Comparison of functional and histological outcomes after intralesional, intracisternal, and intravenous transplantation of human bone marrow-derived mesenchymal stromal cells in a rat model of spinal cord injury

Abstract

Few studies have compared methods of stem cell transplantation. The aim of the present study was to determine the optimal method of delivery of therapeutic stem cells in spinal cord injury (SCI). We compared functional and histologic outcomes after administration of human bone marrow stromal cells (BMSCs) by intralesional (ILT), intracisternal (ICT), and intravenous transplantation (IVT). A rat model of spinal cord injury was produced by dropping a 10-g weight, 2 mm in diameter, onto the exposed spinal cords of animals from a height of 25 mm. In each treatment group, 24 animals were randomly assigned for functional assessment and 24 for histologic examination. BMSCs (3 × 10(5), ILT; 1 × 10(6), ICT; 2 × 10(6), IVT) were transplanted 1 week after SCI in numbers determined in previous studies. Basso-Beattie-Bresnahan scoring was performed in all animals weekly for 6 weeks. Spinal cord specimens were obtained from eight animals in each group 2, 4, and 6 weeks after SCI. Viable BMSCs were counted in six sagittal sections from each spinal cord. All three treatment groups showed improved functional recovery compared to controls beginning 2 weeks after stem cell injection (P < 0.01). The ICT group showed the best functional recovery, followed by the ILT and IVT groups, respectively (P < 0.01). Histological analysis showed the largest number of viable BMSCs in the ILT group, followed by the ICT and IVT groups, respectively (P < 0.01). ICT may be the safest and most effective method for delivering stem cells and improving functional outcome in SCI when no limits are placed on the number of cells transplanted. As research on enhancing engraftment rates advances, further improvement of functional outcome can be expected.