Dosing parameters for grafting human neural stem cells into sites of spinal cord injury.
Publication Year:
2025
PubMed ID:
40992614
Funding Grants:
Public Summary:
This study evaluated the effects of transplanting different amounts of neural stem cells in a site of spinal cord in rodents. The study helps to establish what the optimal dose of cells in future clinical trials.
Scientific Abstract:
Grafts of neural stem cells into sites of spinal cord injury (SCI) in animal models support functional improvement by forming new synaptic relays across the lesion site. Efficacy has been demonstrated in mouse, rodent and rhesus monkey models of SCI after both thoracic and cervical level injury. In preparation for the initiation of clinical trials, it is important to establish the minimum effective dose and maximal tolerated dose of neural stem cells implanted into lesion sites. Accordingly, we grafted our human embryonic stem cell-derived spinal cord neural progenitor cells into sites of rat thoracic spinal cord contusion at five different doses ranging from 10,000 to 400,000 cells/mul. 12-weeks post-grafting, spinal cord tissue was assessed for graft filling, neuronal differentiation, graft axonal outgrowth and host axonal ingrowth. We now report that in rats; the minimum effective dose is 100,000 cells/mul and the maximum tolerated dose is 400,000 cells/mul. These cell concentrations constitute a potential cell dose range for testing in human clinical trials.