RRC ID 50088
著者 Yokoi T, Tanaka T, Matsuzaka E, Tamalu F, Watanabe SI, Nishina S, Azuma N.
タイトル Effects of neuroactive agents on axonal growth and pathfinding of retinal ganglion cells generated from human stem cells.
ジャーナル Sci Rep
Abstract We recently established a novel method for generating functional human retinal ganglion cells (RGCs) from human induced pluripotent cells (hiPSCs). Here, we confirmed that RGCs can also be generated from human embryonic stem cells (hESCs). We investigated the usefulness of human RGCs with long axons for assessing the effects of chemical agents, such as the neurotrophic factor, nerve growth factor (NGF), and the chemorepellent factors, semaphorin 3 A (SEMA3A) and SLIT1. The effects of direct and local administration of each agent on axonal projection were evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and real-time imaging, in which the filopodia of the growth cone served as an excellent marker. A locally sustained agent system showed that the axons elongate towards NGF, but were repelled by SEMA3A and SLIT1. Focally transplanted beads that released SLIT1 bent the pathfinding of axons, imitating normal retinal development. Our innovative system for assessing the effects of chemical compounds using human RGCs may facilitate development of novel drugs for the examination, prophylaxis, and treatment of diseases. It may also be useful for observing the physiology of the optic nerve in vitro, which might lead to significant progress in the science of human RGCs.
巻・号 7(1)
ページ 16757
公開日 2017-12-1
DOI 10.1038/s41598-017-16727-1
PII 10.1038/s41598-017-16727-1
PMID 29196712
PMC PMC5711798
MeSH Axons / drug effects* Axons / metabolism* Cell Differentiation Cells, Cultured Drug Evaluation, Preclinical / methods Human Embryonic Stem Cells Humans Immunohistochemistry Induced Pluripotent Stem Cells Nerve Growth Factors / pharmacology* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Retinal Ganglion Cells / cytology Retinal Ganglion Cells / drug effects* Retinal Ganglion Cells / metabolism* Stem Cells / cytology Time-Lapse Imaging
IF 3.998
引用数 3
リソース情報
ヒト・動物細胞 KhES-1(HES0001) 409B2(HPS0076)