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J Bone Miner Metab. 2019 Nov 23. doi: 10.1007/s00774-019-01055-3. [Epub ahead of print]

Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis.

Geng Y1,2,3, Chen J1, Alahdal M1,2,4, Chang C1, Duan L1,2, Zhu W1, Mou L1, Xiong J1,2, Wang M1, Wang D5,6.

Author information

1
The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China.
2
Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen, 518035, Guangdong Province, China.
3
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518035, Guangdong Province, China.
4
Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
5
The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. dapingwang1963@qq.com.
6
Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen, 518035, Guangdong Province, China. dapingwang1963@qq.com.

Abstract

INTRODUCTION:

Currently, osteoarthritis (OA) receives global increasing attention because it associates severe joint pain and serious disability. Stem cells intra-articular injection therapy showed a potential therapeutic superiority to reduce OA development and to improve treating outputs. However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. Recently, miR-140-5p was confirmed as a critical positive regulator in chondrogenesis. We hypothesized that hUC-MSCs overexpressing miR-140-5p have better therapeutic effect on osteoarthritis.

MATERIALS AND METHODS:

To enhance stem cell chondrogenic differentiation, we have transfected human umbilical cord mesenchymal stem cells (hUC-MSCs) with miR-140-5p mimics and miR-140-5p lentivirus to overexpress miR-140-5p in a short term or a long term accordingly. Thereafter, MSCs proliferation, chondrogenic genes expression and extracellular matrix were assessed. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of SD rats as an OA model, and then intra-articular injection of hUC-MSCs or hUC-MSCs transfected with miR-140-5p lentivirus was carried to evaluate the cartilage healing effect with histological staining and OARSI scores. The localization of hUC-MSCs after intra-articular injection was further confirmed by immunohistochemical staining.

RESULTS:

Significant induction of chondrogenic differentiation in the miR-140-5p-hUC-MSCs (140-MSCs), while its proliferation was not influenced. Interestingly, intra-articular injection of 140-MSCs significantly enhanced articular cartilage self-repairing in comparison to normal hUC-MSCs. Moreover, we noticed that intra-articular injection of high 140-MSCs numbers reinforces cells assembling on the impaired cartilage surface and subsequently differentiated into chondrocytes.

CONCLUSIONS:

In conclusion, these results indicate therapeutic superiority of hUC-MSCs overexpressing miR-140-5p to treat OA using intra-articular injection.

KEYWORDS:

Cartilage; Human umbilical cord mesenchymal stem cells; Osteoarthritis; miR-140-5p

PMID:
31760502
DOI:
10.1007/s00774-019-01055-3

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