Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 24, Issue 10, Pages 1981-1989Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2018.06.021
Keywords
Poor graft function; Allotransplant; Mesenchymal stem cells; Hematopoietic stem cells; Bone marrow microenvironment
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Funding
- National Natural Science Foundation of China [81570127, 81530046]
- Clinical Medicine Plus X Young Scholars Project of Peking University [PKU2018LCXQ002]
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81621001]
- National Key Research and Development Program [2017YFA0104500]
- Science and Technology Project of Guangdong Province of China [2016B030230003]
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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, 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 CD34r cells. In summary, the biologic 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. (C) 2018 American Society for Blood and Marrow Transplantation.
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