immune response and inflammation, which leads to additional damage to the brain in the days immediately following the stroke. This is an entirely new concept for how cell therapies may provide benefit following CNS injury and holds much potential. Results are anticipated to become known in the coming years.
Conclusion
Stem cell transplantation therapy for stroke holds great promise. However, many fundamental questions remain to be answered. Currently, many clinical trials in the United States are under way testing stem cell transplants for treating ischemic stroke. It is clear from early trials that many variables will need to be optimized. As more is learned in the labs about stem cells, especially the genetic aspect, the application of stem cells for ischemic stroke repair and regeneration is anticipated to bring positive results.
Atif Zafar
University of Iowa Hospitals and Clinics
Rakshanda Najam Siddiqi
Sind Medical College
Syed A. Quadri
Desert Regional Medical Center, Palm Springs
See Also: Blood Adult Stem Cell: Existing or Potential Regenerative Medicine Strategies; Clinical Trials Outside the United States: Stroke; University of Miami; University of Pittsburgh.
Further Readings
Bliss, Tonya, Raphael Guzman, Marcel Daadi, and Gary K. Steinberg. “Cell Transplantation Therapy for Stroke.” Stroke, v.38 (2007).
Goldmacher, G. V., R. Nasser, D. Y. Lee, S. Yigit, et al. “Tracking Transplanted Bone Marrow Stem Cells and Their Effects in the Rat MCAO Stroke Model.” PLoS ONE, v.8/3 (2013).
Lindvall, O. and Z. Kokaia. “Stem Cells for the Treatment of Neurological Disorders.” Nature, v.441/7097 (2006).
Meamar, Rokhsareh, Leila Dehghani, Majid Ghasemi, Fariborz Khorvash, and Vahid Shaygannejad. “Stem Cell Therapy in Stroke: A Review Literature.” International Journal of Preventive Medicine, v.4/Suppl 2 (May 2013).
“Stem Cell Research.” UTHealth. http://www.uth.edu/media/featured/stemcells.htm (Accessed May 2014).
Stone, Laura L., Andy Grande, and Walter C. Low. “Neural Repair and Neuroprotection With Stem Cells in Ischemic Stroke.” Brain Science, v.3 (2013).
“Stroke.” Stem Cell Network. http://www.stemcellnetwork.ca/index.php?page=stroke& (Accessed May 2014).
“Stroke Fact Sheet.” California Institute for Regenerative Medicine. http://www.cirm.ca.gov/our-progress/stroke-fact-sheet (Accessed May 2014).
University of Minnesota Stem Cell Institute. http://www.stemcell.umn.edu (Accessed May 2014).
Clinical Trials, U.S: Traumatic Brain Injury
Clinical Trials, U.S: Traumatic Brain Injury
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Clinical Trials, U.S: Traumatic Brain Injury
Each year, traumatic brain injuries (TBI) contribute to a substantial number of deaths and cases of permanent incapacity in children and adults from ages 1 to 44. Also known as intracranial injury, TBI occurs when an external force traumatically injures the brain, causing focal impact upon the head by a sudden acceleration/deceleration within the cranium or by a complex combination of both movement and sudden impact. It usually occurs as a bump, blow, or jolt to the head or as a penetrating head injury that disrupts the normal function of the brain. These injuries are mostly sustained in motor vehicle accidents, sports-related injuries, construction accidents, active-duty military action in war zones, or by simple falls on the playground, at work places, or in homes. The severity of a TBI may range from mild to severe.
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