During the past reporting period, we have achieved on time completion of milestones 1-3, and Study 1 of milestone 5, as expected. Specifically, we have established master and working cell banks of our placental-derived stem cells (PMSCs) using protocols and reagents that are compliant with current good manufacturing practice. We have also demonstrated that the PMSCs express common stem cell markers and are karyotypically normal. The stem cells have been evaluated to assure purity, viability, and cytokine secretion profile. We have also successfully converted from a research grade extracellular matrix vehicle to an FDA-approved clinical grade vehicle. The applied stem cells have been shown to retain both their potency and stability on the new vehicle. We have determined the total number of PMSCs that can be seeded onto the FDA approved vehicle and shown that the cells secret more than sufficient amounts of neuroprotective growth factors in this vehicle. Finally, an assay was developed that demonstrates, the neuroprotective capability of the cells in the FDA approved vehicle using a cultured damaged neuronal cell line.
The placental stem cell seeded clinical grade vehicle combination product was then used for repair of the established fetal lamb model of spina bifida with excellent results thus far. To date of the fetal lambs repaired with the combination product 5 of 8 were able to walk at birth, which is consistent with our preclinical findings in the research grade cell product. Histopathologic analysis of the spinal cords again shows preservation of large neurons in lambs repaired with the combination product compared to no stem cell controls. Dose optimization studies are currently ongoing in a rodent model of chemically-induced spina bifida. Once complete, further dose optimization and efficacy studies will be performed in the large animal model as well. We anticipate that the final two milestones will be completed within the study time frame taking the project to IND readiness.