Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells

Abstract

OBJECTIVE: Spinal cord injury results in loss of neurons, degeneration of axons, formation of glial scar, and severe functional impairment. Human umbilical cord mesenchymal stem cells can be induced to form neural cells in vitro. Thus, these cells have a potential therapeutic role for treating spinal cord injury. DESIGN AND SETTING: Rats were randomly divided into three groups: sham operation group, control group, and human umbilical cord mesenchymal stem cell group. All groups were subjected to spinal cord injury by weight drop device except for sham group. SUBJECTS: Thirty-six female Sprague-Dawley rats. INTERVENTIONS: The control group received Dulbecco's modified essential media/nutrient mixture F-12 injections, whereas the human umbilical cord mesenchymal stem cell group undertook cells transplantation at the dorsal spinal cord 2 mm rostrally and 2 mm caudally to the injury site at 24 hrs after spinal cord injury. MEASUREMENTS: Rats from each group were examined for neurologic function and contents of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and neurotrophin-3. Survival, migration, and differentiation of human umbilical cord mesenchymal stem cells, regeneration of axons, and formation of glial scar were also explored by using immunohistochemistry and immunofluorescence. MAIN RESULTS: Recovery of hindlimb locomotor function was significantly enhanced in the human umbilical cord mesenchymal stem cells grafted animals at 5 wks after transplantation. This recovery was accompanied by increased length of neurofilament-positive fibers and increased numbers of growth cone-like structures around the lesion site. Transplanted human umbilical cord-mesenchymal stem cells survived, migrated over short distances, and produced large amounts of glial cell line-derived neurotrophic factor and neurotrophin-3 in the host spinal cord. There were fewer reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the human umbilical cord-mesenchymal stem cell group than in the control group. CONCLUSIONS: Treatment with human umbilical cord mesenchymal stem cells can facilitate functional recovery after traumatic spinal cord injury and may prove to be a useful therapeutic strategy to repair the injured spinal cord.