澳大利亚墨尔本大学Lachlan H. Thompson和Clare L. Parish研究组合作取得一项新成果。他们使用人多能干细胞同位重建中脑多巴胺 (mDA)通路的联合细胞和基因治疗方法。2022年2月17日出版的《细胞—干细胞》杂志发表了这项成果。
他们将 GDNF 病毒传递到纹状体，连同人类多能干细胞来源的 mDA 神经元的同位移植，概括了全脑 mDA 靶标神经支配。移植物提供了纹状体多巴胺水平的恢复和运动功能的校正以及与未被异位移植物很好地支配的额外mDA靶核的连接。这些结果表明，通过将适当的生长因子信号与特定细胞类型的移植相匹配，实现成人大脑中长距离回路的功能和解剖学精确重建的显著能力。
研究人员表示，帕金森病 (PD) 患者可以更换mDA神经元，以长期改善运动功能。成人大脑中长距离轴突生长的能力有限，这意味着细胞被异位移植到纹状体中。因此，一些 mDA 通路没有恢复，这可能是患者运动功能恢复不完全的基础。
附：英文原文
Title: A combined cell and gene therapy approach for homotopic reconstruction of midbrain dopamine pathways using human pluripotent stem cells
Author: Niamh Moriarty, Carlos W. Gantner, Cameron P.J. Hunt, Charlotte M. Ermine, Stefano Frausin, Serena Viventi, Dmitry A. Ovchinnikov, Deniz Kirik, Clare L. Parish, Lachlan H. Thompson
Issue&Volume: 2022-02-17
Abstract: Midbrain dopamine (mDA) neurons can be replaced in patients with Parkinson’s disease(PD) in order to provide long-term improvement in motor functions. The limited capacityfor long-distance axonal growth in the adult brain means that cells are transplantedectopically, into the striatal target. As a consequence, several mDA pathways arenot re-instated, which may underlie the incomplete restoration of motor function inpatients. Here, we show that viral delivery of GDNF to the striatum, in conjunctionwith homotopic transplantation of human pluripotent stem-cell-derived mDA neurons,recapitulates brain-wide mDA target innervation. The grafts provided re-instatementof striatal dopamine levels and correction of motor function and also connectivitywith additional mDA target nuclei not well innervated by ectopic grafts. These resultsdemonstrate the remarkable capacity for achieving functional and anatomically precisereconstruction of long-distance circuitry in the adult brain by matching appropriategrowth-factor signaling to grafting of specific cell types.
DOI: 10.1016/j.stem.2022.01.013
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00046-7
Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx
本期文章：《细胞—干细胞》：Online/在线发表
