This technology identifies small molecule compounds that specifically induce perivascular tendon stem cell differentiation for the treatment of tendon injuries.
Tendon injuries account for almost half of the reported musculoskeletal injuries in the United States, and as such, represent an acute healthcare burden on the healthcare system. Current stem cell-based strategies for tissue regeneration involve the ex vivo manipulation and transplantation back into the patient, an approach that has encountered barriers such as immune rejection, pathogen transmission, and high costs. An alternative strategy is to directly differentiate endogenous cells such as perivascular tendon stem cells (PTSCs), a small population of multipotent cells that are critical to tendon healing and regeneration, but such therapies are limited by the challenges associated with biologic therapeutics. As such, there is a need for small molecule compounds that can induce the differentiation of endogenous stem cells for tendon cell regeneration.
This technology identifies small molecule compounds that induce the differentiation of PTSCs into tendon-like cells. This technology is based on the finding that connective tissue growth factors (CTGFs) induce tenogenic differentiation of PTSCs via the FAK and ERK1/2 pathways, consequently leading to tendon regeneration in rats. By screening FAK and ERK1/2 agonists in cultured rat PTSCs, two compounds, oxotremorine M (Oxo-M) and PPBP maleate (4-PPBP), were identified that dramatically increased tendon-related gene expression when administered together. Importantly, the combination therapy induces tenogenic differentiation of PTSCs with a similar level of efficiency compared to CTGFs. As such, concurrent treatment with Oxo-M and 4-PPBP may provide a simple, low-cost method for treating tendon injuries. This technology has been validated in vitro by direct differentiation of cultured rat PTSCs.
IR CU16159
Licensing Contact: Cynthia Lang
