Preclinical Studies on Mesenchymal Stem Cell-Based Therapy for Growth Plate Cartilage Injury Repair

Abstract

In the last two decades, there has been a strong interest in searching for biological treatments for regeneration of injured growth plate cartilage and prevention of its bony repair. Various means have been tried, including implantation of chondrocytes, mesenchymal stem cell (MSC), together with exogenous growth factor and scaffolds, and gene therapy. However, with the lack of success with chondrocytes, more research has focussed on MSC-based treatments. In addition to circumvent limitations with MSC-based treatments (including cell harvest-associated morbidity, difficulties/time/cost involved in MSC isolation and ex vivo expansion, and potential disease transmission), mobilising endogenous MSCs to the growth plate injury site and enhancing in situ regeneration mechanisms would represent an alternative attractive approach. Further studies are required to investigate the potential particularly in large animal models or clinical setting of the ex vivo MSC approach and the feasibility of the endogenous MSC in situ approach in growth plate regeneration.

Fibronectin and stem cell differentiation – lessons from chondrogenesis

“…There was some success in using mesenchymal stem cells to repair injured articular cartilage in animal models (see, for example, Wakitani et al, 1994). However, optimizing the microenvironment with appropriate ECM proteins and soluble factors to promote chondrogenic differentiation of implanted stem cells has been a challenge (Chung et al, 2011). One approach is to use polymer-based, biodegradable, three-dimensional scaffolds that mimic the mesenchymal ECM in composition and stiffness.…”

Current concepts: tissue engineering and regenerative medicine applications in the ankle joint

“…Through direct cell-to-cell interactions or by secreting a number of different proteins, MSCs can promote the endogenous regenerative mechanisms still present in an arthritic joint [101]. …”

The effect of temporal manipulation of transforming growth factor beta 3 and fibroblast growth factor 2 on the derivation of proliferative chondrocytes from mensenchymal stem cells—A study monitored by quantitative reverse transcription polymerase chain reaction and molecular beacon based nanosensors

“…These fractures not only impair the growth process of growth plate, but also cause vascularization and mineralization at injury site, eventually resulting in the formation of bony bridge . Current clinical treatments, such as the excision of the bony bridge and insertion of interposition materials, osteotomies, or limb lengthening, are only managing the injury complications, rather than facilitating functional restoration . For example, limb lengthening is commonly performed to correct large limb length discrepancies in the presence of growth plate arrest.…”

“…For example, limb lengthening is commonly performed to correct large limb length discrepancies in the presence of growth plate arrest. This treatment mainly uses external yet highly invasive means to replace the function of growth plate instead of restoring its function …”