bFGF-genetically modified bone marrow-derived mesenchymal stem cells promote tendon-to-bone interface healing by promoting chondrogenesis and regulating macrophage polarization.

BACKGROUND

Rapid regeneration and functional recovery of the enthesis following tendon-to-bone interface (TBI) injury remains a significant challenge. This study aims to investigate the feasibility of leveraging bFGF genetically modified bone marrow-derived mesenchymal stem cells (BMSCs) to enhance tendon-to-bone interface regeneration.

METHODS

The proliferation and chondrogenic differentiation effects of BMSCs after bFGF treatment were firstly studies in vitro, which was followed by transfecting the BMSCs with lentiviral vector encoding bFGF (BMSC-bFGF). The immunomodulatory effects of bFGF transfected BMSCs on macrophage polarization were assessed as well. Next, BMSCs or bFGF-transduced BMSCs were surgically injected into the TBI to observe their effects in vivo. Macroscopic observation, histological assessment, and biomechanical analysis were correspondingly performed to evaluate the regenerative efficacy of tendon-to-bone healing in a rat model.

RESULTS

In vitro experiments demonstrated that the lentivirus transfection of bFGF into BMSCs enhanced the proliferation and chondrogenic differentiation of BMSCs. More importantly, the bFGF transfected BMSCs also possessed excellent immunomodulatory capacity, which modulated macrophage polarization by promoting the transition of M0 macrophages towards M2 phenotype, thereby creating favorable microenvironment for the fast recovery of TBI injury. Accelerated regeneration of TBI injury was evidently observed in vivo, and promoted natural fibrocartilage differentiation was intimately correlated with the therapy of bFGF-transfected BMSCs.

CONCLUSION

This study demonstrated that the employment of bFGF-transfected BMSCs accelerated tendon-to-bone regeneration by regulation of immune responses and promotion of fibrocartilage formation, thereby improving its healing quality of TBI injury. These findings suggested a novel and promising strategy by transfecting the BMSCs with bFGF gene for the treatment of TBI injury.