Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis.
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.
['Geng|Yiyun|Y|', 'Chen|Jinfu|J|', 'Alahdal|Murad|M|', 'Chang|Chongfei|C|', 'Duan|Li|L|', 'Zhu|Weimin|W|', 'Mou|Lisha|L|', 'Xiong|Jianyi|J|', 'Wang|Manyi|M|', 'Wang|Daping|D|']
D000818:Animals D002358:Cartilage, Articular D002454:Cell Differentiation D019902:Chondrocytes D020219:Chondrogenesis D004195:Disease Models, Animal D006801:Humans D007270:Injections, Intra-Articular D016086:Lentivirus D008297:Male D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D035683:MicroRNAs D010003:Osteoarthritis D017207:Rats, Sprague-Dawley D012038:Regeneration D014470:Umbilical Cord
miR-140-5p Cartilage Osteoarthritis Human umbilical cord mesenchymal stem cells