Bone marrow stromal cells (MSC) have shown great promise in improving outcome after spinal cord injury. There is, however, no efficient method to deliver them to the injury site. This is a small and focused research proposal that aims to develop and optimize protocols for delivering MSC via a Lumbar Puncture (LP) in a rat model of spinal contusion. LP delivery of MSC is a minimally invasive procedure that can be easily translated into human patients. Delivery of MSC via LP places cells into the cerebrospinal fluid (CSF), away from the hostile environment of the contused cord, and yet the circulating CSF offers MSC an opportunity to home into the injured site. Preliminary data and our published experience demonstrates that LP delivery is a feasible proposition. First, this project proposes to determine optimal protocols for performing LP transplantation of MSC for spinal cord contusion. Next, it uses these optimal protocols and compares their functional outcome with the standard method of direct parenchymal transplantation. Finally, it explores the possibility of performing autologous MSC transplantation (using syngeneic transplantation to mimic the autologous model) without any immunosuppression. Long-term cell survival experiments are also proposed to demonstrate lack of neoplastic potential and other toxicities with MSC transplantation into the central nervous system. All protocols will be validated by performing detailed histological and behavioral assessments. It is hoped that the results generated from this project will produce an innovative methodology for delivering stem cells in a minimally invasive way. This novel technique will lead to significant breakthroughs in translating basic stem cell research into the clinic and will facilitate earlier clinical trials because of the minimally invasive nature of this technique.
| Paul, Courtney; Samdani, Amer F; Betz, Randal R et al. (2009) Grafting of human bone marrow stromal cells into spinal cord injury: a comparison of delivery methods. Spine (Phila Pa 1976) 34:328-34 |
| Neuhuber, Birgit; Swanger, Sharon A; Howard, Linda et al. (2008) Effects of plating density and culture time on bone marrow stromal cell characteristics. Exp Hematol 36:1176-85 |
| Neuhuber, Birgit; Barshinger, Alissa L; Paul, Courtney et al. (2008) Stem cell delivery by lumbar puncture as a therapeutic alternative to direct injection into injured spinal cord. J Neurosurg Spine 9:390-9 |
