The Research Of Cartilage Defects Repair By Use Of Mesenchymal Stem Cells

Hyaline cartilage is easily injured, but due to its avascular and hypocellular nature, cartilage defects exhibit poor spontaneous healing instinct. If left untreated, the whole joint will soon progress to degeneration. It is reported that the incidence of cartilage defects in young man is about 20%. Cartilage defects bring a serious social problem. Currently, the most common treatment options for cartilage defects include articular debridement, microfracture and autologous osteochondral transplantation (OCT). However, none of these methods can generate hyaline like cartilage. Tisssue engineering is a promising way to restore the cartilage defects. Seeding cells, growth factors and scaffolds are three main factors of the tissue engineering. Nowdays, all these three factors have defaults, which significantly limit the repair quality of the tissue engineering. So, we conduct this project to improve these three factors, hoping can better repair the cartilage defects.This project focused on seeding cells, growth factors and scaffolds of tissue engineering. And, three studies have been conducted.Part 1:Synovium derived mesenchymal stem cell (SMSC) sheet was fabricated. The SMSC sheet combined with autologous OCT was used to repair full-thickness cartilage defects in Newzealand White Rabbits. Extracellular matrix (ECM) and cell-cell connection were all preserved well in cell sheet. Then, cell sheet may improve the quality of OCT. The osteochondral cylinders were wrapped with three layers of SMSC sheets and transplanted into cartilage defects. Eight weeks after the surgery, experimental group showed much better results with lighter degeneration and better healing at the cartilage margins. Part 2:mesenchymal stem cells (MSCs) have limited proliferation and differentiation ability. MSCs like cells derived from induced pluripotent stem cells (iPSCs) have the characteristics of both MSCs and iPSCs. In this study, MSCs derived from human iPSCs (hiPSC-MSCs) was prepared. Then, hiPSC-MSCs were plated onto (poly(lactic-cO-glycolic acid), PLGA) scaffold before tranplantion into full-thickness cartilage defects. Six weeks after surgery, experimental group showed cartilage like tissue in the cartilage defects. While, only fiber tissue was observed in control and scaffold transplantation group. Part 3:the scaffold that can mimic the environment of chondrocytes is good for cell proliferation and differentiation. Decellularized scaffold can fulfill this object. This study prepared decellularized osteochondral matrix and transplanted it into full-thickness cartilage defects in Newzealand White Rabbts. Twelve weeks after the operation, no cartilage like tissue was observed in all the groups. Maybe, the poor pore size and porosity lead to the poor results.The results of this study showed that three-layered SMSC sheets can significantly improve the repair quality of autologous OCT; hiPSC-MSCs can repair full-thickness cartilage defects in vivo; decellularized osteochondral matrix can not repair cartilage defects in vivo. To our knowledge, this study was the first to combine cell sheet technology with OCT in cartilage defects repair and proved iPSC-MSCs as a candidate seeding cells in cartilage tissue engineering. This study provide with foundation for future cartilage defets restoration.