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Open AccessArticle

Clinical-Grade Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Ameliorate the Progression of Osteoarthritis in a Rat Model

by 1,2,†, 1,2,†, 3,4,5,6,†, 1,2, 7, 8, 3,4,5, 3,4,5, 3,4,5,6,9, 3,4,5,6,9,* and 1,2,*
1
Arthritis Clinic & Research Center, Peking University People’s Hospital, Peking University, Beijing 100044, China
2
Arthritis Institute, Peking University, Beijing 100044, China
3
National Stem Cell Resource Center, Institute of Zoology, Chinese Academy of Sciences, Beijing 100190, China
4
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
5
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
6
Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
7
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China
8
School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW 2007, Australia
9
Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China
*
Authors to whom correspondence should be addressed.
These authors are equally contributed to this work.
Academic Editors: Weifeng Lin and Linyi Zhu
Molecules 2021, 26(3), 604; https://doi.org/10.3390/molecules26030604
Received: 25 December 2020 / Revised: 13 January 2021 / Accepted: 15 January 2021 / Published: 24 January 2021
(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)
Mesenchymalstem cell (MSC)-based therapy is being increasingly explored in preclinical and clinical studies as a regenerative method for treating osteoarthritis (OA). However, the use of primary MSCs is hampered by a number of limitations, including donor heterogeneity and inconsistent cell quality. Here, we tested the therapeutic potential of embryonic stem cell-derived MSCs (ES-MSCs) in anOA rat model. ES-MSCs were generated and identified by morphology, trilineage differentiation and flow cytometry. Sprague Dawley rats were treated with either a single dose (106 cells/rat) of ES-MSCs or with three doses spaced one week apart for each dose, starting at four weeks after anterior cruciate ligament transectionto induce OA. Cartilage quality was evaluated at 6 and 10 weeks after treatment with behavioral analysis, macroscopic examination, and histology. At sixweeks after treatment, the groups treated with both single and repeated doses of ES-MSCs had significantly better modified Mankin scores and International Cartilage Repair Society (ICRS) macroscopic scores in the femoral condyle compared to the control group. At 10 weeks after treatment, the repeated doses group had a significantly better ICRS macroscopic scores in the femoral condyle compared to the single dose and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, along with lower Mankin scores in the repeated doses group. In conclusion, treatment with multiple injections of ES-MSCs can ameliorate OA in a rat model. TheES-MSCs have potential to be considered as a regenerative therapy for OA, and can provide an infinite cellular source. View Full-Text
Keywords: embryonic stem cells; mesenchymal stem cells; osteoarthritis; cell therapy; tissue repair embryonic stem cells; mesenchymal stem cells; osteoarthritis; cell therapy; tissue repair
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MDPI and ACS Style

Xing, D.; Wang, K.; Wu, J.; Zhao, Y.; Liu, W.; Li, J.J.; Gao, T.; Yan, D.; Wang, L.; Hao, J.; Lin, J. Clinical-Grade Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Ameliorate the Progression of Osteoarthritis in a Rat Model. Molecules 2021, 26, 604. https://doi.org/10.3390/molecules26030604

AMA Style

Xing D, Wang K, Wu J, Zhao Y, Liu W, Li JJ, Gao T, Yan D, Wang L, Hao J, Lin J. Clinical-Grade Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Ameliorate the Progression of Osteoarthritis in a Rat Model. Molecules. 2021; 26(3):604. https://doi.org/10.3390/molecules26030604

Chicago/Turabian Style

Xing, Dan; Wang, Kai; Wu, Jun; Zhao, Yu; Liu, Wei; Li, Jiao J.; Gao, Tingting; Yan, Deng; Wang, Liu; Hao, Jie; Lin, Jianhao. 2021. "Clinical-Grade Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Ameliorate the Progression of Osteoarthritis in a Rat Model" Molecules 26, no. 3: 604. https://doi.org/10.3390/molecules26030604

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