Biol Blood Marrow Transplant. 2018 Jun 19. pii: S1083-8791(18)30335-5. doi: 10.1016/j.bbmt.2018.06.021. [Epub ahead of print]

Dysfunctional bone marrow mesenchymal stem cells in patients with poor graft function after allogeneic hematopoietic stem cell transplantation.

Song Y¹, Zhao HY², Lyu ZS¹, Cao XN², Shi MM¹, Wen Q², Tang FF², Wang Y², Xu LP², Zhang XH², Huang XJ¹, Kong Y³.

Abstract

Poor graft function (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by defective hematopoiesis. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis, but little is known about the role of MSCs in the pathogenesis of PGF. In the current prospective case-control study, we evaluated whether the number and function of bone marrow (BM) MSCs in PGF patients differed from those in good graft function (GGF) patients. We found that BM MSCs from PGF patients expanded more slowly and appeared flattened and larger, exhibiting more apoptosis and senescence than MSCs from GGF patients. Furthermore, increased intracellular reactive oxygen species (ROS), p-p53, and p21 (but not p38) levels were detected in MSCs from PGF patients. Moreover, the ability of MSCs to sustain hematopoiesis was significantly reduced in PGF patients, as evaluated by cell number, apoptosis and the colony-forming unit-plating efficiency of CD34⁺ cells. In summary, the biological characteristics of PGF-MSCs are different from those of GGF-MSCs, and the in vitro hematopoiesis-supporting ability of PGF-MSCs is significantly lower. Although requiring further validation, our study indicates that reduced and dysfunctional BM MSCs may contribute to deficient hematopoiesis in PGF patients. Therefore, improvement of BM MSCs may represent a promising therapeutic approach for PGF patients after allo-HSCT.