Regenerative effects of human embryonic stem cell‐derived neural crest cells for treatment of peripheral nerve injury

• Published in: Journal of tissue engineering and regenerative medicine Vol. 12; no. 4; pp. e2099 - e2109
• Main Authors: Jones, Iwan, Novikova, Liudmila N., Novikov, Lev N., Renardy, Monika, Ullrich, Andreas, Wiberg, Mikael, Carlsson, Leif, Kingham, Paul J.
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01.04.2018; John Wiley and Sons Inc
• Subjects: 2007; Animals; artificial nerve graft; Axonogenesis; Biodegradability; Biodegradation; Biological activity; Biological effects; Cell Line, Tumor; Conditioning; Dorsal root ganglia; Embryo cells; Embryos; Female; Gene expression; Grafts; Heterografts; human embryonic stem cells; Human Embryonic Stem Cells - metabolism; Humans; Injury prevention; NATURE BIOTECHNOLOGY; Nerve Regeneration; Nervous system; Neural crest; Neural Crest - metabolism; Neural Crest - transplantation; neural crest cells; Neural stem cells; P1468; P95 e Gabsang; peripheral nerve injuries; Peripheral Nerve Injuries - therapy; Peripheral nervous system; Rats; Rats, Sprague-Dawley; Regeneration; Regenerative medicine; ripheral nervous system; Sciatic nerve; Sciatic Nerve - injuries; Sciatic Nerve - physiology; Spinal cord; Stem cell transplantation; Stem cells; Surgery; Tissue engineering; Trophic factors; V25; V314B; VELOPMENTAL EVOLUTION; neural crest cells; peripheral nervous system; artificial nerve graft; peripheral nerve injuries; human embryonic stem cells
• ISSN: 1932-6254; 1932-7005; 1932-7005
• DOI: 10.1002/term.2642

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.