Dysfunctional Bone Marrow Mesenchymal Stem Cells in Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation |
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Authors: | Yang Song Hong-Yan Zhao Zhong-Shi Lyu Xie-Na Cao Min-Min Shi Qi- Wen Fei-Fei Tang Yu Wang Lan-Ping Xu Xiao-Hui Zhang Xiao-Jun Huang Yuan Kong |
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Affiliation: | 1. Peking University People''s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, China;2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China |
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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, 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 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. |
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Keywords: | Poor graft function Allotransplant Mesenchymal stem cells Hematopoietic stem cells Bone marrow microenvironment |
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