In Utero Treatment of Myelomeningocele with Placental Mesenchymal Stromal Cells – Selection of an Optimal Cell Line in Preparation for Clinical Trials.

Background We developed a cell culture assay in order to determine if different lines of placenta mesenchymal stromal cells (PMSCs) can protect cultured neurons from dying when a toxin was administered to the neurons. We then examined if these same PMSC cell lines would have the same neuro protective effect in a fetal lamb model of spina bifida. Methods PMSC lines were created following culture of three different early age human placentas. The lines were labeled as A, B, and C. Their ability to protect dying neurons in a cell culture model was assessed. Spina bifida was created in 28 fetal lambs, and the lambs were repaired with PMSCs seeded on a clinical grade scaffold from each cell line. The number of lambs treated with each different cell line were: 6 with Line A , 7 with Line B, 5 with Line C, and 10 lambs did not receive PMSCs. The lambs motor function post birth was scored with the establish Sheep Locomotor Rating (SLR) scale. A score of 15 denotes normal motor function, while a score of 0 indicates complete hindlimb paralysis. Results Cell culture, Line A and B had a higher neuro protective effect than no PMSCs. Line C did not have a higher neuro protective effect than no PMSCs. Lambs treated with Line A and B had higher motor function scores than lambs that were treated with Line C or with no PMSCs. Conclusion The cell culture model used to assess a PMSC line’s ability to protect dying neurons in culture can provide insight on the same cell line’s ability to protect neurons in a lamb spina bifida model. Thus, the cell culture model can help predict if a PMSC line will aid in restoring motor function in human spina bifida.