Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke

Abstract Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, major obstacles to clinical use still exist. To circumvent complications related to intracerebral administration, we implanted hum...

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Autores principales:	I-Hui Lee, Shiang-Suo Huang, Ching-Yu Chuang, Ko-Hsun Liao, Li-Hsin Chang, Chia-Chi Chuang, Yu-Shih Su, Hung-Jui Lin, Jui-Yu Hsieh, Shu-Han Su, Oscar Kuang-Sheng Lee, Hung-Chih Kuo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/237fb55871804c0987eccb30e40fc186
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spelling	oai:doaj.org-article:237fb55871804c0987eccb30e40fc1862021-12-02T16:06:48ZDelayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke10.1038/s41598-017-02137-w2045-2322https://doaj.org/article/237fb55871804c0987eccb30e40fc1862017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02137-whttps://doaj.org/toc/2045-2322Abstract Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, major obstacles to clinical use still exist. To circumvent complications related to intracerebral administration, we implanted human iPSC-NPCs epidurally over the peri-infarct cortex 7 days after permanent middle cerebral artery occlusion in adult rats. Compared to controls, cell-treated rats showed significant improvements in paretic forelimb usage and grip strength from 10 days post-transplantation (dpt) onwards, as well as reductions in lesion volumes, inflammatory infiltration and astrogliosis at 21 dpt. Few iPSC-NPCs migrated into rat peri-infarct cortices and exhibited poor survival in tissue. To examine the paracrine therapeutic mechanisms of epidural iPSC-NPC grafts, we used transmembrane co-cultures of human iPSC-NPCs with rat cortical cells subjected to oxygen-glucose deprivation. Compared to other human stem cells, iPSC-NPCs were superior at promoting neuronal survival and outgrowth, and mitigating astrogliosis. Using comparative whole-genome microarrays and cytokine neutralization, we identified a neurorestorative secretome from iPSC-NPCs, and neutralizing enriched cytokines abolished neuroprotective effects in co-cultures. This proof-of-concept study demonstrates a relatively safe, yet effective epidural route for delivering human iPSC-NPCs, which acts predominately through discrete paracrine effects to promote functional recovery after stroke.I-Hui LeeShiang-Suo HuangChing-Yu ChuangKo-Hsun LiaoLi-Hsin ChangChia-Chi ChuangYu-Shih SuHung-Jui LinJui-Yu HsiehShu-Han SuOscar Kuang-Sheng LeeHung-Chih KuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q I-Hui Lee Shiang-Suo Huang Ching-Yu Chuang Ko-Hsun Liao Li-Hsin Chang Chia-Chi Chuang Yu-Shih Su Hung-Jui Lin Jui-Yu Hsieh Shu-Han Su Oscar Kuang-Sheng Lee Hung-Chih Kuo Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke
description	Abstract Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, major obstacles to clinical use still exist. To circumvent complications related to intracerebral administration, we implanted human iPSC-NPCs epidurally over the peri-infarct cortex 7 days after permanent middle cerebral artery occlusion in adult rats. Compared to controls, cell-treated rats showed significant improvements in paretic forelimb usage and grip strength from 10 days post-transplantation (dpt) onwards, as well as reductions in lesion volumes, inflammatory infiltration and astrogliosis at 21 dpt. Few iPSC-NPCs migrated into rat peri-infarct cortices and exhibited poor survival in tissue. To examine the paracrine therapeutic mechanisms of epidural iPSC-NPC grafts, we used transmembrane co-cultures of human iPSC-NPCs with rat cortical cells subjected to oxygen-glucose deprivation. Compared to other human stem cells, iPSC-NPCs were superior at promoting neuronal survival and outgrowth, and mitigating astrogliosis. Using comparative whole-genome microarrays and cytokine neutralization, we identified a neurorestorative secretome from iPSC-NPCs, and neutralizing enriched cytokines abolished neuroprotective effects in co-cultures. This proof-of-concept study demonstrates a relatively safe, yet effective epidural route for delivering human iPSC-NPCs, which acts predominately through discrete paracrine effects to promote functional recovery after stroke.
format	article
author	I-Hui Lee Shiang-Suo Huang Ching-Yu Chuang Ko-Hsun Liao Li-Hsin Chang Chia-Chi Chuang Yu-Shih Su Hung-Jui Lin Jui-Yu Hsieh Shu-Han Su Oscar Kuang-Sheng Lee Hung-Chih Kuo
author_facet	I-Hui Lee Shiang-Suo Huang Ching-Yu Chuang Ko-Hsun Liao Li-Hsin Chang Chia-Chi Chuang Yu-Shih Su Hung-Jui Lin Jui-Yu Hsieh Shu-Han Su Oscar Kuang-Sheng Lee Hung-Chih Kuo
author_sort	I-Hui Lee
title	Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke
title_short	Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke
title_full	Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke
title_fullStr	Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke
title_full_unstemmed	Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke
title_sort	delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/237fb55871804c0987eccb30e40fc186
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Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke

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