Date Published: December 10, 2011
Publisher: Hindawi Publishing Corporation
Author(s): Yi Lin, William J. Hogan.
Mesenchymal stem cells (MSCs) represent a heterogeneous population of stromal cells with pluripotent mesenchymal differentiation potential. They have been found to have immunosuppressive properties and the ability to modulate angiogenesis and endogenous tissue repair by in vitro and animal studies. Clinical trials have examined the utility of these cells in autoimmune and inflammatory conditions. In particular, in allogeneic hematopoietic stem cell transplant (HSCT), multiple studies have been conducted to explore the use of MSC to treat acute and chronic graft-versus-host disease (GVHD) and for cotransplantation with HSCT to promote HSC engraftment and prevent GVHD. We review here the results of these studies and discuss some challenges of this treatment modality in this disease setting.
Mesenchymal stem cell and multipotent mesenchymal stromal cells are both designated MSC nomenclature by the latest consensus statement from the International Society for Cellular Therapy (ISCT) . This is a group of heterogeneous plastic-adherent cells that can be isolated from bone marrow (BM), adipose tissue, placenta, cord blood, and other tissues. The name MSC simply implies the mesenchymal origin of these cells and is not necessarily the limit of their differentiation potential. Given the heterogeneity of the stromal cell compartment and the limited number of these cells that have true stem-cell-like properties, consistent characterizations of MSC were proposed to maximize intersample equivalency in data comparison . Three criteria are now commonly used among researchers:
In some animal models, MSC infusion improved the survival of skin and solid organ grafts [4, 16, 19, 21]. Some patients in previously described studies who were at risk of graft failure or rejection had good response with MSC infusion . This prompted a number of investigators to examine the use of MSC cotransplant with HSCT to promote engraftment and prevent GVHD.
In conclusion, clinical evidence suggests that MSC may have some activity in the treatment and prevention of GVHD; however the largest randomized trials have not confirmed this to date. A better understanding of the underlying biology is needed to rationally design further phase III trials attempting to confirm efficacy and clarify risk of disease relapse and infection. Optimization of MSC therapy in GVHD and other clinical conditions will require better understanding of these cells’ mechanism of action and how these functions are affected by other existing treatment modalities. This knowledge can then be translated to improve the design of MSC therapy. Advances in personalized medicine should be employed to identify the patient population likely to benefit from MSC therapy and the role of MSC in combination with existing treatment modalities.