Search

Background Human central nervous system stem cells (HuCNS-SC) are multipotent adult stem cells with successful engraftment, migration, and region-appropriate differentiation after spinal cord injury (SCI). Objective To present data on the surgical safety profile and feasibility of multiple intramedullary perilesional injections of HuCNS-SC after SCI. Methods Intramedullary free-hand (manual) transplantation of HuCNS-SC cells was performed in subjects with thoracic (n = 12) and cervical (n = 17) complete and sensory incomplete chronic traumatic SCI. Results Intramedullary stem cell transplantation needle times in the thoracic cohort (20 M HuCNS-SC) were 19:30 min and total injection time was 42:15 min. The cervical cohort I (n = 6), demonstrated that escalating doses of HuCNS-SC up to 40 M range were well tolerated. In cohort II (40 M, n = 11), the intramedullary stem cell transplantation needle times and total injection time was 26:05 ± 1:08 and 58:14 ± 4:06 min, respectively. In the first year after injection, there were 4 serious adverse events in 4 of the 12 thoracic subjects and 15 serious adverse events in 9 of the 17 cervical patients. No safety concerns were considered related to the cells or the manual intramedullary injection. Cervical magnetic resonance images demonstrated mild increased T2 signal change in 8 of 17 transplanted subjects without motor decrements or emerging neuropathic pain. All T2 signal change resolved by 6 to 12 mo post-transplant. Conclusion A total cell dose of 20 M cells via 4 and up to 40 M cells via 8 perilesional intramedullary injections after thoracic and cervical SCI respectively proved safe and feasible using a manual injection technique.

Objective There is evidence that promoting the proliferation of endogenous neural stem cells in the spinal cord could be an effective strategy in the treatment of spinal cord injury. We studied this proliferation in a minimal injury rat model in the presence of epidermal growth factor and fibroblast growth factor-2. Methods Adult female Sprague Dawley rats were minimally injured at T8 and received the growth factors intrathecally by osmotic pump for either 3, 7, or 14 days beginning immediately after spinal cord injury. The infusions were made through a subarachnoid catheter connected to an osmotic minipump. Beginning at the time of injury, the rats received daily bromodeoxyuridine to label proliferating cells for determination of the labeling index. Results Significant differences were found in the labeling index between injured and non-injured rats. We concluded that minimal spinal cord injury from the stab injury and from the catheter itself increased the proliferation of ependymal region stem/progenitor cells. A minority (23.3%) of the rats developed proliferative lesions in association with the catheters alone, but the lesions were significantly larger and occurred in almost all (93.8%) rats receiving the mitogens, resulting in marked spinal cord compression. Conclusion The large proliferative growths in the epidermal growth factor and fibroblast growth factor-2-treated rats were unexpected and are indicative of the major effects of these mitogens. This suggests that considerable caution is required in devising therapeutic strategies directed toward mitogenic stimulation by growth factors delivered into the subarachnoid space. Further study is required to determine the appropriate and safe dosage of mitogens for potential use in spinal cord repair.