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用于神经退行性疾病治疗的前瞻性研究:小鼠、犬原代培养悬浮细胞和人 QSV40 永生化细胞系胶质限制性祖细胞的免疫学特征和特性。

Immunological Characteristics and Properties of Glial Restricted Progenitors of Mice, Canine Primary Culture Suspensions, and Human QSV40 Immortalized Cell Lines for Prospective Therapies of Neurodegenerative Disorders.

机构信息

Institute of Human Genetics Polish Academy of Sciences, Poznan, Poland.

Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.

出版信息

Cell Transplant. 2019 Sep-Oct;28(9-10):1140-1154. doi: 10.1177/0963689719848355. Epub 2019 May 24.

Abstract

Neurodegeneration can be defined as a process in which neuronal structures and functions undergo changes leading to reduced neuronal survival and increased cell death in the central nervous system (CNS). Neuronal degeneration in specific regions of the CNS is a hallmark of many neurodegenerative disorders, and there is reliable proof that neural stem cells bring therapeutic benefits in treatment of neurological lesions. However, effective therapy with neural stem cells is associated with their biological properties. The assessment of immunological properties and comprehensive studies on the biology of glial restricted progenitors (GRP) are necessary prior to the application of these cells in humans. This study provides an in vitro characterization of the QSV40 glial human cell line, as well as murine and canine primary culture suspensions of GRPs and their mature, astrocytic forms using flow cytometry and immunohistochemical staining. Cytokines and chemokines released by GRPs were assessed by Multiplex ELISA. Some immunological differences observed among species suggest the necessity of reconsidering the pre-clinical model, and that careful testing of immunomodulatory strategies is required before cell transplantation into the CNS can be undertaken.

摘要

神经退行性变可以定义为中枢神经系统(CNS)中神经元结构和功能发生变化,导致神经元存活减少和细胞死亡增加的过程。CNS 特定区域的神经元变性是许多神经退行性疾病的标志,有可靠的证据表明神经干细胞在治疗神经损伤方面具有治疗益处。然而,神经干细胞的有效治疗与其生物学特性有关。在将这些细胞应用于人类之前,需要评估免疫特性并对神经胶质限制祖细胞(GRP)的生物学进行全面研究。本研究通过流式细胞术和免疫组织化学染色,对 QSV40 胶质人细胞系以及鼠和犬的 GRP 原代培养物及其成熟的星形胶质细胞形式进行了体外表征。通过多重 ELISA 评估了 GRP 释放的细胞因子和趋化因子。观察到物种之间存在一些免疫差异,这表明有必要重新考虑临床前模型,并且在将细胞移植到 CNS 之前,需要仔细测试免疫调节策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08b9/6767900/f7eb9c673f4b/10.1177_0963689719848355-fig1.jpg

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