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Mesenchymal Stem Cells in Synovial Fluid Increase in Knees with Degenerative Meniscus Injury after Arthroscopic Procedures through the Endogenous Effects of CGRP and HGF

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Abstract

Background

Mesenchymal stem cells (MSCs) in synovial fluid increase after traumatic meniscus injuries. However, MSC kinetics in synovial fluid may differ for knees with degenerative meniscus injuries. Furthermore, the combination of surgical repair and synovial MSC transplantation has been found to improve clinical symptoms in patients with degenerative meniscus injury, and in this treatment, only the operation procedure without MSC transplantation might increase MSCs in synovial fluid; if so, soluble factors in synovial fluid will be involved. The purpose is this study was to examine whether MSCs exist in synovial fluid of knees with degenerative meniscus injury, to investigate whether MSCs in synovial fluid increase after harvest of synovium and meniscus repair, and to explore what soluble factors in synovial fluids affect the number of MSCs in synovial fluid.

Methods

Subjects were 7 patients with degenerative meniscus injury who underwent meniscal repair and synovial MSC transplantation. Synovial fluid (Pre) was aspirated from knees before harvest of synovium and meniscus repair. After 2 weeks, synovial fluid (Post) was aspirated again before transplantation of synovial MSCs. A half volume of the synovial fluid was plated and cultured for 2 weeks to count the colony formation. The other half was used for antibody array analysis, and the correlation coefficients between the signal intensity and colony number were measured in 503 factors. Factors with high correlation coefficients were verified by migration assay.

Results

While cell colonies derived from synovial fluid (Pre) were hardly observed, greater numbers of colonies from synovial fluid (Post) were demonstrated. Of the 503 factors, calcitonin gene-related peptide (CGRP) and hepatocyte growth factor (HGF) had high correlation coefficients between colony number and expression level. Both CGRP and HGF promoted migration of synovial fluid MSCs.

Conclusions

MSCs in synovial fluid were hardly seen in knees with degenerated meniscus injury. They significantly increased 2 weeks after harvest of synovium and meniscus repair. Both CGRP and HGF in synovial fluid can possibly induce MSCs from synovium into synovial fluid.

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Abbreviations

MSCs:

Mesenchymal stem cells

CGRP:

calcitonin gene-related peptide

HGF:

hepatocyte growth factor

OA:

osteoarthritis

α-MEM:

α-modified essential medium

HBSS:

Hank’s balanced salt solution

BMP-2:

bone morphogenetic protein 2

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Acknowledgments

We thank Ms. Mika Watanabe and Ms. Kimiko Takanashi for the management of our laboratory and Tina Hilling for English editing.

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Not applicable.

Funding

This research was supported by the Japan Agency for Medical Research and Development (AMED) under grant JP19bk0104065.

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Authors and Affiliations

  1. Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Naoto Watanabe, Kentaro Endo, Keiichiro Komori, Nobutake Ozeki, Mitsuru Mizuno, Hisako Katano, Yuji Kohno & Ichiro Sekiya

  2. Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan

    Kunikazu Tsuji

  3. Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Hideyuki Koga

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  1. Naoto Watanabe
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  2. Kentaro Endo
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  4. Nobutake Ozeki
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  5. Mitsuru Mizuno
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Contributions

All authors were involved in drafting the article or critically revising it for important intellectual content, and all authors approved the final manuscript. I.S. had full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analysis. N.W., K.E., and I.S. designed and performed the research, analyzed and interpreted the data, and drafted the manuscript. N.W. performed the experiments and collected the data. K.K. made substantial contributions to multidifferentiation analysis, flowcytometry, and protein array analysis. N.O., M.M., K.O., H.Ka., and Y.K. made substantial contributions to the analysis and interpretation of the data. K.T. made substantial contributions to the study design for migration assay. H.Ko. performed arthroscopy and collected synovial fluid from the patients.

Corresponding author

Correspondence to Ichiro Sekiya.

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This study was approved by the Medical Research Ethics Committee of Tokyo Medical and Dental University, and informed consent was obtained from all study subjects.

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Watanabe, N., Endo, K., Komori, K. et al. Mesenchymal Stem Cells in Synovial Fluid Increase in Knees with Degenerative Meniscus Injury after Arthroscopic Procedures through the Endogenous Effects of CGRP and HGF. Stem Cell Rev and Rep 16, 1305–1315 (2020). https://doi.org/10.1007/s12015-020-10047-0

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