Tampa, Fla. (Dec. 1, 2010) The results of two studies published in the current issue of Cell Transplantation (19:9) using animal models of cerebral ischemia and ischemic stroke in rats may significantly impact the treatment of stroke in humans. One study found that administering bone marrow stromal stem cells (MSC) produced functional and structural recovery in stroke induced rats which coincided with activation of microglia and new blood vessel growth; a second study determined a therapeutic potential when vascular endothelial growth factor (VEGF) administration offered functional and structural protection from ischemic stroke damage;
Cell Transplantation is freely available on-line at http://www.cognizantcommunication.com/filecabinet/Cell/ct.htm .
Bone marrow stem cells administration promotes functional recovery
The study examining the effects of a systematic administration of either rat (allogenic) or human (xenogenic) bone marrow stem cells administered to laboratory rats one day after their simulated strokes found "significant recovery" of motor behavior on the first day. Early administration was found to be more effective than administration seven days after the simulated strokes.
"The timing of stem cell treatment was critical to the magnitude of the positive effects," said the study's lead author, Dr. Lorraine Iacovitti. "In the host animals we found profound changes and preserved brain structure along with long-lasting motor function improvement."
According to Dr. Iacovitti, there has been little research into just how stem cell transplantation modifies inflammatory and immune effects as well as promotes regenerative effects, such as blood vessel growth. They observed increased activation of microglia as well as modification of the circulating levels of cytokines and growth factors, including elevated VEGF and new blood vessel formation (angiogenesis) following transplantation.
"The mechanism through which MSCs achieve these remarkable effects remains elusive," said Dr. Iacovitti. "It is possible that activated glia cells (nonneuronal cells that perform a number of tasks in the brain) may play some role in the response, perhaps by partitioning off the infarcted region and limiting the spread of ischemic brain damage without inducing scar formation."
The researchers concluded that there was "little doubt" that the administration of stem cells can modify the cellular and molecular landscape of the brain and blood, limiting damage and protecting the stroke-injured brain.
Contact: Dr. Lorraine Iacovitti, Farber Institute for Neurosciences, Department of Neurology, Thomas Jefferson University, 900
Walnut St., Philadelphia, PA 19107, USA.
Tel: (215) 955-8118
Citation : Yang, M.; Wei, X.; Li, J.; Heinel, L. A.; Rosenwasser, R.; Iacovitti, L. Changes in Host Blood Factors and Brain Glia Accompanying the Functional Recovery after Systemic Administration of Bone Marrow Stem Cells in Ischemic Stroke Rats. Cell Transplant. 19(9):1073-1084; 2010
Injectable VEGF produces near complete neurological protection
A research team from InCytu, Inc. administered VEGF, a potent growth factor, via a sustained release hydrogel to examine the potential neuroprotective benefits in rats with simulated stroke.
"Although VEGF appears promising in animal models of stroke, its use has been hampered by a short half-life and poor penetration across the blood-brain barrier," said lead author Dr. Dwaine Emerich. "Our study was the first to demonstrate that implants of a sustained release hydrogel system could deliver VEGF directly to the site of infarction to prevent anatomical and behavioral consequences of transient cerebral ischemia."
According to Dr. Emerich, the VEGF-secreting gels "provided nearly complete" anatomical and neurological protection in the stroke-induced animals.
"This unique approach might have significant clinical potential for treating stroke and other acute CNS diseases in humans," he concluded.
Contact: Dr. Dwaine F. Emerich, InCytu, Inc. 701 George Washington Hgwy., Lincoln, Rhode Island 02865, USA.
Citation: Emerich, D. F.; Silva, E.; Ali, O.; Mooney, D.; Bell, W.; Yu, S. J.; Kaneko, Y.; Borlongan, C. V. Injectable VEGF Hydrogels Produce Near Complete Neurological and Anatomical Protection Following Cerebral Ischemia in Rats. Cell Transplant. 19(9):1063-1071; 2010.
"These studies show that modification of the ischemic environment by delivery of VEGF (and other cytokines) by stem cell or encapsulated hydrogel transplantation can afford significant functional and structural recovery after stroke", said Cell Transplantation section editor Dr. John Sladek, professor of neurology and pediatrics at the University of Colorado School of Medicine. "Thus, two potential and related ways of providing some recourse against the ravages of stroke are proposed."
|Contact: David Eve|
Cell Transplantation Center of Excellence for Aging and Brain Repair