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HESC- and hiPSC-derived Schwann cells are Molecularly and Functionally Equivalent

ABSTRACT: Establishing robust models of human myelinating Schwann cells is critical for studying peripheral nerve injury and disease. Stem cell differentiation has emerged as a key model of human cells and disease motivating development of Schwann cell differentiation protocols. Human embryonic stem cells (hESCs) are considered the ideal pluripotent cell but ethical concerns regarding their use have propelled the popularity of human induced pluripotent stem cells (hiPSCs). Given that the equivalence of hESCs and hiPSCs remains controversial, we sought to compare the molecular and functional equivalence of hESC- and hiPSC-derived Schwann cells generated with our previously reported protocol. We identified only modest transcriptome differences by RNA sequencing and insignificant proteome differences by antibody array. Additionally, both cell types comparably improved nerve regeneration and function in a chronic denervation and regeneration animal model. Our findings demonstrate that Schwann cells derived from hESCs and hiPSCs with our protocol are molecularly comparable and functionally equivalent.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208708 | GEO | 2024/05/29

REPOSITORIES: GEO

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Project description:The current understanding is that Schwann cell transplantation is ideal strategy for peripheral nerve regeneration instead of autograft. It is difficult to obtain the required amount of Schwann cells which are best transplant condition, and central nervous cells have been gained attention in recent years, but its regenerative mechanism remain unknown. Neural stem/progenitor cells (NSPC) can generate various type of neural lineage cells (NLCs), and NSPCs derived from pluripotent stem cells are promising cells for cell therapy for neurodegenerative diseases. However, more safe and accessible cell source of NSPCs are required. In this study, we aim to provide NLCs derived from human dental pulp stem cells (DPSCs), and reveal the mechanism involved in regeneration after NLCs transplantation into peripheral nerve defect. Here, characterization of NLCs, paracrine effects for endothelial cells and Schwann cells, in xenotransplant for rat 10mm sciatic nerve defect, the differentiation, the survival, and outcome of nerve regeneration were investigated. Induced NLCs consisted of neuronal lineage cells, astrocyte lineage cells, oligodendrocyte lineage cells, and neural crest lineage cells. Considering retrospectively, NLCs were possible derived from NSPCs. Microarray analysis revealed neural markers of primary embryological development were up-regulated in induced NLCs compared to DPSCs. Moreover, NLCs enhanced the activity of endothelial cells and Schwann cells by paracrine effects in vitro. Two weeks after transplantation, many transplanted NLCs differentiated into platelet-derived growth factor receptor alpha (PDGFRa) + oligodendrocyte progenitor cells (OPCs), and PDGFRa+/p75 neurotrophin receptor + Schwann cells derived from OPCs were observed. Twelve weeks after transplantation, NLCs promoted functional repair of peripheral nerve. A few human Schwann cells survived, but did not myelinate axon. These findings suggest that some of mechanism promoting for peripheral nerve regeneration by transplanted NLCs. Transplantation of NLCs derived from DPSCs into partial peripheral nerve defect may be widely used for further experiments.

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HESC- and hiPSC-derived Schwann cells are Molecularly and Functionally Equivalent

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