Generation and Characterization of Mesenchymal Cell Lines for Osteorchondral Regeneration Researc

Abstract

Regeneration of bone and cartilage after trauma or age-related degenerative diseases remains a major clinical challenge. Due to their self-renewal and multi-differentiation potential, mesenchymal stromal cells (MSCs) are a promising cell source for bone and cartilage regeneration, but research on this field is impaired by MSCs’ predisposition to senescence when culture-expanded. Immortalization of MSCs allows them to bypass senescence, thus boosting the advances in MSC research. In this study, a method has been developed to immortalize MSCs derived from elderly donors by spinoculation of two immortalization genes: simian virus 40 large T antigen (SV40LT) and human telomerase reverse transcriptase (hTERT). Immortalized MSCs are phenotypically similar to primary MSCs and are able to differentiate to the three skeletal lineages, although their multi-differentiation potential is unbalanced towards the osteogenic pathway. Articular chondrocytes and synoviocytes can also be immortalized by the same method, but immortalized chondrocytes are metabolically different from primary articular chondrocytes. These immortalized cells can be useful as part of in vitro models of osteochondral regeneration and disease.