Mesenchymal Stem Cells in Allogeneic Transplantation

Graft failure and graft-vs-host disease (GVHD) remain significant obstacles to successful outcome in patients undergoing allogeneic hematopoietic stem cell transplantation. This chapter will introduce a novel cellular therapy, which may address these problems, particularly in high risk patients such as those receiving marginal numbers of hematopoietic progenitor cells (i.e., umbilical cord blood [UCB]) and those receiving unrelated donor or related but human leukocyte antigen (HLA)-mismatched donor progenitor cells. Several groups have described nonhematopoietic plastic-adherent progenitor cells derived from human bone marrow aspirates, which are capable of differentiating into mature mesenchymal cells (1–5). It is thought that these progenitors, called mesenchymal stem cells, give rise to adventitial and other mesenchymal cells in the marrow and constitute the microenvironment for hematopoiesis. Such cells fabricate the connective tissue scaffolding and produce cytokines, chemokines, and extracellular matrix proteins that regulate hematopoietic homing and proliferation (6,7). There is growing interest in cotransplantation of allogeneic mesenchymal and hematopoietic progenitors to facilitate hematopoietic engraftment and limit GVHD.