| Literature DB >> 32094463 |
Chengxiang Xia1,2,3,4,5, Tongjie Wang1, Hui Cheng6,7, Yong Dong1,2, Qitong Weng1,2, Guohuan Sun6,7, Peiqing Zhou1,2, Kaitao Wang8, Xiaofei Liu1, Yang Geng1, Shihui Ma6,7, Sha Hao6,7, Ling Xu9,10,11, Yuxian Guan1, Juan Du1, Xin Du12,13, Yangqiu Li9,10,11, Xiaofan Zhu6,7, Yufang Shi14, Sheng Xu15, Demin Wang16,17, Tao Cheng18,19, Jinyong Wang20,21,22,23,24,25.
Abstract
Bone marrow (BM) mesenchymal stem cells (MSCs) are critical components of the BM microenvironment and play an essential role in supporting hematopoiesis. Dysfunction of MSCs is associated with the impaired BM microenvironment that promotes leukemia development. However, whether and how restoration of the impaired BM microenvironment can inhibit leukemia development remain unknown. Using an established leukemia model and the RNA-Seq analysis, we discovered functional degeneration of MSCs during leukemia progression. Importantly, intra-BM instead of systemic transfusion of donor healthy MSCs restored the BM microenvironment, demonstrated by functional recovery of host MSCs, improvement of thrombopoiesis, and rebalance of myelopoiesis. Consequently, intra-BM MSC treatment reduced tumor burden and prolonged survival of the leukemia-bearing mice. Mechanistically, donor MSC treatment restored the function of host MSCs and reprogrammed host macrophages into arginase 1 positive phenotype with tissue-repair features. Transfusion of MSC-reprogrammed macrophages largely recapitulated the therapeutic effects of MSCs. Taken together, our study reveals that donor MSCs reprogram host macrophages to restore the BM microenvironment and inhibit leukemia development.Entities:
Mesh：
Year: 2020 PMID： 32094463 PMCID： PMC7987218 DOI： 10.1038/s41375-020-0775-3
Source DB: PubMed Journal: Leukemia ISSN： 0887-6924 Impact factor: 11.528