Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2019; 11(12): 1115-1129
Published online Dec 26, 2019. doi: 10.4252/wjsc.v11.i12.1115
Anti-osteoarthritis effect of a combination treatment with human adipose tissue-derived mesenchymal stem cells and thrombospondin 2 in rabbits
Kyungha Shin, Yeseul Cha, Young-Hwan Ban, Da Woom Seo, Ehn-Kyoung Choi, Dongsun Park, Sung Keun Kang, Jeong Chan Ra, Yun-Bae Kim
Kyungha Shin, Yeseul Cha, Young-Hwan Ban, Da Woom Seo, Ehn-Kyoung Choi, Yun-Bae Kim, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Chungbuk, South Korea
Dongsun Park, Department of Biology Education, Korea National University of Education, Cheongju 28173, Chungbuk, South Korea
Sung Keun Kang, Jeong Chan Ra, Biostar Stem Cell Research Institute, R-BIO Co., Ltd., Seoul 07238, South Korea
Author contributions: Shin K, Cha Y, and Ban YH performed animal experiments and assembled histological samples; Seo DW performed the cell differentiation study; Choi EK and Park D collected and analyzed the data; Kang SK prepared and characterized the stem cells; Ra CJ and Kim YB designed and interpreted the study, and wrote the manuscript.
Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to Y.B.K., No. 2017R1A2A2A05069417
Institutional review board statement: All human tissues were obtained with approval of the Institutional Review Board of K-Stem Cell (Seoul, Korea).
Institutional animal care and use committee statement: All protocols and procedures of animal experiments complied with the Institutional Animal Care and Use Committee of Laboratory Animal Research Center at Chungbuk National University (Chungbuk, Korea).
Conflict-of-interest statement: The author has no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yun-Bae Kim, DVM, PhD, Professor, College of Veterinary Medicine, Chungbuk National University, 1 Chungdaero (Gaesin-dong), Cheongju 28644, Chungbuk, South Korea.
Telephone: +82-43-2613358
Received: February 27, 2019
Peer-review started: February 27, 2019
First decision: August 1, 2019
Revised: October 14, 2019
Accepted: November 4, 2019
Article in press: November 4, 2019
Published online: December 26, 2019
Research background

Mesenchymal stem cells (MSCs) reportedly differentiate into chondrocytes and have a potential for articular cartilage regeneration. Therefore, they may be a novel strategy for osteoarthritis (OA) treatment.

Research motivation

Since MSCs can be differentiated into osteocytes, adipocytes, and other cells, in addition to chondrocytes, the efficiency for OA treatment is limited. We tried to increase the ratio of chondrocytic differentiation of human adipose-derived MSCs (hADMSCs) with thrombospondin 2 (TSP2), thereby enhancing OA therapeutic efficacy.

Research objectives

The present study investigated whether TSP2 induces the chondrogenic differentiation of hADMSCs and potentiates the therapeutic effects of hADMSCs in OA rabbits.

Research methods

In vitro, the chondrogenic potential of TSP2 in hADMSCs was investigated by analyzing the expression of chondrogenic markers as well as NOTCH signaling genes in normal and TSP2 siRNA-treated stem cells. In vivo, hADMSCs were injected into the injured knees of OA rabbits alone or in combination with TSP2, and OA progression was monitored via gross, radiological, and histological examinations.

Research results

In hADMSC culture, TSP2 increased the expression of chondrogenic markers as well as NOTCH signaling genes, which were inhibited by TSP2 siRNA treatment. In vivo, combination treatment with hADMSCs and TSP2 not only attenuated cartilage degeneration, osteophyte formation, and extracellular matrix loss, but also decreased synovial inflammatory cytokines.

Research conclusions

TSP2 enhances chondrogenic differentiation of hADMSCs via JAGGED1/NOTCH3 signaling, and combination therapy with hADMSCs and TSP2 exerts synergistic effects in the cartilage regeneration of OA joints.

Research perspectives

We demonstrated the positive roles of TSP2 in the chondrogenic differentiation of hADMSCs and in OA therapy. TSP2 could be an adjunct therapeutic for enhancing the cartilage-restoring efficacy of hADMSCs.