GSE109686
Cell transplantation strategies for acquired and inherited disorders of peripheral myelin
Objective: To investigate transplantation of rat Schwann cells or human iPSC-derived neural crest cells and derivatives into models of acquired and inherited peripheral myelin damage. Methods: Primary cultured rat Schwann cells labeled with a fluorescent protein for monitoring at various times after transplantation.  Human induced pluripotent stem cells (iPSCs) were differentiated into neural crest stem cells (NCSC), and subsequently toward a Schwann cell lineage via two different protocols.  Protocol 1 = treated with MesenPRO with Heregulin. Protocol 2 = coculture with iPSC-derived Motor Neurons. Cell types were characterized using flow cytometry, immunocytochemistry and transcriptomics. Rat Schwann cells and human iPSC-derivatives were transplanted into (i) nude rats pretreated with lysolecithin to induce demyelination or (ii) a transgenic rat model of dysmyelination due to PMP22 overexpression. Results: Rat Schwann cells transplanted into sciatic nerves with either toxic demyelination or genetic dysmyelination engrafted successfully, and migrated longitudinally for relatively long distances, with more limited axial migration.  Transplanted Schwann cells engaged existing axons and displaced dysfunctional Schwann cells to form normal appearing myelin.  Human iPSC-derived neural crest stem cells and their derivatives shared similar engraftment and migration characteristics to rat Schwann cells after transplantation, but did not further differentiate into Schwann cells or form myelin. Interpretation: These results indicate that cultured Schwann cells surgically delivered to peripheral nerve can engraft and form myelin in either acquired or inherited myelin injury, as proof of concept for pursuing cell therapy for diseases of peripheral nerve.  However, lack of reliable technology for generating human iPSC-derived Schwann cells for transplantation therapy remains a barrier in the field. Overall design: RNA-seq of iPSC-derived Neural Crest Stem Cells in three conditions: 1) untreated 2) treated with MesenPRO with Heregulin 3) cocultured with iPSC-derived Motor Neurons