Rapamycin Promotes the Expansion of Myeloid Cells by Increasing G-CSF Expression in Mesenchymal Stem Cells

Minghao Li; Yanjie Lan; Juan Gao; Shengnan Yuan; Shuaibing Hou; Tengxiao Guo; Fei Zhao; Yuxia Wang; Weiping Yuan; Xiaomin Wang

doi:10.3389/fcell.2022.779159

Rapamycin Promotes the Expansion of Myeloid Cells by Increasing G-CSF Expression in Mesenchymal Stem Cells

Front Cell Dev Biol. 2022 Mar 17:10:779159. doi: 10.3389/fcell.2022.779159. eCollection 2022.

Authors

Minghao Li^{1

2}, Yanjie Lan¹, Juan Gao³, Shengnan Yuan¹, Shuaibing Hou¹, Tengxiao Guo¹, Fei Zhao¹, Yuxia Wang¹, Weiping Yuan¹, Xiaomin Wang^{1

4}

Affiliations

¹ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
² Shanghai Blood Center, Shanghai, China.
³ Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology, Tianjin Medical University, Nankai University Affiliated Eye Hospital, Tianjin, China.
⁴ Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Abstract

Rapamycin, also known as sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), is a regulatory kinase responsible for multiple signal transduction pathways. Although rapamycin has been widely used in treating various hematologic diseases, the effects of rapamycin are still not fully understood. Here we found that both oral and intraperitoneal administration of rapamycin led to the expansion of myeloid lineage, while intraperitoneal administration of rapamycin impaired granulocyte differentiation in mice. Rapamycin induced bone marrow mesenchymal stem cells to produce more G-CSF in vitro and in vivo, and promoted the myeloid cells expansion. Our results thus demonstrated that intraperitoneal administration of rapamycin might promote the expansion of myeloid lineage while impair myeloid cell differentiation in vivo.

Keywords: G-CSF; hematopoiesis; mTOR; myeloid cells; rapamycin.