Bone marrow stromal cells (BMSCs) are currently considered strong candidates for cell-based therapy in stroke (25). BMSCs are a mixed-cell population, including stem and progenitor cells, that can differentiate into mesenchymal cells, as well as cells with visceral mesoderm, neuroecto-derm, and endoderm characteristics (26). Although infrequent, these cells may differentiate into neural cells and endothelium in the brain. From experimental stroke in rodent, BMSCs derived from donor rats (6,27-30), mice (31,32), or humans (33,34) were transplanted into brain intracerebrally (28,31), intraarterially (29), intracisternally (32), or intravenously (27,30,33,34). BMSCs selectively target injured tissue and promote functional recovery. Signals that target inflammatory cells to injured tissue likely direct BMSCs to injury sites (35). Using a microchemotaxis chamber, we measured the effect of select chemotactic factors and cytokines expressed in injured brain, monocyte chemoattractant protein-1, macrophage inflammatoryprotein-1a, and interleukin-8, on migration of BMSCs. Ischemic brain tissue extracts significantly increased BMSC migration across the membrane, compared to nonischemic tissue (35). Recovery from neurologic deficits has not correlated with structural repair or reduction of the lesion in stroke models. Although some BMSCs express proteins phenotypic of neural cells, it is highly unlikely that therapeutic benefit is derived by replacement of infarct tissue with transdifferentiated BMSCs. Secretory functions of BMSC, such as the elaboration of growth and trophic factors, as well as the induction of trophic factors within parenchymal cells, have been hypothesized to play a role in the enhanced recovery of neurologic function. BMSCs activate endogenous restorative responses in injured brain, which include neurogenesis and synaptogenesis (27,33,36-38), angiogenesis, and vasculogenesis (32). Recent studies demonstrate that BMSCs stimulate glia and thereby promote appropriate neurite outgrowth and extension of axons to the injured hemisphere (6 ). Thus, constitutive reparative response is facilitated by a series of interactions between BMSCs and host cells, reducing scar tissue, fostering the reformation of brain tissue, and facilitating synaptic and vascular reconstitution. The advantages of using BMSCs are that they can be given as an autologous graft, avoiding risks of rejection and graft-versus-host reactions, and that they can be given intravenously, minimizing complications.
Increasing evidence supports the retention of toti/multi potent cells in the peripheral blood stromal cells and umbilical stem cells. Granulocyte colony stimulating factor-mobilized peripheral blood stromal cells in the circulating blood might be an alternative to bone marrow as a source of autologous stem cells. Peripheral blood stromal cells (39) and other stem cells, such as the umbilical stem cells, have been employed in rodent models of stroke (40). In these studies, groups of transplanted rodents showed a significant improvement in neurologic function, compared with nontransplanted stroked animals. These findings raise the possibility that marrow stromal cells (MSCs) from peripheral blood and umbilici could provide an effective transplantation therapy to treat stroke.
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