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. 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. 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. 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.