BACKGROUND: Although previous studies have indicated that transplantation of marrow stromal cells (MSCs) has enhanced axonal regeneration and improved motor dysfunction induced by spinal cord injury. However, it is still unclear how transplanted MSCs promoted axonal regeneration and the relationship of transplanted cells and regenerated axons.OBJECTIVE: By immunofluorescence and immunoelectron microscopy, this study sought to elucidate the mechanism of promoting axonal sprouting following transplantation of MSCs into a completely transected spinal cord.DESIGN, TIME AND SETTING: The in vivo cytology randomized controlled animal experiment was performed at the Department of Anatomy of National University of Singapore from March 2006 to June 2007.MATERIALS: MSCs were isolated and purified from a Wistar neonatal rat. Model of completely transected spinal cord injury was established by transection at T_(10) segment with asepsis technique using 36 clean adult female Wistar rats.METHODS: MSCs were subcultured and purified. Thirty-six adult female Wistar rats were randomly divided into transplanted and control groups, with 18 animals in each group. Following 9 days of completely transected spinal cord injury, rats in the transplanted group were injected with MSCs (1×10~(11)/L), 5 μL in the defect region and 2.5 μL in 1 mm upper and lower the defect region. Rats in the control group were infused with an equal volume of DMEM, at the speed of 1 μL/min.MAIN OUTCOME MESSURES: Survival and differentiation of transplanted MSCs; Regeneration of axon and survival of host-derived nestin-, NF200-, GFAP-, and CNP-positive cells in control and transplanted groups; Relationship of regenerated axon and CNP-positive cells RESULTS: Two weeks after transplantation, a large number of CFDA-SE labeled MSCs were detected in the lesion site. Survival transplanted cell number was decreased over time. Abundant 0×42-positive phagocytes/activated microglia and cavity might affect the survival of transplanted cells. The number of MSCs was decreased, but MSC transplantation could promote axonal regeneration in the lesion site, and enhance the survival of host-derived nestin-, NF200-, GFAP-, and CNP-positive cells in lesion site, and host-derived CNP-positive cells and Schwann cells provided structural support to regenerated axons and promote their remyelination in spinal cord injury.CONCLUSION: Transplantation of MSCs enhances survival of host-derived CNP- positive cells and Schwann cells, and which may provide structural support to regenerated axons and promote their remyelination in spinal cord injury.