Emerging therapeutic approaches for multipotent mesenchymal stromal cells

Abstract

Multipotent mesenchymal stromal cells (MSCs) are rare cells resident in bone marrow and other organs capable of differentiating into mesodermal lineage tissues. MSCs possess immunomodulatory properties and have extensive capacity for ex-vivo expansion. Early clinical studies demonstrated safety and feasibility of infusing autologous MSCs and suggested a role in enhancing engraftment after hematopoietic cell transplant (HCT). Subsequent pilot studies using allogeneic MSCs showed safety but presented contradictory results regarding efficacy in treating graft-versus-host disease (GVHD). Larger, phase II allogeneic MSC infusion studies, including cells obtained from haploidentical and third-party donors, showed efficacy in GVHD treatment; however, recent randomized, placebo-controlled studies failed to corroborate these results. New investigations include MSC infusions in umbilical cord blood transplantation, MSC therapy for tissue regeneration/repair, harvest and use of MSCs from adipose tissue and cell-tracking/imaging studies using radionuclides, gene and fluorescent dye-labeled MSCs. MSCs remain the subject of intense investigation in HCT because of their differentiation potential and immunomodulatory properties. Whereas infusions of autologous, allogeneic and third-party donor MSCs are well tolerated, further research is needed to clarify the optimal methods for harvesting and expansion, optimal timing of administration and efficacy in the setting of HCT.