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Friday, November 23, 2007

Scientists have tested the capabilities of cellular therapy for ischemic stroke treatment



Stem Cell Injection Protects Against Nerve Cell Death After Stroke, Study Suggest
Scientists have tested the capabilities of cellular therapy for ischemic stroke treatment on rats. It has turned out that intravenous transplantation of mesenchymal stem cells restores cerebrum blood supply and protects its nerve cells from death.

Under anaesthetic, the rats’ medium cerebral artery was pinched in order to impair the blood supply in the left hemisphere. Three days later, the animals were intravenously injected the mesenchymal stem cells (MSC) from the marrow. These cells are able to differentiate into the cells of other tissues, including nerve cells.

One group of the animals were false-operated – the operation was performed on them but the artery had not been pinched. The reference group animals’ artery was pinched but the stem cells were not introduced. The MSCs for transplantation were singled out from the marrow of thigh-bones of other animals of the same laboratory line, the MSCs were marked by a fluorescent dye and injected into the laboratory rats’ caudal vein. The animals’ cerebrum was investigated six weeks later.

Specialists of the “Trans-Technologies” Open Joint-Stock Company, with participation of Scientific Research Institute of Experimental Medicine, Russian Academy of Medical Sciences (St. Petersburg) were involved with the research.

There turned out to be unexpectedly few luminescent cells in the cerebrum specimen, and they were located not in the affected cortex zone but nearby ventricles of brain. This is strange as the specialists of “Tans-Technologies” have experimentally shown that stem cells introduced into the bloodstream come to the damaged tissue in several days. But nevertheless the stem cells introduction turned out effective for restoration of the affected brain. The area of affected zone with the experimental rats was less than that with the untreated animals.

Transplantation enables to preserve the parts of brain responsible for formation of emotions and motion regulation. With the untreated rats, these sections were noticeably damaged. Their stroke area was surrounded with an extensive zone of dying nerve cells. The stem cells increased almost by twice the number of blood vessels in the injured left hemisphere, which contributed to cerebral blood supply restoration. It is interesting that more vessels appeared in the symmetrical unaffected hemisphere. This phenomenon has not been described in scientific publications, therefore the researchers are planning to investigate it separately.

Thanks to the stem cells, the rats successfully passed the test in two or three weeks after transplantation. They became calmer, they better orientated themselves in space and memorized disposition of surrounding objects. Besides, the animals restored symmetry of reactions in the left and the right side of the body and in utilization of extremities.

In the researchers’ opinion, the mesenchymal stem cells (MSCs) is practically an ideal material for cellular therapy as they can be introduced directly into the blood. This allows to avoid serious operations under general anaesthetic, which are necessary for cell injection directly into the brain.

Although the researchers are now unable to fully explain the MSCs mechanism of action, but their beneficial action on the brain after a stroke is evident. Possibly, in case of earlier MSC transplantation, more cells will be able to get into the brain, and the beneficial action will be even more apparent.

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Mechanisms of Nerve Cell Death

Dr. Yin has been engaged in studying the complex mechanisms of cell death after stroke, spinal cord injury and other relevant neurodegenerative disorders such as Alzheimer’s disease using cell biology, molecular biology, biochemistry, and pharmacology approaches. Currently, effective treatments of these diseases are not available and the potential benefit of either medical or surgical treatment remains debatable. His major interest is to investigate the molecular regulation of apoptotic cell death in amyloid-beta induced endothelial cell death, ischemic brain damage and traumatic spinal cord injury, focusing on delineating the role of several key regulators of apoptosis (BH3-only family members) and multiple regulatory signaling pathways that regulate these apoptosis-related genes. Both in vitro and in vivo models of Alzheimer’s disease and CNS injury are employed in these studies.

By understanding these molecular mechanisms, the main goal of his research is to identify critical therapeutic targets which may lead to the development of novel neuroprotective strategies to attenuate CNS injury following cerebral ischemia, trauma to the spinal cord, and to prevent complications of cerebral amyloid angiopathy and related hemorrhagic stroke in the elderly.

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