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タイトル: | Pretreatment with Perlecan-Conjugated Laminin-E8 Fragment Enhances Maturation of Grafted Dopaminergic Progenitors in Parkinson’s Disease Model |
著者: | Adachi, Hiromasa Morizane, Asuka Torikoshi, Sadaharu Raudzus, Fabian Taniguchi, Yukimasa Miyamoto, Susumu Sekiguchi, Kiyotoshi Takahashi, Jun |
著者名の別形: | 足立, 拓優 森實, 飛鳥 取越, 貞治 髙橋, 淳 |
キーワード: | Parkinson's disease dopaminergic neurons cell transplantation laminin perlecan |
発行日: | Jul-2022 |
出版者: | Oxford University Press (OUP) |
誌名: | Stem Cells Translational Medicine |
巻: | 11 |
号: | 7 |
開始ページ: | 767 |
終了ページ: | 777 |
抄録: | The therapeutic effect of a cell replacement therapy for Parkinson's disease (PD) depends on the proper maturation of grafted dopaminergic (DA) neurons and their functional innervation in the host brain. In the brain, laminin, an extracellular matrix protein, regulates signaling pathways for the survival and development of neurons by interacting with integrins. The heparan sulfate (HS) chain binds mildly to various neurotrophic factors and regulates their intracellular signaling. Perlecan-conjugated laminin 511/521-E8 fragments (p511/p521) were designed to contain an integrin-binding site and HS chains. Here we examined the effect of treating DA progenitors with p511/p521 prior to transplantation in rodent PD models. In vitro and in vivo experiments showed that p511/p521 treatment enhanced the maturation and neurite extension of the grafted DA progenitors by activating RAS-ERK1/2 signaling. This strategy will contribute to an efficient cell replacement therapy for PD in the future. |
著作権等: | © The Author(s) 2022. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/282094 |
DOI(出版社版): | 10.1093/stcltm/szac033 |
PubMed ID: | 35605097 |
出現コレクション: | 学術雑誌掲載論文等 |
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