Innovita Research Foundation

I.R.F. / Aging news / Diseases / 05061301

BM Transplantation Leads to Neural Generation
Posted on: June 13, 2005

Adult bone marrow stem cells seem to differentiate into muscle, skin, liver, lung, and neuronal cells in rodents and have been shown to regenerate myocardium, hepatocytes, and skin and gastrointestinal epithelium in humans. The question is: do bone marrow cells graft neural tissue in humans. This is of great importance in treatment of neurodegenerative disorders, neural trauma or other CNS pathologies with the use of stem cell transplants. Neurogenesis used to be thought to be completed during embryonic life in rodents as well as humans. During the last decade, however, numerous studies have suggested that neurogenesis continues in adult animals and humans, at least to a certain extent in a few privileged areas of the brain. Most of these studies have focused on endogenous neural progenitor cells (neural stem cells) localized in the subventricular zone of the lateral ventricle and in the dentate gyrus in the hippocampus in rodents. In the monkeys these cells are present in the hippocampus and neocortex. Likewise, Eriksson et al. found that new neurons are generated continuously in the human dentate gyrus throughout life. It is also conceivable that stem cells from other sources might enter the brain and form neurons there. Uchida et al. isolated CNS stem cells from human fetal tissue and transplanted them into the brains of mice, where they subsequently proliferated and differentiated into neuronal cells. One source of such cells in the brain could be the bone marrow. Adult bone marrow stem cells seem able to differentiate into muscle, skin, liver, lung, and neural cells in rodents. Furthermore, transplanted bone marrow cells in humans have also been shown to form myocardial cells, hepatocytes, and epithelium of the skin and gastrointestinal tract. Because it has been demonstrated that transplanted bone marrow cells migrate into the brains of mice and give rise to neurons there, it was hypothesized that the same thing might occur in the human CNS after bone marrow transplantation. This hypothesis was tested by looking for Y chromosome-positive neuron-like cells in postmortem brain samples from females who had received bone marrow transplants from male donors. The underlying diseases of the patients were lymphocytic leukemia and genetic deficiency of the immune system, and they survived between 1 and 9 months after transplant. A combination of immunocytochemistry (utilizing neuron-specific antibodies) and fluorescent in situ hybridization histochemistry to search for Y chromosome positive cells was used. In all four patients studied cells containing Y chromosomes in several brain regions were found. Most of them were non-neuronal (endothelial cells and cells in the white matter), but neurons were certainly labeled, especially in the hippocampus and cerebral cortex. The youngest patient (2 years old), who also lived the longest time after transplantation, had the greatest number of donor-derived neurons (7 in 10,000). The distribution of the labeled cells was not homogeneous. There were clusters of Y-positive cells, suggesting that single progenitor cells underwent clonal expansion and differentiation. But nevertheless it could be truly stated that adult human bone marrow cells can enter the brain and generate neurons just as rodent cells do. Perhaps this phenomenon could be exploited to prevent the development or progression of neurodegenerative diseases or to repair tissue damaged by infarction or trauma.

Source: Eva Mezey, Sharon Key, Georgia Vogelsang, Ildiko Szalayova, G. David Lange, and Barbara Crain; Transplanted bone marrow generates new neurons in human brains; 1364-1369 PNAS; February 4, 2003; vol. 100; no. 3; http://www.pnas.org/cgi/doi/10.1073/pnas.0336479100
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