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

被引:37
作者
Jones, Iwan [1 ,2 ]
Novikova, Liudmila N. [2 ]
Novikov, Lev N. [2 ]
Renardy, Monika [3 ]
Ullrich, Andreas [3 ]
Wiberg, Mikael [2 ,4 ]
Carlsson, Leif [1 ]
Kingham, Paul J. [2 ]
机构
[1] Umea Univ, Umea Ctr Mol Med, Umea, Sweden
[2] Umea Univ, Dept Integrat Med Biol, Lab Neural Repair & Cellular Therapy, S-90187 Umea, Sweden
[3] ITV Denkendorf Prod Serv GmbH, Denkendorf, Germany
[4] Umea Univ, Dept Surg & Perioperat Sci, Hand & Plast Surg, Umea, Sweden
基金
瑞典研究理事会;
关键词
artificial nerve graft; human embryonic stem cells; neural crest cells; peripheral nerve injuries; peripheral nervous system; SENSORY NEURONS; SCHWANN-CELLS; NEUROTROPHIC FACTOR; GROWTH; DIFFERENTIATION; MIGRATION; CONDUIT; REPAIR; AXON; TRANSPLANTATION;
D O I
10.1002/term.2642
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:E2099 / E2109
页数:11
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