Increase of chondrogenic potentials in adipose-derived stromal cells by co-delivery of type I and type II TGFβ receptors encoding bicistronic vector system

Abstract

Stem cell therapy has been developing rapidly as a potential cure for repairing or regenerating the functions of diseased organs and tissues. Adipose-derived stromal cells (ASCs) are an attractive cell source for stem cell therapy because they can be isolated easily from fat tissue in significant numbers and exhibit multiple differentiation potential under appropriate in vitro culture conditions. However, ASCs derived from individual donors can show wide variations in differentiation potential. In addition, the regulatory mechanisms underlying stem cell differentiation remain unclear. Transforming growth factor β (TGFβ) is a well-known ASC chondrogenic differentiation factor that stimulates ASC signaling pathways by activating transmembrane type I and type II receptors. We hypothesized that the chondrogenic differentiation potential of ASCs is dependent upon the expression of TGFβ receptors and could be improved by the co-delivery of type I (TGFβRI) and type II (TGFβRII) TGFβ receptors. To prove this, heterogeneity within the chondrogenic potential of ASCs isolated from 10 donors was examined and their susceptibility to TGFβ during the process of chondrogenic differentiation investigated. In addition, the results showed that co-delivery of the TGFβRI and TGFβRII genes increased the expression of TGFβ receptor signaling in ASCs with low chondrogenic potential, resulting in increased chondrogenic differentiation. Monitoring and delivering TGFβRI and TGFβRII may, therefore, be a powerful tool for predicting the differentiation potential of stem cells and for enhancing their differentiation capacity prior to stem cell transplantation.