Mesenchymal stromal cells for cell therapy: besides supporting hematopoiesis

Abstract

Mesenchymal stromal cells (MSC) have attracted the attention of scientists and clinicians due to their self-renewal, capacity for multipotent differentiation, and immunomodulatory properties. Some essential problems remain to be solved before the clinical application of MSC. Platelet lysate (PL) has recently been used as a substitute for FBS in MSC amplification in vitro to achieve clinically applicable numbers of MSC. In addition to promising trials in regenerative medicine, such as in the treatment of major bone defects and myocardial infarction, MSC have shown therapeutic effect other than direct hematopoiesis support in hematopoietic reconstruction. It has been confirmed that MSC promote hematopoietic cell engraftment and immune recovery after allogeneic hematopoietic stem cell transplantation, probably through the provision of cytokines, matrix proteins, and cell-to-cell contacts. Their suppressive effects on immune cells, including T cells, B cells, NK cells and DC cells, suggest MSCs as a novel therapy for GVHD and other autoimmune disorders. These cells thus present as promising candidates for cellular therapy in the fields of regenerative medicine, allogeneic hematopoietic stem cell transplantation, and autoimmune disorders.

The uncertain role of unmodified mesenchymal stem cells in tumor progression: what master switch?

“…Adipose-derived stem cells have been shown to lack MHC II expression and its immunosuppressive effects mediated by prostaglandin E2. The suppressive effects of MSCs on immune cells, including T cells, B cells, natural killer (NK) cells and dendritic cells suggest MSCs may be used as a novel therapeutic tool for GVHD and other autoimmune disorders [64]. However, MSCs apparently play multiple roles in immunoregulation in a circumstantial manner.…”

Umbilical cord blood transplantation supplemented with the infusion of mesenchymal stem cell for an adolescent patient with severe aplastic anemia: a case report and review of literature

“…The underlying mechanism of the immunomodulation of MSCs is not very clear, but growing evidence reveals that MSCs exhibit immunosuppressive activity on T cells,42–46 B cells,47,48 and natural killer (NK) cells 49–51. The underlying mechanism of hematopoiesis support of MSCs is supposed to be the effect of supporting the reconstruction of hematopoietic microenvironment in addition to direct hematopoiesis 52–54…”

Cancer gene therapy using mesenchymal stem cells

“…For example, TNF-a readily induces IL-6 and MCP-1 secretion by CAFs and normal FBs and has an indirect influence on the generation of a prometastatic microenvironment. Furthermore, TNF-a is released in cardiac infarction [46] and graft-versus-host disease [47,48]; MSCs accumulate at the site of cardiac infarction [49,50]. These results indicate that proinflammatory cytokines also promote homing of MSCs in the heart and that these cytokines have a positive effect on cardiac regeneration.…”