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Therapeutic Effects of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Combined with Cartilage Acellular Matrix Mediated Via Bone Morphogenic Protein 6 in a Rabbit Model of Articular Cruciate Ligament Transection

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Abstract

Osteoarthritis (OA) is a general joint disease. Cartilage damage is associated with a decrease in the density of chondrocytes. Mesenchymal stem cells (MSCs) differentiate into adipocytes, osteocytes and chondrocytes, and are an excellent source of cell therapy. Cartilage-derived extracellular matrix (ECM) promotes chondrogenesis of MSCs. However, the role of MSCs stimulated by ECM is not well known in OA. The purpose of this study is to determine the role of specific factors generated by the application of ECM and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) in managing OA symptoms. Cartilage acellular matrix (CAM), which is a cartilage-derived ECM, was used to promote the chondrogenesis of UCB-MSCs. Induced MSCs were analyzed using chondrogenic markers (aggrecan, collagen type 2, and SOX9) and bone morphogenic protein 6 (BMP6). BMP6 is known to be involved in early chondrogenesis of MSCs. As a result, treatment with CAM significantly increased the expression of chondrogenic markers and BMP6 in UCB-MSCs. Treatment with recombinant human BMP6 also dramatically increased the levels of chondrogenic markers in UCB-MSCs. In addition, UCB-MSCs and CAM were used to evaluate OA symptom improvement in a rabbit articular cruciate ligament transection (ACLT) model. Application of UCB-MSCs and CAM enhanced not only the structure and synthesis of proteoglycan and collagen type 2 but also anti-inflammatory effects in both rabbit joint and synovial fluid. Moreover, the detection of human cells and involvement of BMP6 were confirmed in rabbit cartilage tissues. This study indicates that therapeutic potential of UCB-MSCs with CAM is mediated via BMP6 in OA.

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  1. Institute for Stem Cell and Regenerative Medicine in Kangstem Biotech, Seoul, Republic of Korea

    Hyo-Jin Jeon, Kyung-Ae Yoon, Tae-Wook Kang, Yun-Beom Sim, Jongchan Ahn, Seunghee Lee, Kwang-Won Seo & Kyung-Sun Kang

  2. College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea

    Eun Suk An, Ehn-Kyung Choi & Yun-Bae Kim

  3. Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea

    Kyung-Sun Kang

  4. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea

    Kyung-Sun Kang

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Contributions

Conception and design of the study, KWS, YBK, KSK; acquisition of data, HJJ, KAY, ESA, TWK, YBS; analysis and interpretation of data, HJJ, SHL, EKC, JCA; drafting the manuscript, HJJ, JCA; All authors read and approved the final manuscript.

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Correspondence to Kwang-Won Seo, Yun-Bae Kim or Kyung-Sun Kang.

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This study received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

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This experiment was approved by the Institutional Animal Care and Use Committee (IACUC) of Chungbuk National University Laboratory Animal Research Center and performed in accordance with the Standard Operation Procedures (SOP) of the same facility.

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Jeon, HJ., Yoon, KA., An, E.S. et al. Therapeutic Effects of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Combined with Cartilage Acellular Matrix Mediated Via Bone Morphogenic Protein 6 in a Rabbit Model of Articular Cruciate Ligament Transection. Stem Cell Rev and Rep 16, 596–611 (2020). https://doi.org/10.1007/s12015-020-09958-9

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