Therapeutic delivery of placental stem cells to modulate vasculature and promote fracture repair (342.6)

Abstract

Blood supply to a bone fracture is a critical determinant of the rate and extent of healing. Therapies designed promote bone healing by stimulating angiogenesis have been proposed for a long time, yet, to date no effective treatments are available. In this work, we capitalize on a transient process that modifies the vasculature during pregnancy to support the developing fetus. Placental progenitors, trophoblast stem cells (TSCs), promote vasculogenesis in response to fetal hypoxia by physically remodeling the maternal arterioles and secreting angiogenic factors to generate a high volume, low pressure fluid exchange. We hypothesize that the therapeutic application of TSCs will promote vascular remodeling and enhance fracture healing. Our data shows that TSCs injected to non‐stabilized murine fractures engraft into the vasculature and enhance the local blood supply. Furthermore, injection of TSCs increased the volume of the cartilage callus 7‐days post fracture, leading to more bone after 14‐days of healing. To our knowledge, this is the first study evaluating the therapeutic potential of trophoblasts. Our results have the potential to enhance clinical outcomes in skeletal trauma, where there is often poor vascular perfusion. Importantly, this work may also have a significant impact on the broader field of regenerative medicine, since loss of organ function is often intimately tied to compromised vascularity.Grant Funding Source: NIH ‐ NRSA F32