Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment

Chengxiang Xia, Tongjie Wang, Hui Cheng, Yong Dong, Qitong Weng, Guohuan Sun, Peiqing Zhou, Kaitao Wang, Xiaofei Liu, Yang Geng, Shihui Ma, Sha Hao, Ling Xu, Yuxian Guan, Juan Du, Xin Du, Yangqiu Li, Xiaofan Zhu, Yufang Shi, Sheng XuDemin Wang, Tao Cheng, Jinyong Wang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2375-2383
Number of pages9
JournalLeukemia
Volume34
Issue number9
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment'. Together they form a unique fingerprint.

Cite this