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首页> 外文期刊>The European Journal of Neuroscience >Encapsulation of young donor age dopaminergic grafts in a GDNF GDNF ‐loaded collagen hydrogel further increases their survival, reinnervation, and functional efficacy after intrastriatal transplantation in hemi‐Parkinsonian rats
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Encapsulation of young donor age dopaminergic grafts in a GDNF GDNF ‐loaded collagen hydrogel further increases their survival, reinnervation, and functional efficacy after intrastriatal transplantation in hemi‐Parkinsonian rats

机译:在Hemi-Parkinsonian大鼠中,GDNF GDNF -Loaded胶原水凝胶中的年轻供体年龄的多巴胺能移植物进一步增加了它们的存活率,重新生存和功能性疗效。

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Abstract Biomaterials have been shown to significantly improve the outcome of cellular reparative approaches for Parkinson's disease in experimental studies because of their ability to provide transplanted cells with a supportive microenvironment and shielding from the host immune system. However, given that the margin for improvement in such reparative therapies is considerable, further studies are required to fully investigate and harness the potential of biomaterials in this context. Given that several recent studies have demonstrated improved brain repair in Parkinsonian models when using dopaminergic grafts derived from younger foetal donors, we hypothesized that encapsulating these cells in a supportive biomaterial would further improve their reparative efficacy. Thus, this study aimed to determine the impact of a GDNF ‐loaded collagen hydrogel on the survival, reinnervation, and functional efficacy of dopaminergic neurons derived from young donors. To do so, hemi‐Parkinsonian (6‐hydroxydopamine‐lesioned) rats received intrastriatal transplants of embryonic day 12 cells extracted from the rat ventral mesencephalon either alone, in a collagen hydrogel, with GDNF , or in a GDNF ‐loaded collagen hydrogel. Methamphetamine‐induced rotational behaviour was assessed at three weekly intervals for a total of 12?weeks, after which rats were sacrificed for postmortem assessment of graft survival. We found that, following intrastriatal transplantation to the lesioned striatum, the GDNF ‐loaded collagen hydrogel significantly increased the survival (4‐fold), reinnervation (5.4‐fold), and functional efficacy of the embryonic day 12 dopaminergic neurons. In conclusion, this study further demonstrates the significant potential of biomaterial hydrogel scaffolds for cellular brain repair approaches in neurodegenerative diseases such as Parkinson's disease.
机译:摘要已经显示出在实验研究中显着提高了帕金森病的细胞重复方法的结果,因为它们能够提供具有支持性微环境和宿主免疫系统屏蔽的移植细胞。然而,鉴于这种重复疗法改善的边距是相当大的,需要进一步的研究来完全研究和利用这种背景下生物材料的潜力。鉴于最近的几项研究表明,当使用从小胎儿供体的多巴胺能移植物时,帕金森尼模型的改善脑修复,我们假设封装这些细胞在支撑性生物材料中将进一步提高它们的重复效果。因此,本研究旨在确定GDNF -Loaded胶原水凝胶对来自年轻供体的多巴胺能神经元的存活率,再生和功能效果的影响。为此,Hemi-Parkinsonian(6-羟基二胺 - 损伤)大鼠接受了单独从大鼠水凝胶中的胚胎水凝胶中提取的胚胎第12次细胞的胃肠内移植,胶原水凝胶,具有GDNF,或在GDNF - 加载的胶原水凝胶中。甲基苯丙胺诱导的旋转行为以三个每周间隔进行评估,共12个时间,之后处死大鼠的移植物存活的后期评估。我们发现,随着损伤纹状体的脑内移植后,GDNF加载的胶原水凝胶显着增加了胚胎第12天多巴胺能神经元的存活率(4倍),重新生存(5.4倍)和功能性效果。总之,本研究进一步证明了生物材料水凝胶支架的显着潜力,用于帕金森病等神经变性疾病中的细胞脑修复方法。

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