Dominant role of in situ native cartilage niche for determining the cartilage type regenerated by BMSCs

Abstract Tissue-engineered cartilage regeneration by bone marrow stromal cells (BMSCs) is considered an ideal method. However, how to regulate BMSCs to regenerate specific types of cartilage remains unclear, which significantly limits its clinical translation and leads to suboptimal clinical effects. Herein, we systematically explored the role of native ear and articular cartilage niches on the differentiation fate of BMSCs and the type of regenerated cartilage. First, we prepared two types of acellular cartilage sheets (ACSs) and two types of chondrocytes. Then green fluorescent protein-labeled BMSCs were seeded on two types of ACSs with or without corresponding types of chondrocytes using a sandwich model and directed or cross-implanted them into native cartilage niches. After one year of in vivo culture, cell tracking and the results of histological results showed that the native cartilage niches were capable of regulating BMSCs regeneration into specific types of cartilage that were consistent with the cartilage types of the implanted sites. Furthermore, even when the type of niche formed by ACSs or the biomimetic cartilage niche constructed by specific types of ACSs and specific types of chondrocytes did not match with the native cartilage niche, the native cartilage niche continued to determine the type of cartilage regenerated by implanted BMSCs and chondrocytes. All our results provide sufficient evidence for specific types of cartilage regeneration using chondrogenic potential cells, such as mesenchymal stem cells and chondrocytes.