Leisheng Zhang1,2,3,4,5,6, Yimeng Wei7, Ying Chi7, Dengke Liu8, Sijun Yang9,10, Zhongchao Han11,7,10, Zongjin Li9. 1. The Postdoctoral Research Station, School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China. leisheng_zhang@163.com. 2. The Enterprise Postdoctoral Working Station, Tianjin Chase Sun Pharmaceutical Co., Ltd, Tianjin, 301700, China. leisheng_zhang@163.com. 3. Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, 250014, China. leisheng_zhang@163.com. 4. Precision Medicine Division, Health-Biotech (Tianjin) Stem Cell Research Institute Co., Ltd, Tianjin, 301700, China. leisheng_zhang@163.com. 5. State Key Laboratory of Experimental Hematology & National Clinical Research Center for Blood Disease, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. leisheng_zhang@163.com. 6. Jiangxi Research Center of Stem Cell Engineering, Jiangxi Health-Biotech Stem Cell Technology Co., Ltd, Shangrao, 334000, China. leisheng_zhang@163.com. 7. State Key Laboratory of Experimental Hematology & National Clinical Research Center for Blood Disease, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. 8. The Enterprise Postdoctoral Working Station, Tianjin Chase Sun Pharmaceutical Co., Ltd, Tianjin, 301700, China. 9. The Postdoctoral Research Station, School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China. 10. Jiangxi Research Center of Stem Cell Engineering, Jiangxi Health-Biotech Stem Cell Technology Co., Ltd, Shangrao, 334000, China. 11. Precision Medicine Division, Health-Biotech (Tianjin) Stem Cell Research Institute Co., Ltd, Tianjin, 301700, China.
Abstract
BACKGROUND: Current studies have enlightened the rosy prospects of human pluripotent stem cell (hPSC)-derived mesenchymal stem/stromal cells (MSCs) in regenerative medicine. However, systematic investigation of their signatures and applications with alternative biomaterials in osteoarthritis (OA) remains indistinct. METHODS: Herein, we initially took advantage of a small molecule library-mediated programming strategy for hPSC-MSC induction. Then, with the aid of multifaceted analyses such as flow cytometry (FCM), chromosome karyocyte and cell vitality, wound healing and microtubule formation assay and coculturing with T lymphocytes, we systematically evaluated the characterizations of signatures in vitro and the in vivo efficacy of hPSC-MSCs and HA hydrogel composite on rabbit osteoarthritis model. RESULTS: We found the combination of LLY-507 and AZD5153 was sufficient for high-efficiency CD73+CD90+CD105+CD31-CD34-CD45-HLA-DR- MSC induction from both hESCs and hiPSCs with stemness (POU5F1/SOX2/NANOG). The programmed hPSC-MSCs revealed conservative transcriptome variations and went through a heterogeneous intermediate-stage with mesenchymal-associated gene expression (NT5E, ENG, VIM and FN1) as well as displayed typical cytomorphology, immunophenotypes and normal karyotyping, multilineage differentiation potential, favorable cell vitality, proangiogenic and immunoregulatory properties in vitro. Meanwhile, the cell population exhibited preferable restorative and ameliorative function on OA rabbits with HA hydrogel in vivo. CONCLUSIONS: Collectively, we established a rapid and convenient procedure for hPSC-MSC generation without redundant manipulations. The fundamental and clinical studies upon osteoarthritis (OA) treatment would benefit tremendously from the combination of the inexhaustible hPSC-MSCs and advantageous biomaterials.
BACKGROUND: Current studies have enlightened the rosy prospects of human pluripotent stem cell (hPSC)-derived mesenchymal stem/stromal cells (MSCs) in regenerative medicine. However, systematic investigation of their signatures and applications with alternative biomaterials in osteoarthritis (OA) remains indistinct. METHODS: Herein, we initially took advantage of a small molecule library-mediated programming strategy for hPSC-MSC induction. Then, with the aid of multifaceted analyses such as flow cytometry (FCM), chromosome karyocyte and cell vitality, wound healing and microtubule formation assay and coculturing with T lymphocytes, we systematically evaluated the characterizations of signatures in vitro and the in vivo efficacy of hPSC-MSCs and HA hydrogel composite on rabbit osteoarthritis model. RESULTS: We found the combination of LLY-507 and AZD5153 was sufficient for high-efficiency CD73+CD90+CD105+CD31-CD34-CD45-HLA-DR- MSC induction from both hESCs and hiPSCs with stemness (POU5F1/SOX2/NANOG). The programmed hPSC-MSCs revealed conservative transcriptome variations and went through a heterogeneous intermediate-stage with mesenchymal-associated gene expression (NT5E, ENG, VIM and FN1) as well as displayed typical cytomorphology, immunophenotypes and normal karyotyping, multilineage differentiation potential, favorable cell vitality, proangiogenic and immunoregulatory properties in vitro. Meanwhile, the cell population exhibited preferable restorative and ameliorative function on OA rabbits with HA hydrogel in vivo. CONCLUSIONS: Collectively, we established a rapid and convenient procedure for hPSC-MSC generation without redundant manipulations. The fundamental and clinical studies upon osteoarthritis (OA) treatment would benefit tremendously from the combination of the inexhaustible hPSC-MSCs and advantageous biomaterials.
Entities:
Keywords:
Genetic variation; HA hydrogel; Immunoregulation; Osteoarthritis; Programming; hPSC-MSCs
Authors: Rebekah M Samsonraj; Michael Raghunath; Victor Nurcombe; James H Hui; Andre J van Wijnen; Simon M Cool Journal: Stem Cells Transl Med Date: 2017-10-26 Impact factor: 6.940
Authors: Bin Li; Shanshan Bai; Guangxin Yue; Jinyan Zhu; Min Zhang; Baiqing Yang; Jiafei Luo; Yang Sun; Leisheng Zhang; Xin Wang Journal: Front Cardiovasc Med Date: 2022-02-11