Francis Nicola L, Bennett Neal K, Halikere Apoorva, Pang Zhiping P, Moghe Prabhas V
Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, New Jersey 08854, United States.
Department of Neuroscience and Cell Biology, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, New Jersey 08901, United States.
ACS Biomater Sci Eng. 2016 Jun 13;2(6):1030-1038. doi: 10.1021/acsbiomaterials.6b00156. Epub 2016 May 4.
While cell transplantation presents a potential strategy to treat the functional deficits of neurodegenerative diseases or central nervous system injuries, the poor survival rate of grafted cells is a major barrier to effective therapeutic treatment. In this study, we investigated the role of a peptide-based nanofibrous scaffold composed of the self-assembling peptide RADA16-I to support the reprogramming and maturation of human neurons and to transplant these neurons . The induced human neurons were generated via the single transcriptional factor transduction of induced pluripotent stem cells (iPSCs), which are a promising cell source for regenerative therapies. These neurons encapsulated within RADA16-I scaffolds displayed robust neurite outgrowth and demonstrated high levels of functional activity compared to that of 2-D controls, as determined by live cell calcium imaging. When evaluated as a transplantation vehicle for adherent, functional networks of neurons, monodisperse RADA16-I microspheres significantly increased survival (over 100-fold greater) compared to the conventional transplantation of unsupported neurons in suspension. The scaffold-encapsulated neurons integrated well within the injection site, extending neurites several hundred microns long into the host brain tissue. Overall, these results suggest that this biomaterial platform can be used to successfully improve the outcome of cell transplantation and neuro-regenerative therapies.
虽然细胞移植是治疗神经退行性疾病或中枢神经系统损伤功能缺陷的一种潜在策略，但移植细胞的低存活率是有效治疗的主要障碍。在本研究中，我们研究了由自组装肽RADA16-I组成的基于肽的纳米纤维支架在支持人类神经元重编程和成熟以及移植这些神经元方面的作用。诱导人类神经元是通过诱导多能干细胞（iPSC）的单一转录因子转导产生的，iPSC是再生疗法中一种很有前景的细胞来源。通过活细胞钙成像测定，与二维对照相比，封装在RADA16-I支架内的这些神经元显示出强劲的神经突生长，并表现出高水平的功能活性。当作为神经元贴壁功能网络的移植载体进行评估时，与悬浮状态下无支持的神经元传统移植相比，单分散RADA16-I微球显著提高了存活率（超过100倍）。支架封装的神经元在注射部位整合良好，神经突延伸到宿主脑组织中长达数百微米。总体而言，这些结果表明，这个生物材料平台可用于成功改善细胞移植和神经再生疗法的效果。
