Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model

• Main Authors: Tomoharu Takagi, Tamon Kabata, Katsuhiro Hayashi, Xiang Fang, Yoshitomo Kajino, Daisuke Inoue, Takaaki Ohmori, Takuro Ueno, Junya Yoshitani, Ken Ueoka, Yuki Yamamuro, Hiroyuki Tsuchiya
• Format: Article
• Language: English
• Published: BMC 2020-10-01
• Series: BMC Musculoskeletal Disorders
• Subjects: Adipose-derived stem cells; Cell sheet; Osteoarthritis
• Online Access: http://link.springer.com/article/10.1186/s12891-020-03718-z

Abstract Background Subcutaneous adipose tissue represents an abundant source of multipotent adult stem cells named as Adipose-derived stem cells (ADSCs). With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model. Methods Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically. Results Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups. Conclusions Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes.