Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.
Laboratory of Neural Repair and Cellular Therapy, Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
J Tissue Eng Regen Med. 2018 Apr;12(4):e2099-e2109. doi: 10.1002/term.2642. Epub 2018 Feb 18.
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.
手术干预是周围神经损伤后的当前金标准治疗方法。然而，这种方法有其局限性，运动和感觉方式的完全恢复通常仍然不完整。因此，开发能够补充或替代当前手术的人工神经移植物至关重要。人工移植物的一个重要组成部分是可生物降解的导管和移植细胞，它们在再生过程中提供营养支持。神经嵴细胞是有前途的支持细胞候选物，因为它们是许多周围神经系统谱系的亲本群体。在这项研究中，从人类胚胎干细胞中分化出了神经嵴细胞。分化后的细胞表现出典型的星状形态和与天然神经嵴相当的蛋白质表达特征。从分化细胞中收获的条件培养基含有一系列具有生物活性的营养因子，并能够刺激体外神经突生长。将分化的神经嵴细胞接种到可生物降解的神经导管中，并在大鼠坐骨神经损伤模型中评估其再生潜力。在接种了分化的神经嵴细胞的导管整个宽度上观察到了强大的再生前沿。此外，在从移植动物中收获的背根神经节和脊髓节段中观察到几个与再生相关的基因的上调。我们的结果表明，分化的神经嵴细胞具有生物活性，并提供营养支持以刺激周围神经再生。因此，分化的神经嵴细胞是有前途的支持细胞候选物，有助于周围神经修复。
