Transplantation of Human Glial Progenitors to Immunodeficient Neonatal Mice with Amyotrophic Lateral Sclerosis (SOD1/rag2).
Transplantation of Human Glial Progenitors to Immunodeficient Neonatal Mice with Amyotrophic Lateral Sclerosis (SOD1/rag2).
复制标题
人神经胶质祖细胞移植给肌萎缩性侧索硬化症免疫缺陷新生小鼠（SOD1/rag2）。
DOI：
10.3390/antiox11061050
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发表时间：
2022-05-26
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
肌萎缩侧索硬化症（ALS）是一种进行性、致死性疾病，目前尚无有效的治疗方法。ALS的神经退行性特征是基于干细胞的再生方法的一个有吸引力的目标。不同类型的干细胞已经在临床前和临床环境中移植，但没有令人信服的结果。人胶质细胞限制性前体（hGRP）脑室内移植到新生儿，免疫缺陷小鼠挽救了髓鞘发育不良小鼠的寿命。脊髓内注射hGRP也在ALS小鼠模型中提供了益处。因此，我们最近开发了一种免疫缺陷型ALS模型（双突变SOD 1/rag 2），在这项研究中，我们测试了以前使用的策略，在髓鞘发育不良的小鼠脑室内移植hGRP免疫缺陷小鼠。为了最大限度地发挥潜在的治疗效果，将这些细胞植入新生儿体内。我们使用磁共振成像来研究神经变性的进展和治疗反应。一组动物用于生存评估。尸检分析包括免疫组织化学、尼氏染色和蛋白质印迹。细胞移植与改善动物存活率、减缓神经变性或错误折叠的超氧化物歧化酶1积累无关。尸检分析未发现任何存活的hGRP。移植到新生儿免疫缺陷受体并不能阻止ALS诱导的细胞丢失，这可能解释了缺乏积极的治疗效果。这项研究的结果与临床神经移植的适度效果一致。因此，我们敦促干细胞和ALS社区开发和实施细胞跟踪方法，以更好地了解临床中的细胞命运。
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no effective therapy. The neurodegenerative character of ALS was an appealing target for stem cell-based regenerative approaches. Different types of stem cells have been transplanted in both preclinical and clinical settings, but no convincing outcomes have been noted. Human glial restricted precursors (hGRPs) transplanted intraventricularly to neonatal, immunodeficient mice rescued lifespan of dysmyelinated mice. Intraspinal injection of hGRPs also provided benefits in the mouse model of ALS. Therefore, we have recently developed an immunodeficient model of ALS (double mutant SOD1/rag2), and, in this study, we tested the strategy previously used in dysmyelinated mice of intraventricular transplantation of hGRPs to immunodeficient mice. To maximize potential therapeutic benefits, the cells were implanted into neonates. We used magnetic resonance imaging to investigate the progression of neurodegeneration and therapeutic responses. A cohort of animals was devoted to survival assessment. Postmortem analysis included immunohistochemistry, Nissl staining, and Western blots. Cell transplantation was not associated with improved animal survival, slowing neurodegeneration, or accumulation of misfolded superoxide dismutase 1. Postmortem analysis did not reveal any surviving hGRPs. Grafting into neonatal immunodeficient recipients did not prevent ALS-induced cell loss, which might explain the lack of positive therapeutic effects. The results of this study are in line with the modest effects of clinical neurotransplantations. Therefore, we urge stem cell and ALS communities to develop and implement cell tracking methods to better understand cell fates in the clinic.
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影响因子：
5.3
作者：
Garbuzova-Davis S;Haller E;Navarro S;Besong TE;Boccio KJ;Hailu S;Khatib M;Sanberg PR;Appel SH;Borlongan CV
通讯作者：
Borlongan CV
影响因子：
5.1
作者：
Golubczyk, Dominika;Malysz-Cymborska, Izabela;Walczak, Piotr
通讯作者：
Walczak, Piotr
影响因子：
1.7
作者：
Komatsu, Kenichi;Imamura, Keiko;Inoue, Haruhisa
通讯作者：
Inoue, Haruhisa
影响因子：
4.6
作者：
Majchrzak, M.;Drela, K.;Stanaszek, L.
通讯作者：
Stanaszek, L.
影响因子：
2.7
作者：
Sandrock, Robert W.;Wheatley, Will;Campanelli, James T.
通讯作者：
Campanelli, James T.