Treatment of osteoarthritis with collagen-based scaffold: A porcine animal model with xenograft mesenchymal stem cells
Wo-Jan Tseng1*, Shu-Wei Huang2*, Chih-Hsiang Fang2, Lih-Tao Hsu3, Chih-Yu Chen4, Hsin-Hsin Shen3, Jenny Zwei-Chieng Chang5, Jui-Sheng Sun6 and Feng-Huei Lin2
1National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, 2Institute of Biomedical Engineering, National Taiwan University, Taipei, 3Center for Combination Product, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Chu-Tung, Hsin-Chu County, 4Department of Orthopedics, Shuang Ho Hospital of Taipei Medical University, New Taipei City, 5School of Dentistry, College of Medicine, National Taiwan University and 6Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan
*The first 2 authors (WR Tzeng & SW Huang) contribute equally in this work
Offprint requests to: Jui-Sheng Sun, MD, PhD., Department of Orthopedic Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan, No. 1, Sec. 1, Ren-Ai Rd., Taipei 10051, Taiwan, R.O.C. and Department of Orthopedic Surgery, National Taiwan University Hospital. No. 7, Chung-Shan South Rd., Taipei 10002, Taiwan, R.O.C. e-mail: drjssun@gmail.com or Feng-Huei Lin, PhD., Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan No. 1, Sec. 1, Ren-Ai Rd., Taipei 10051, Taiwan, R.O.C. e-mail: double@ntu.edu.tw
Summary. Objective. With the goal to explore a new approach to treat the early degenerative lesions of hyaline cartilage, we implanted in a porcine OA model a collagen-based scaffold containing chondroprogenitor cells derived from human bone marrow mesenchymal stem cells (hBM-MSCs). Experimental design. Porcine knee joints were subjected to anterior cruciate ligament (ACL) transection to surgically induce OA. After 4 months, the time necessary for the development of cartilage surface damage, animals were treated either with trephination bone plug wrapped with the chondroprogenic hBM-MSCs-embedded collagen scaffold or microfractures alone. Histological and histomorphometric evaluations were performed at 5 months after surgery. Results. All animals subjected to ACL transection showed osteoarthritic changes including mild lateral femoral condyle or moderate medial femoral condyle ulcerations. After 14 days' chondrogenic induction, hBM-MSCs seeded onto the scaffold showed expression of chondroprogenitor markers such as SOX9 and COMP. At 5 months after the implantation, significant differences in the quality of the regenerated tissue were found between the hBM-MSCs-embedded scaffold group and the control group. Newly generated tissue was only observed at the site of implantation with the hBM-MSCs-embedded scaffolds. Furthermore, histological examination of the generated tissue revealed evidence of cartilage-like tissue with lacuna formation. In contrast, fibrous layers or fissures were formed on the surface of the control knee joint. Conclusions. This study shows that xenogenic hBM-MSC derived chondroprogenitor scaffolds can generate new cartilage tissue in porcine articular cartilage and have the potential as a useful treatment option for osteoarthritis. Histol Histopathol 33, 1271-1286 (2018)
Key words: Osteoarthritis (OA), Porcine animal model, xenograft, Bone marrow-mesenchymal stem cell (BM-MSC), Chondroprogenitor, Scaffold
DOI: 10.14670/HH-18-013