BACKGROUND: Spinal cord injury (SCI) is a devastating and irreversible event, and much research using fibroblast growth factor-2 (FGF-2) has been performed to test its capacity to blunt the effects of SCI as well as to provide an environment conducive for SCI repair. METHODS: We tested how the in vitro release of FGF-2 from heparin-conjugated poly(L-lactide-co-glycolide) (PLGA)-conjugated nanospheres (HCPNs) affected the growth of human bone marrow-derived mesenchymal stem cells (hBMSCs), as well as the effects of their co-transplantation in an animal model of SCI. RESULTS: Our results showed that sustained, long-term release of FGF-2 from HCPNs significantly increased hBMSCs proliferation in vitro, and that their co-transplantation following rat SCI lead to increased functional improvement, a greater amount of hBMSCs surviving transplantation, and a greater density of neurofilament-positive cells in the injury epicenter. CONCLUSION: These results suggest a proliferative, protective, and neural inductive potential of FGF-2 for transplanted hBMSCs, as well as a possible role for sustained FGF-2 delivery along with hBMSCs transplantation in the injured spinal cord. Future studies will be required to ascertain the safety FGF-2-containing HCPNs before clinical application.
BACKGROUND:Spinal cord injury (SCI) is a devastating and irreversible event, and much research using fibroblast growth factor-2 (FGF-2) has been performed to test its capacity to blunt the effects of SCI as well as to provide an environment conducive for SCI repair. METHODS: We tested how the in vitro release of FGF-2 from heparin-conjugated poly(L-lactide-co-glycolide) (PLGA)-conjugated nanospheres (HCPNs) affected the growth of human bone marrow-derived mesenchymal stem cells (hBMSCs), as well as the effects of their co-transplantation in an animal model of SCI. RESULTS: Our results showed that sustained, long-term release of FGF-2 from HCPNs significantly increased hBMSCs proliferation in vitro, and that their co-transplantation following rat SCI lead to increased functional improvement, a greater amount of hBMSCs surviving transplantation, and a greater density of neurofilament-positive cells in the injury epicenter. CONCLUSION: These results suggest a proliferative, protective, and neural inductive potential of FGF-2 for transplanted hBMSCs, as well as a possible role for sustained FGF-2 delivery along with hBMSCs transplantation in the injured spinal cord. Future studies will be required to ascertain the safety FGF-2-containing HCPNs before clinical application.