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Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
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2018 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 12, no 4, p. E2099-E2109Article in journal (Refereed) Published
Abstract [en]

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair.

Place, publisher, year, edition, pages
2018. Vol. 12, no 4, p. E2099-E2109
Keywords [en]
artificial nerve graft, human embryonic stem cells, neural crest cells, peripheral nerve injuries, ripheral nervous system, VELOPMENTAL EVOLUTION, V314B, P95 e Gabsang, 2007, NATURE BIOTECHNOLOGY, V25, P1468
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-147466DOI: 10.1002/term.2642ISI: 000430395400024PubMedID: 29327452OAI: oai:DiVA.org:umu-147466DiVA, id: diva2:1210267
Funder
Swedish Research Council, 2014-2306Available from: 2018-05-28 Created: 2018-05-28 Last updated: 2018-06-09Bibliographically approved

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Jones, IwanNovikova, Liudmila N.Novikov, Lev N.Wiberg, MikaelCarlsson, LeifKingham, Paul J.

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Jones, IwanNovikova, Liudmila N.Novikov, Lev N.Wiberg, MikaelCarlsson, LeifKingham, Paul J.
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Umeå Centre for Molecular Medicine (UCMM)Department of Integrative Medical Biology (IMB)Department of Surgical and Perioperative Sciences
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Journal of Tissue Engineering and Regenerative Medicine
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