Transdifferentiation of human fibroblasts into chondrocytes

Abstract

The present study is a proof-of-principle study that proposes an approach to transdifferentiate human neonatal dermal fibroblasts into human chondrocytes. Transdifferentiation is a process by which one mature differentiated cell can become another mature cell without going through a pluripotent state (Slack, 2007; Okada, 1991). Neonatal dermal fibroblasts are chosen because they are abundant, free of ethical concern, lack of immunogenicity (they have undeveloped HLA tissue markers and do not express HLA-DR markers (Kern, 2001; Rider et al., 2008)) and they have no risk of tumor transformation. Cell-specific microenvironment instead of chemically defined culture medium will be used for transdifferentiation. Significance of this study is that it presents a proof-of-concept for producing certain cell types that no known factors have been currently identified or reported for the production of that cell type. This study aims to decellularize rabbit chondrocytes deposited matrix and to repopulate the acellular matrix with human neonatal dermal fibroblasts. Histological analysis showed that rabbit chondrocytes encapsulated in collagen microspheres were able to produce a GAG-rich and type II collagen-rich extracellular matrix. After removing all rabbit chondrocytes with decellularization detergents, human fibroblasts were seeded onto the acellular microspheres. Histological analysis showed that the seeded human fibroblasts were able to transdifferentiate into human chondrocytes. Mass spectrometry was also done. It is revealed that collagen XII was deposited in rabbit chondrocytes microspheres and it was still retained after treatment of decellularization reagents. So, collagen XII might be a key factor in inducing the transdifferentiation of human fibroblasts into chondrocytes.