Pesquisa e inovação biomédica avançada

Targeting twist to promote stem cell based cartilage repair

Yufeng Dong, Shane Barton and Yuping Wang

Rapid induction of Mesenchymal stem cells (MSCs) chondrogenic differentiation during therapeutic transplantation remains extremely challenging. Here the author undertook a study to determine if twist1 inhibition by shRNA could be utilized to accelerate human Placenta-derived MSCmediated cartilage repair in a mouse cartilage defect model. Our data clearly indicated that silencing twist1 significantly enhanced chondrogenesis by showing increased alcian blue staining enhanced Col-II expression when compared to control wild type PMSCs. Importantly, the in vivo transplantation of twist1 deficient PMSCs into knee joint cartilage defects had a significantly enhanced cartilage formation by showing stronger alcian blue and Col-II staining in cartilage defect area. Finally, the PCR data further confirmed an increased expression of chondrogenic markers Sox9, Col-II and aggrecan in knee joint tissue with transplantation of twist1 deficient PMSCs. Collectively; these findings demonstrate that PMSCs are a favourable cell source for cartilage repair and silencing transcript factor twist1 could accelerate PMSC differentiation into chondrocyte under the cartilage micro-environment in vivo.