Regenerative effects of human chondrocyte sheets in a xenogeneic transplantation model using immune‐deficient rats

Abstract

Although cell transplantation has attracted much attention in regenerative medicine, animal models continue to be used in translational research to evaluate safety and efficacy because cell sources and transplantation modalities are so diverse. In the present study, we investigated the regenerative effects of human chondrocyte sheets on articular cartilage in a xenogeneic transplantation model using immune‐deficient rats. Osteochondral defects were created in the knee joints of immune‐deficient rats that were treated as Group A, untreated (without transplantation); Group B, transplantation of a layered chondrocyte sheet containing 5.0 × 105 cells (layered chondrocyte sheet transplantation); Group C, transplantation of a synoviocyte sheet containing 5.0 × 105 cells (synoviocyte sheet transplantation); or Group D, transplantation of both a synoviocyte sheet plus a layered chondrocyte sheet, each containing 5.0 × 105 cells (synoviocyte sheet plus layered chondrocyte sheet transplantation). Histological evaluation demonstrated that Group B showed cartilage regeneration with hyaline cartilage and fibrocartilage. In Groups C and D, the defect was filled with fibrous tissue but no hyaline cartilage. Transplanted cells were detected at 4 and 12 weeks after transplantation, but the number of cells had decreased at 12 weeks. Our results indicate that layered chondrocyte sheet transplantation contributes to articular cartilage regeneration; this model proved useful for evaluating these regenerative effects.

Decellularized sturgeon cartilage extracellular matrix scaffold inhibits chondrocyte hypertrophy in vitro and in vivo

“…Nowadays, increasing number of patients who damage their articular cartilage because of aging, trauma or degenerative disease have greatly affected their life quantity and create a huge social burden (Makris, Gomoll, Malizos, Hu, & Athanasiou, 2015; Patel, Saleh, Burdick, & Mauck, 2019). Current strategies for repairing cartilage defects including microfracture, tissue debridement, and autologous or allogeneic cartilage transplantation have been developed, but severe limitations of them have been reported as well, such as inferior biomechanical property of the repaired region and limited appropriate cartilage donor tissue (Armiento, Alini, & Stoddart, 2019; Y. Liu, Zhou, & Cao, 2017; Takizawa et al., 2020). Cartilage tissue engineering (CTE) that combines biodegradable scaffolds, cells and biologically active molecules has been proved as a promising tool for repairing cartilage defects in both experimental models and clinical patients (Deng et al., 2019; Kwon et al., 2019).…”

Development of Injectable Polydactyly-Derived Chondrocyte Sheets

“…In conducting clinical studies on the transplantation of autologous chondrocyte sheets [ 20 ] and polydactyly-derived chondrocyte sheets for articular cartilage regeneration, we have reported the characteristics and therapeutic effects of both types of sheet in animal experiments using mini-pigs, rabbits, and rats [ 22 , 23 , 24 , 25 ]. Our previous flow cytometric analysis studies have shown that PD sheets express MSC markers and our histological analyses have shown that PD sheets are multiply stratified without stacking, as in autologous chondrocyte sheets [ 17 ].…”

Trends in Articular Cartilage Tissue Engineering: 3D Mesenchymal Stem Cell Sheets as Candidates for Engineered Hyaline-Like Cartilage

“…Cell sheet technology employing chondrocyte sources has shown preliminary success in both pre-clinical models and small cohort clinical studies [ 24 , 25 , 173 , 175 , 176 , 177 , 180 , 181 , 182 , 183 , 184 ]. Chondrocyte sheets adhere directly and spontaneously to cartilage tissue via retained endogenous ECM and adhesion proteins.…”

“…Notably, this strength of defect site adhesion for the undifferentiated chondrocyte sheets is sufficient to allow initial defect retention without suturing, and to withstand knee joint mechanical forces while maintaining long-term localization of transplanted cells [ 24 , 173 , 177 , 180 , 182 , 185 ]. This engraftment capability facilitates successful chondrocyte sheet induction of hyaline-like cartilage regeneration in articular cartilage focal chondral defects by 4 weeks post-transplantation [ 24 , 25 , 173 , 177 , 180 , 181 , 182 ] ( Figure 4 a–d).…”