Pluripotent Stem Cells for Schwann Cell Engineering

Ma, Ming-San; Boddeke, Erik; Copray, Sjef

doi:10.1007/s12015-014-9577-1

Cited by 34 publications

(26 citation statements)

References 172 publications

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“…Several different protocols have been employed to obtain SCs from induced pluripotent stem cells, and most of them require several weeks of in vitro differentiation (Wang et al ., ; Ma et al ., ). It is also important to note that the protocol that we employed was originally developed and optimized for rodent cultures.…”

Section: Discussionmentioning

confidence: 97%

Human Schwann‐like cells derived from adipose‐derived mesenchymal stem cells rapidly de‐differentiate in the absence of stimulating medium

Faroni

Smith

Lü

et al. 2015

Eur J of Neuroscience

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Finding a viable cell-based therapy to address peripheral nerve injury holds promise for enhancing the currently suboptimal microsurgical approaches to peripheral nerve repair. Autologous nerve grafting is the current gold standard for surgical repair of nerve gaps; however, this causes donor nerve morbidity in the patient, and the results remain unsatisfactory. Transplanting autologous Schwann cells (SCs) results in similar morbidity, as well as limited cell numbers and restricted potential for expansion in vitro. Adipose-derived stem cells (ASCs), 'differentiated' towards an SC-like phenotype in vitro (dASCs), have been presented as an alternative to SC therapies. The differentiation protocol stimulates ASCs to mimic the SC phenotype; however, the efficacy of dASCs in nerve repair is not yet convincing, and the practicality of the SC-like phenotype is unproven. Here, we examined the stability of dASCs by withdrawing differentiation medium for 72 h after the full 18-day differentiation protocol, and measuring changes in morphology, gene expression, and protein levels. Withdrawal of differentiation medium from dASCs resulted in a rapid reversion to stem cell-like characteristics. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay analyses demonstrated a significant reduction in gene and protein expression of growth factors that were expressed at high levels following 'differentiation'. Therefore, we question the relevance of differentiation to an SC-like phenotype, as withdrawal of differentiation medium, a model of transplantation into an injured nerve, results in rapid reversion of the dASC phenotype to stem cell-like characteristics. Further investigation into the differentiation process and the response of dASCs to an injured environment must be undertaken prior to the use of dASCs in peripheral nerve repair therapies.

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Section: Discussionmentioning

confidence: 97%

Human Schwann‐like cells derived from adipose‐derived mesenchymal stem cells rapidly de‐differentiate in the absence of stimulating medium

Faroni

Smith

Lü

et al. 2015

Eur J of Neuroscience

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“…Future improvements to the currently described disease model could be the addition of a coculture with iPSC-derived Schwann cells, thereby providing in vitro myelination and formation of nodes of Ranvier. 3,50,51 Nevertheless, in its current form, the model recapitulates the progressive, irreversible axonal damage, which can in part be alleviated by immunoglobulin treatment, mimicking clinical treatment response to immunoglobulins. [52][53][54] Overall, our results demonstrate that human iPSCderived MNs represent a novel disease model for MMN, and show for the first time that IgM anti-GM1 antibodies are pathogenic to human MNs.…”

Section: Discussionmentioning

confidence: 99%

Autoantibody pathogenicity in a multifocal motor neuropathy induced pluripotent stem cell–derived model

Harschnitz

Berg

Johansen

et al. 2016

Annals of Neurology

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“…Several methods have been published to differentiate human iPSCs into cells which possess markers of Schwann cells, typically as a minor component of a neuronal differentiation, or directed from NCSCs to generate cultures enriched in Schwann precursors. 37 An earlier report demonstrated that prolonged culture of NCSCs in mesenchymal stem cell medium supplemented with heregulin-b1 (a key instructive signal for Schwann cell development) generated cells expressing markers of Schwann cell precursors and found that these cells could form myelin after coculture with sensory neurons. 29 Utilizing the "MESH" protocol (MesenPRO with heregulin), we attempted to differentiate Schwann cell precursors from human NCSCs generated above (Fig.…”

Section: Characterization Of Putative Ipsc-derived Schwann Cell Precumentioning

confidence: 99%

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

Muhammad

Kim

Epifantseva

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo investigate transplantation of rat Schwann cells or human iPSC‐derived neural crest cells and derivatives into models of acquired and inherited peripheral myelin damage.MethodsPrimary 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, and subsequently toward a Schwann cell lineage via two different protocols. Cell types were characterized using flow cytometry, immunocytochemistry, and transcriptomics. Rat Schwann cells and human iPSC derivatives were transplanted into (1) nude rats pretreated with lysolecithin to induce demyelination or (2) a transgenic rat model of dysmyelination due to PMP22 overexpression.ResultsRat 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.InterpretationThese 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.

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Pluripotent Stem Cells for Schwann Cell Engineering

Cited by 34 publications

References 172 publications

Human Schwann‐like cells derived from adipose‐derived mesenchymal stem cells rapidly de‐differentiate in the absence of stimulating medium

Human Schwann‐like cells derived from adipose‐derived mesenchymal stem cells rapidly de‐differentiate in the absence of stimulating medium

Autoantibody pathogenicity in a multifocal motor neuropathy induced pluripotent stem cell–derived model

Cell transplantation strategies for acquired and inherited disorders of peripheral myelin

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