Abstract
Mesenchymal stem cells (MSCs) have been long studied for their role in skeletal development. MSCs are unique in adult physiology in that they exhibit pluripotency and differentiate into cells that can evolve into various skeletal tissue as a result have been extensively employed as a viable alternative to terminally differentiated cells in engineering of cartilage and bone tissue ex vivo and in vivo. In spite of decades of effort in this direction, our understanding of what drives MSC fate choices is rather narrow in that it places heavy emphasis on a role for morphogens and cytokines (TGF-beta super family, FGF-2). In recent years it has become evident that MSCs also play an important role in wound healing, immunomodulation (immune suppression) and in tumour progression. However, what becomes of an MSC when it arrives at or exits an environment is less understood. We hypothesize that activation of differentiation programs in MSCs have an autocrine and paracrine component involving interplay between MSC-MSC (cell-cell contact) and MSC-(environment), and in this signalling paradigm the biophysical aspects of their microenvironment play a dominant role. We have tested this premise in several aspects of MSC behaviour (proliferation, migration, differentiation, chondrogenesis) and have gathered compelling evidence for biophysics and mechanobiology in MSC fate decisions. This talk will present some of our latest findings in this broad arena.
