Human ESC-MSCs And Fos Gene In Tenogenesis And Tendon Repair

Tendon injuries are commonly encountered in the clinic, disrupting the patient’s normal work/life routine and damaging the career life of athletes. At least30,000,000injuries are encountered annually. Currently, there is still no effective treatment for tendon injury. Current therapeutic options for tendon injury include conservative treatments (steroid injection, low-intensity pulsed ultrasound, shockwave and physiotherapy) and surgery (direct suture and autograft, allograft and permanent tendon prostheses). However, these methods have inherent shortcomings such as long recovery period, donor site morbidity, immunological rejection and tendon tissue necrosis. Therefore, new therapeutic strategies for tendon injury need to be developed.By utilizing a combination of seed cells, biomaterials and suitable microenvironmental factors, tendon tissue engineering aims to replace the injured tendon through graft implantation. Stem cells have been widely used due to their excellent proliferative capacity within in vitro culture and differentiation potential to tenocytes, such as ESCs, MSCs and TSPCs. However, current stem cell based tendon tissue engineering fails to fully regenerate the injured tendon. The repaired tendon is usually accompanied by the formation of fibro-scar, which is constituted of smaller-sized collagen fibrils. This cannot recapitulate the normal mechanics of tendon tissue, and the mechanical strength of tendon is difficult to recover. Thus, current strategies utilized in research are still far away from clinical applications due to lack of cellular differentiation to tendon/tenocytes. This thesis focuses on specific differentiating ESC-MSCs to teno-lineage for tendon repair.The current study includes three chapters:We firstly applied human ESCs derived MSCs for tendon repair and showed the great potential as an ideal seed cell of tendon tissue engineering. Then we screened the critical tendon differentiation related genes. We studied the development process of normal post-natal tendon by evaluating the structural alteration and inherent molecular difference. Micaroarray screen discovered the regulation effect of fos gene on tendon stage specific development and differentiation, which is further comfirmed by gene overexpression and gene knock-down experiments. In the third chapter, we overexpressed fos gene in human ESC-MSCs for early stage tendon differentiation. We found the cell differentiated into an early stage of tendon. This study provided important information for the future tendon tissue engineering application with ESCs and showed a new tendon differentiation strategy.