JNKi- and DAC-programmed mesenchymal stem/stromal cells from hESCs facilitate hematopoiesis and alleviate hind limb ischemia

Stem Cell Research & Therapy

Nianhuan Zhao¹  Huixing Hou¹  Baoquan Song²  Zongjin Li³  Jiali Huo⁴  Zhibo Han⁴  Yimeng Wei⁴  Ying Liu⁴  Ying Chi⁴  Zhongchao Han⁴  Lei Zhang⁴  Wenxia Zhang⁴  Chengwen Li⁴  Leisheng Zhang⁴  Dengke Liu⁵ 

[1] Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University;Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University;School of Medicine, Nankai University;State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College;The Enterprise Postdoctoral Working Station, Tianjin Chase Sun Pharmaceutical Co., Ltd.;

关键词: Programming;    MSCs;    Hematopoiesis;    Hind limb ischemia;    hESCs;   

DOI  :  10.1186/s13287-019-1302-1

来源: DOAJ

【 摘 要 】

Abstract Background Mesenchymal stem/stromal cells (MSCs) derived from human embryonic stem cells (hESCs) are attractive for their hematopoietic-supporting or potential therapeutic effects. However, procedures for high-effective and scalable generation of MSCs from hESCs within 2 weeks are still unestablished, which also hinder the development and mechanism study of mesengenesis. Methods In this study, we aimed to establish a strategy for programming hESC differentiation into MSCs by practicing small-scale chemical compound screening. Then, we used flow cytometry, multi-lineage differentiation, and karyotype analyses to investigate the biological phenotypes of the derived hESC-MSCs. Also, to explore whether the derived cells had hematopoietic-supporting ability in vitro, we carried out the cobblestone formation and megakaryocytic differentiation experiments. To further evaluate the function of hESC-MSCs in vivo, we transplanted the cells into a mouse model with hind limb ischemia. Results By simultaneous treatments with a JAK/STAT antagonist and a DNA methylation inhibitor, the efficiency of generating hESCs into CD73+ hESC-MPCs could reach 60% within 7 days. The derived cells further matured into hESC-MSCs, with comparable characteristics to those of adult MSCs in terms of surface markers, normal karyotype, and the potential for adipogenic, osteogenic, and chondrogenic differentiation. Functionally, hESC-MSCs had hematopoietic-supporting effects in vitro and could notably relieve symptoms of hind limb ischemia. Conclusions In the study, we established a high-efficient procedure for large-scale generation of MSCs from hESCs, which would be of great help for genesis and mechanism studies of MSCs. Meanwhile, the derived cells provide an alternative for translational clinical research.

【 授权许可】

Unknown