Mesenchymal Stem Cells in Tissue Repair

Adult marrow-derived mesenchymal stem cells (MSCs) are able to differentiate into bone, cartilage, muscle, marrow stroma, tendon-ligament, fat and other connective tissues. The questions can be asked, what do MSCs do naturally and where is the MSC niche? New insight and clinical experience suggest that MSCs are naturally found as perivascular cells, summarily referred to as pericytes, which are released at sites of injury, where they secrete large quantities of bioactive factors that are both immunomodulatory and trophic. The trophic activity inhibits ischaemia-caused apoptosis and scarring while stimulating angiogenesis and the mitosis of tissue intrinsic progenitor cells. The immunomodulation inhibits lymphocyte surveillance of the injured tissue, thus preventing autoimmunity, and allows allogeneic MSCs to be used in a variety of clinical situations. Thus, a new, enlightened era of experimentation and clinical trials has been initiated with xenogenic and allogeneic MSCs.

Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders.

Cell-based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow-derived MSCs (BM-hMSCs) promote functional recovery in both chronic and relapsing-remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM-hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM-hMSC-induced changes in neural fate determination, since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than nontreated neurospheres. Host immune responses were also influenced by BM-hMSCs. Inflammatory T-cells including interferon gamma producing Th1 cells and IL-17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL-4 producing Th2 cells and anti-inflammatory cytokines. Together, these data suggest that the BM-hMSCs represent a viable option for therapeutic approaches.