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.
According to the Centers for Disease Control and Prevention (CDC), yearly there are at least 1.7 million traumatic brain injury (TBI) cases reported either as an isolated injury or along with other injuries, and they contribute to almost one-third (30.5 percent) of all injury-related deaths in the United States. Each year about 52,000 deaths occur from traumatic brain injury. Approximately 75 percent of these TBIs are concussions or other forms of mild TBI. Nearly half a million emergency room visits for traumatic brain injuries are made each year by children aged 0 to 14 years, though the highest rates of TBI-related hospitalizations and deaths occur in adults aged 75 years and older.
The degree of the neurologic deficits instigated by a TBI lesion is determined by two main factors, which are the primary mechanical insult and the secondary insult caused by inflammation, compression, and ischemia. The primary lesion is produced by the trauma itself and involves cellular death and tissue necrosis, independently of the biological factors. The mechanisms underlying secondary lesions comprise activation of inflammation, tissue ischemia, reperfusion deficits, edema, lipid peroxidation, calcium influx, and principally apoptosis. These secondary lesions establish the main target for the development of novel therapeutic approaches like stem cell therapy.
In human beings, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the hippocampus dentate gyrus (DG) are the two major stem cell niches in the adult brain. Stem cells have the capability to induce neuroprotection, inflammatory suppression, and neural repair, allowing reconstruction of totally damaged tissues or inhibiting partially damaged cells from progressing to cell death. However, the neurological improvements observed in preclinical and clinical trials have been based on results of neurological and behavioral tests, while the underlying mechanism of action of stem cells remains unknown.
Research into stem cells is just beginning in the United States and when it comes to brain injury, stem cell therapy is in its infancy. Not many trials are being carried out in the United States regarding the use of stem cells for TBI, but those that are under way have shown some promise.
In a Phase I clinical trial carried out at the University of Texas Health Science Center at Houston (UTHealth), bone marrow stem cells (BMSC) that were derived from the patient’s own bone marrow were safely used in pediatric patients with acute TBI. This clinical trial included 10 children aged 5 to 14 years with severe TBI and was carried out in partnership with Children’s Memorial Hermann Hospital, which is UTHealth’s primary children’s teaching hospital. All the children enrolled in this trial were treated acutely within 48 hours of their injury with their own stem cells collected from their bone marrow. These bone marrow stem cells were processed and administered intravenously to the children.
According to the data put forward by UTHealth, the acute harvesting of bone marrow and infusion of bone marrow mononuclear cells to acutely treat severe TBI in children is safe. As this was a Phase I trial to look at feasibility and safety of the method, this study did not evaluate the efficacy. Nonetheless, after six months of follow-up, all of the children had significant improvement, and seven of the 10 children revealed good outcome, displaying no or only mild disability.
In 2011, UTHealth began enrollment for the first Phase I safety study approved by the U.S. Food and Drug Administration (FDA) to investigate the use of a child’s own umbilical cord blood stem cells for traumatic brain injury in children. The study is being performed in conjunction with Children’s Memorial