hUC-MSCs can improve clinical manifestations in the animal model of EAE. There is compelling evidence that hUC-MSCs, compared to BM-MSCs, have higher proliferation and differentiation abilities, and stronger immune tolerance because of lower human leukocyte antigen-1 (HLA-1) expression ( 48, 49). They have a faster self-renewal ability compared to other MSCs ( 46), and they differentiate into a variety of cell types such as bone, cartilage, adipose, muscle, cardiomyocyte, neuron, astrocyte, and oligodendrocyte ( 47). hUC-MSCs are promising candidate sources of MSCs that can be collected without pain. Several studies have shown the therapeutic potential of human umbilical cord–derived mesenchymal stem cells (hUC-MSC) in MS patients. Clinical trials suggest that BMSCs have the potential to reduce infiltration, decrease demyelinated areas, and improve axonal formation and functional recovery ( 30). In experimental animal models, BMSCs have been shown to reduce immune attack to myelin sheets by suppressing T-lymphocyte proliferation ( 27, 28), diminishing inflammation and demyelination, inducing oligodendrogenesis ( 12), and improving remyelination ( 29) and tissue regeneration ( 10). Recovery of the demyelinated areas and promotion of remyelination following transplantation of glial progenitors derived from BMSCs in animal MS models have been documented ( 25, 26). Although the mechanisms that control neuroglial differentiation of BMSCs are not clearly understood, they can be differentiated into neuroglial phenotypes using growth factors, retinoic acid, and cytokines ( 23, 24). Transplantation of neuroglial progenitors derived from BMSCs enhances the homing and functional maturation rate of the cells ( 21, 22). The transplantation of differentiated BMSCs results in better glial cell engraftment than undifferentiated BMSCs. Auto transplantation of BMSCs in patients leads to significant recovery, and limits disability ( 19, 20). These results suggest that BMSCs are promising cell sources for functional recovery in MS patients. Several studies have confirmed the capacity of BMSCs to improve remyelination following experimental autoimmune encephalomyelitis (EAE) ( 17, 18). These neurotrophic and neuroprotective factors increase viability and proliferation of neuroglial cells and promote repair and recovery ( 15, 16). Furthermore, BMSCs have the ability to secrete many autocrine and/or paracrine factors that prevent apoptosis, and mediate neurogenesis and angiogenesis ( 13, 14). Transplantation of this cell population into damaged neural tissues leads to functional improvement via formation of glia and neurons that is identifiable at molecular and cellular levels ( 10– 12). BMSCs exhibit migration and homing ability into damaged parts of CNS. They can be cultured and propagated easily in vitro, and autologous transplantation can be achieved without rejection ( 8, 9). Unlike other source of stem cells, ethical concerns or tumorigenic activity is not a concern with BMSCs. The anti-inflammatory, low immunogenicity, and multipotency characteristics of BMSCs render them as a desirable cell source in regenerative medicine ( 6, 7). They can also differentiate into neurons and glial cells ( 6, 7). Bone marrow mesenchymal stem cells (BMSCs) are multipotent stem cells that are derived from the bone marrow and have chondrogenic, osteogenic, and adipogenic differentiation capacities.
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