Scaffold-Free Cartilage Construct from Infrapatellar Fat Pad Stem Cells for Cartilage Restoration.

Abstract

Once damaged, the articular cartilage has a very limited intrinsic capacity for self-renewal due to its avascular nature. If left untreated, damaged cartilage can lead to progressive degeneration of bone and eventually causes pain. Infrapatellar fat pad adipose-derived mesenchymal stromal cells (IPFP-ASCs) has a potential role for cartilage restoration. However, the therapeutic role for IPFP-ASCs remains to be evaluated in an appropriate osteochondral defect model. Thus, this study aimed to investigate the potential of using a three-dimensional (3D) cartilage construct of IPFP-ASCs as a promising source of cells to restore articular cartilage and to attenuate pain associated with the cartilage defect in an osteochondral defect model. The chondrogenic differentiation potential of the 3D cartilage construct derived from IPFP-ASCs was determined before implantation and postimplantation by gene expression and immunohistochemistry analysis. Pain-related behavior was also assessed by using a weight-bearing test. A significant pain-associated with the osteochondral defect was observed in this model in all groups postinduction; however, this pain can spontaneously resolve within 3 weeks postimplantation regardless of implantation of IPFP-ASCs constructs. The expression of SOX9 and COL2A1 genes in addition to protein expression were strongly expressed in 3D construct IPFP-ASCs. The existence of mature chondrocytes, along with significant (p < 0.05) positive immunostaining for type II collagen and aggrecan, were identified in the implanted site for up to 12 weeks compared with the untreated group, indicating hyaline cartilage regeneration. Taken together, this study demonstrated the successful outcome of osteochondral regeneration with scaffold-free IPFP-ASCs constructs in an osteochondral defect rat model. It provides novel and interesting insights into the current hypothesis that 3D construct IPFP-ASCs may offer potential benefits as an alternative approach to repair the cartilage defect. Impact statement This study provides evidence of using the human 3D scaffold-free infrapatellar fat pad adipose-derived mesenchymal stromal cells (IPFP-ASCs) construct to restore the full-thickness osteochondral defect in a rat model. This study showed that chondrogenic features of the construct could be retained for up to 12 weeks postimplantation. The results of this proof-of-concept study support that human 3D scaffold-free IPFP-ASCs construct has potential benefits in promoting the hyaline-like native cartilage restoration, which may be beneficial as a tissue-specific stem cell for cell-based cartilage therapy. There are several clinical advantages of IPFP-ASC including ease and minimal invasive harvesting, chondrogenic inducible property, and tissue-specific progenitors in the knee.