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JNKi- and DAC-programmed mesenchymal stem/stromal cells from hESCs facilitate hematopoiesis and alleviate hind limb ischemia
- Source :
- Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-14 (2019), Stem Cell Research & Therapy
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
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. Electronic supplementary material The online version of this article (10.1186/s13287-019-1302-1) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Stromal cell
Human Embryonic Stem Cells
Karyotype
Hind limb ischemia
Medicine (miscellaneous)
MSCs
Biology
Mesenchymal Stem Cell Transplantation
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Flow cytometry
Cell Line
lcsh:Biochemistry
03 medical and health sciences
Mice
0302 clinical medicine
Ischemia
medicine
Animals
Humans
lcsh:QD415-436
Mice, Inbred BALB C
lcsh:R5-920
medicine.diagnostic_test
Research
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
Cell Biology
Chondrogenesis
Flow Cytometry
equipment and supplies
Embryonic stem cell
Cell biology
Hindlimb
Hematopoiesis
Haematopoiesis
030104 developmental biology
Adipogenesis
030220 oncology & carcinogenesis
hESCs
embryonic structures
Leukocytes, Mononuclear
Programming
Molecular Medicine
Female
Stem cell
lcsh:Medicine (General)
Megakaryocytes
Subjects
Details
- Language :
- English
- ISSN :
- 17576512
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....1d422f3ad7ea81cd0072d9738f741fdd