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; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
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.
Biol Blood Marrow Transplant. 2018 Oct;24(10):1981-1989. doi: 10.1016/j.bbmt.2018.06.021. Epub 2018 Jun 20.
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.
移植物功能不良（PGF）是异基因造血干细胞移植（allo-HSCT）的一种危及生命的并发症，其特征是造血功能缺陷。间充质干细胞（MSCs）已被证明可支持造血，但对于 MSCs 在 PGF 发病机制中的作用知之甚少。在目前的前瞻性病例对照研究中，我们评估了 PGF 患者骨髓（BM）MSCs 的数量和功能是否与良好移植物功能（GGF）患者的不同。我们发现，PGF 患者的 BM-MSCs 扩增速度较慢，形态变平且较大，凋亡和衰老程度高于 GGF 患者的 MSCs。此外，在 PGF 患者的 MSCs 中检测到细胞内活性氧、p-p53 和 p21（而非 p38）水平增加。此外，PGF 患者的 MSCs 维持造血的能力明显降低，表现在 CD34 细胞的细胞数量、凋亡和集落形成单位-平板效率。总之，PGF MSCs 的生物学特征与 GGF MSCs 不同，PGF MSCs 的体外造血支持能力明显降低。尽管需要进一步验证，但我们的研究表明，减少和功能失调的 BM-MSCs 可能导致 PGF 患者造血功能不足。因此，改善 BM-MSCs 可能代表 allo-HSCT 后 PGF 患者有希望的治疗方法。
