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Theranostics 2019; 9(22):6587-6600. doi:10.7150/thno.35391 This issue Cite

Research Paper

Transplantation of human ESC-derived mesenchymal stem cell spheroids ameliorates spontaneous osteoarthritis in rhesus macaques

Bin Jiang^1,2*, Xufeng Fu^1,3*, Li Yan^2*, Shanshan Li^1*, Dongliang Zhao⁴, Xiaoyan Wang², Yanchao Duan¹, Yaping Yan¹, Enqin Li², Kunhua Wu⁵, Briauna Marie Inglis¹, Weizhi Ji^1✉, Ren-He Xu^2✉, Wei Si^1✉

1. Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
2. Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
3. Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, China
4. Department of Radiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
5. Department of Magnetic Resonance Image, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China
^* These authors contributed equally.

✉ Corresponding authors: Weizhi Ji (wjicn), Ren-He Xu (renhexuedu.mo) or Wei Si (siwcn)

Abstract

It has been demonstrated that mesenchymal stem cells (MSCs) differentiated from human embryonic stem cells (hESCs), name EMSCs, can treat a variety of autoimmune and inflammatory diseases, with similar efficacies to those achieved with MSCs derived from somatic tissues such as bone marrow (BMSCs). The chance increases even higher for EMSCs, than somatic tissue derived MSCs​, to become a cell drug as the former can be produced in large scale from an unlimited hESC line with easier quality control and less biosafety concern. We have further demonstrated that both human ESCs and EMSCs, after aggregation to form spheroids, can tolerate hypoxic and ambient conditions (AC) for over 4 and 10 days, respectively, without loss of their viability and alteration of their functions. Based on these advantages, we decided to test whether EMSC spheroids, made in large quantity and delivered through a long-term distance at AC, can treat osteoarthritis spontaneously developed in rhesus macaques (M. mulatta) monkeys as well as the allogenic MSCs.

Methods: Xenogeneic AC-transported EMSC spheroids or allogenic BMSCs were injected into the articular cavity of both knees of the monkeys at 3 animals per group. Another two macaques were injected the same way with saline as controls.

Results: Both EMSCs and BMSCs groups showed significant amelioration indicated by the reduction of swelling joint size and amplification of keen flare angle post-treatment, compared to the control group. Examinations via X-ray and MRI also indicated the decrease of inflammation and osteophyma, and recovery of the synovium and cartilage in both treated groups. No sign of allergy or graft versus host disease was observed in the animals.

Conclusion: Our results demonstrate that human EMSC spheroids can prevent the osteoarthtitis progression and ameliorate osteoarthritis in the rhesus macaques as well as allogenic BMSCs, and this study shall help advance the clinical application of EMSCs.

Keywords: Mesenchymal stem cells, Osteoarthritis, Spheroids, AC tranportation, Rhesus macaques.

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