| 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.
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