Basic and Translational Research
Skeletal Regeneration and Repair
Skeletal Stem Cell and Microenvironment (Niche)
As we demonstrated in mice, we have also identified conditions for inducing human SSC and human bone and cartilage formation from human adipose tissue. Inducing SSC formation in situ with soluble factors and subsequently regulating the SSC niche to specify its differentiation towards bone, cartilage, or stromal cells would represent a paradigm shift in the therapeutic regeneration of skeletal tissues. Conversely, it is important to characterize the biology of SSC inducible cells and their potential role in pathological heterotropic ossification. This research seeks to address key questions regarding the identify of the SSC inducible cells present in human adipose tissue and the genetic mechanisms underlying plasticity in their cell fates and the process of re-specification into induced SSCs (iSSCs). We are also examining the biological differences between iSSCs and endogenous SSCs isolated from skeletal tissues in response to signaling that promote expansion and lineage commitment of SSC.
Injury and disease of skeletal tissue including bone and cartilage is an enormous, and growing medical burden. Our group has recently identified a self-renewing skeletal stem cell (mSSC) in mice that generates bone, cartilage and hematopoietic-supportive niche stromal cells (Cell, 2015). We then molecularly characterized the stem cell micro-environment (niche) of mSSC and identified specific signaling pathways guiding SSC expansion and differentiation towards bone or cartilage lineages. Through the lens of SSC biology, we observe that normal SSC activity is essential for normal skeletal homeostasis and regeneration (PNAS, 2015) while diminished or defective SSC activity underlies osteoporosis in aging and poor fracture healing in Type2 Diabetes Mellitus (STM, submitted). These studies define a pressing clinical need for identifying new methods to amplify SSC numbers and SSC activity in treating injuries or diseases of the skeletal system. To speed clinical translation for our findings on mSSC, we have now succeeded in isolating and purifying human skeletal stem cells (hSSC) that are the functional equivalent of mouse SSC.