Despite the controversy over the differentiative potential of adult bone marrow stem cells, researchers have explored the possibilities of hastening
Recent Studies of Mesenchymal Stem Cell Transplantation in Rodent Models of Neurological Disorders
Cerebral ischemia 65-67, 87
TBI/spinal contusion 68, 69
Spinal cord demyelination 75, 89
recovery of neurological deficits by the transplantation of bone marrow cells. In rodent models of stroke, Parkinson's disease, multiple sclerosis, trauma, and neurodegeneration, direct intracerebral grafting or systemic administration of bone marrow cells helped promote functional recovery (Table 1). Rats subjected to MCAO performed significantly better in motor and somatosensory behavior tests when treated with intravenous or intracarotid administration of MSCs 1 d or 7 d after ischemia (67,87). Similarly, direct transplantation of MSCs into the ischemic hemispheres of mice or rats 1-7 d after MCAO improved functional recovery from the rotarod, limb placement, or modified neurologic severity score tests (65,66).
In the MPTP model of Parkinson's disease, mice transplanted with MSCs by intrastriatal injection at 1 wk after MPTP administration performed significantly better on the rotarod test compared with controls (88). Delayed injection of MSCs into the rat spinal cord 1 wk after contusion led to long-term improvement of locomotor function (68), and MSCs injected intravenously into rats after traumatic brain injury reduced motor and neurological deficits by d 15 (69). Moreover, regeneration of the axotomized sciatic nerve was accelerated by the local transplantation of MSCs predifferentiated into a Schwann cell-like phenotype (76). MSCs were also found to remyelinate the rat spinal cord after focal demyelination induced by irradiation/ethidium bromide (75,89). Finally, survival of a knockout mouse model of Niemann-Pick disease was enhanced after intracerebral transplantation of MSCs genetically engineered to express acid sphingomyelinase (90). Thus, the use of bone marrow stem cells holds great promise for the treatment of debilitating CNS disorders.
However, it should be quite clear from the presented evidence that the differentiation of bone marrow stem cells into neurons and macroglia is a rare biological event that can only partially account for the dramatic therapeutic effects observed with bone marrow transplantation in models of neurological diseases. These effects are more likely mediated by the concomitant increase in trophic factors (91). Nevertheless, as the signals instructing stem cells to adopt a particular cell fate are elucidated, the bone marrow compartment may turn out to be a valuable source of all kinds of cells destined for the CNS. As secluded as the CNS may appear, we are now beginning to realize that there may be a way from marrow to brain.
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