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首页> 外文学位 >Investigation of mesenchymal stem cells and the development of experimental strategies for rescuing glaucomatous eyes using a stem cell-based therapy.
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Investigation of mesenchymal stem cells and the development of experimental strategies for rescuing glaucomatous eyes using a stem cell-based therapy.

机译：间充质干细胞的研究以及使用基于干细胞的疗法挽救青光眼的实验策略的发展。

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摘要

Glaucoma, the second leading cause of blindness in the world, is a hereditary ocular disease and about 60 million people suffer from it. However, currently there are no remedies to cure glaucoma. As a potential solution to rescue degenerating retinas, stem cells have been investigated extensively and the effects of morphological neuroprotection or functional recovery have been reported. In the present studies, I aimed to investigate two main topics of research. From the first topic, we demonstrated MSCs from Brown Norway rats are a self-renewing, multi-potent population. More importantly, we provide the first evidence that bone marrow MSCs are capable of promoting neurite outgrowth from adult hippocampal progenitor cells (AHPCs).;For the second topic of research, mouse MSCs were engineered to over-express brain-derived neurotrophic factor (BDNF) and/or glial cell-derived neurotrophic factor (GDNF) together with green fluorescent protein (GFP), as a strategy for stem cell-based therapy. Our results show MSCs, infected with lentiviral vectors encoding BDNF or GDNF, noticeably increased the release of bioactive neurotrophic factors in vitro..;For our in vivo study of stem cell-therapy, two different mouse models of experimental glaucoma were studied. MSCs, following intraocular transplantation, survived up to 4 months post-transplant (PT) in the host retina of adult DBA/2J mice. Interestingly, our results indicated MSCs expressing GDNF played a potential role in alleviating glial activation on host retinas. Importantly, our data show GDNF/BDNF-MSCs contributed to preservation of the inner retina of the recipient eye, compared to the control fellow eye.;An additional transgenic mouse model of glaucoma, Myocilin (MYOC)-mutant mice, was investigated. Our preliminary study showed transplanted MSCs survived up to 11.5 months-PT in the adult host retina. No significant changes in the number of retinal ganglion cells between experimental and control eyes were found at 11.5 months-PT.;These studies are the first to characterize bone marrow-derived MSCs from Brown Norway rats and to study potential neuroprotective effects of transplanted MSCs on the host retinas of DBA/2J and MYOC-mice. This study provides an experimental strategy towards clinical applications in terms of using MSCs as a potential autograft and long-term neuroprotection via neurotrophic factor delivery for retinodegenerative diseases.
机译：青光眼是世界上第二大致盲原因，是一种遗传性眼病，约有六千万人患有这种疾病。但是，目前尚无治疗青光眼的药物。作为挽救退化的视网膜的潜在解决方案，已经对干细胞进行了广泛的研究，并且已经报道了形态神经保护或功能恢复的作用。在本研究中，我旨在研究两个主要的研究主题。从第一个主题开始，我们证明了来自褐挪威鼠的MSC是一种自我更新的，多能的种群。更重要的是，我们提供了第一个证据，表明骨髓间充质干细胞能够促进成年海马祖细胞（AHPC）的神经突生长。第二个研究课题是，小鼠MSC被工程化为过表达脑源性神经营养因子（BDNF）。 ）和/或神经胶质细胞源性神经营养因子（GDNF）以及绿色荧光蛋白（GFP）作为基于干细胞的治疗策略。我们的结果表明，感染了编码BDNF或GDNF的慢病毒载体的MSCs体外显着增加了生物活性神经营养因子的释放。.；对于干细胞疗法的体内研究，研究了两种不同的实验性青光眼小鼠模型。眼内移植后，MSC在成年DBA / 2J小鼠的宿主视网膜中存活长达4个月（PT）。有趣的是，我们的结果表明表达GDNF的MSC在减轻宿主视网膜胶质细胞活化中起着潜在的作用。重要的是，我们的数据显示，与对照组的同眼相比，GDNF / BDNF-MSCs有助于保护受体眼的视网膜。;研究了青光眼的另一种转基因小鼠模型，即Myocilin（MYOC）突变小鼠。我们的初步研究表明，成年宿主视网膜中移植的MSC存活时间最长可达11.5个月。 PT 11.5个月时，实验眼和对照眼之间的视网膜神经节细胞数量没有显着变化。这些研究是首次鉴定来自Brown Norway大鼠的骨髓间充质干细胞，并研究了移植的MSC对神经干细胞的潜在神经保护作用。 DBA / 2J和MYOC小鼠的宿主视网膜。这项研究为临床应用提供了一种实验策略，涉及使用MSCs作为潜在的自体移植物以及通过神经营养因子传递对视网膜再生疾病进行长期神经保护。

著录项

  • 作者

    Ye, Eun-Ah.;

  • 作者单位

    Iowa State University.;

  • 授予单位 Iowa State University.;
  • 学科 Biology Neuroscience.;Biology Cell.;Health Sciences Ophthalmology.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 186 p.
  • 总页数 186
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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