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

  • Yiyun Geng
  • Jinfu Chen
  • Murad Alahdal
  • Chongfei Chang
  • Li Duan
  • Weimin Zhu
  • Lisha Mou
  • Jianyi Xiong
  • Manyi Wang
  • Daping WangEmail author
Original Article
  • 73 Downloads

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

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

Notes

Acknowledgements

The authors would like to thank Ling Wei and Hancheng Zhang for technical help on qPCR and immunohistochemical staining.

Author contributions

YG and DW designed the experiments; YG and JC conducted of the animal experiments; YG and CC conducted part of the cell experiments; WZ, JX and MW supervised the animal experiments; YG, LD and MA analyzed the results and wrote the manuscript. All authors read and approved the final manuscript.

Funding

This work was funded by National Natural Science Foundation of China (Nos. 81572198; 81772394); Key Program of Natural Science Foundation of Guangdong Province (No. 2018B0303110003); Shenzhen Peacock Project (KQTD20170331100838136); Shenzhen Science and Technology Projects (Nos. JCYJ20170817172023838; JCYJ20170306092215436; JCYJ20170412150609690; JCYJ20170413161649437; JCYJ20170413161800287; SGLH20161209105517753; JCYJ20160301111338144); Fund for High Level Medical Discipline Construction of Shenzhen University (No. 2016031638). Natural Science Foundation of Guangdong Province (2019A1515011108); Shenzhen Science and Technology Project (GJHZ20180416164801042, JCYJ20160226192924528), Shenzhen Double Chain Project for Innovation and Development Industry supported by Bureau of Industry and Information Technology of Shenzhen (201806081524201510).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

774_2019_1055_MOESM1_ESM.docx (141 kb)
Supplementary material 1 (DOCX 141 kb)

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Copyright information

© The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Yiyun Geng
    • 1
    • 2
    • 3
  • Jinfu Chen
    • 1
  • Murad Alahdal
    • 1
    • 2
    • 4
  • Chongfei Chang
    • 1
  • Li Duan
    • 1
    • 2
  • Weimin Zhu
    • 1
  • Lisha Mou
    • 1
  • Jianyi Xiong
    • 1
    • 2
  • Manyi Wang
    • 1
  • Daping Wang
    • 1
    • 2
    Email author
  1. 1.The First Affiliated Hospital to Shenzhen University, Health Science CenterShenzhen Second People’s HospitalShenzhenChina
  2. 2.Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic TechnologyShenzhenChina
  3. 3.Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesShenzhenChina
  4. 4.Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative MedicineZhejiang University School of MedicineHangzhouChina

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