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首页> 外文学位 >Three-dimensional culture of pancreatic precursor cells in poly(ethylene glycol)-based hydrogels: A tissue engineering approach to type 1 diabetes.
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Three-dimensional culture of pancreatic precursor cells in poly(ethylene glycol)-based hydrogels: A tissue engineering approach to type 1 diabetes.

机译：基于聚乙二醇的水凝胶中胰腺前体细胞的三维培养：一种针对1型糖尿病的组织工程方法。

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摘要

Islet cell transplantation restores insulin independence to patients with type 1 diabetes; however, access to this potentially curative therapy is limited by a severe shortage of transplantable cells. Renewable cell sources, including embryonic pancreatic precursors and embryonic stem cells, could provide an unlimited supply of transplantable islets if mechanisms can be elucidated to promote their selective in vitro differentiation into functioning beta cells. The primary objective of this thesis is to identify essential signaling cues to manipulate the behavior of embryonic pancreatic precursor cells encapsulated in three-dimensional PEG-based hydrogels toward the design of a tissue engineered scaffold to alleviate type 1 diabetes. PEG-based hydrogels are ideal candidates for the three-dimensional culture of pancreatic precursor cells due to their biocompatibility, resistance to protein and cell adhesion, and effective immunoisolation of encapsulated cells. Because they are bioinert, PEG hydrogels also provide a blank slate culture platform upon which the exposure and duration of individual signaling cues can be controlled. The ability to manipulate the encapsulating culture environment and provide specific and homogeneous signals to the entire cell population offers the opportunity to promote uniform cell differentiation. Within this context, this thesis first explores the differentiation of singly encapsulated pancreatic precursor cells in unmodified PEG hydrogels to determine this cell population's default pathway of differentiation in the absence of external signaling cues. Select soluble and insoluble cues were then added to the culture platform to enhance viability and direct differentiation of pancreatic precursor cells toward a functional, glucose-responsive beta cell fate. Human embryonic stem cells previously differentiated into a pancreatic precursor-like population were then encapsulated in PEG-based hydrogels to determine if beta cell differentiation could be similarly promoted in this clinically relevant cell population. Finally, PEG hydrogels were modified to promote scaffold vascularization, and thus provide a potential mechanism for efficient oxygen and nutrient diffusion to differentiated beta cells if cell-loaded hydrogel discs were implanted in vivo. This research provides a foundation for the tissue engineering of a transplantable beta cell population using PEG-based hydrogels and renewable cell sources.
机译：胰岛细胞移植可恢复1型糖尿病患者的胰岛素独立性。然而，由于严重缺乏可移植细胞，限制了这种潜在治疗方法的使用。如果可以阐明促进其选择性体外分化为功能性β细胞的机制，则包括胚胎胰腺前体和胚胎干细胞在内的可再生细胞来源可以提供无限量的可移植胰岛。本论文的主要目的是确定必要的信号提示，以操纵包裹在基于PEG的三维水凝胶中的胚胎胰腺前体细胞的行为，以设计组织工程支架以减轻1型糖尿病。基于PEG的水凝胶具有生物相容性，对蛋白质和细胞黏附的抗性以及封装细胞的有效免疫分离作用，因此是胰腺前体细胞三维培养的理想候选物。由于它们是生物惰性的，因此PEG水凝胶还提供了一个空白的平板培养平台，在该平台上可以控制各个信号提示的暴露时间和持续时间。操纵封装培养环境并向整个细胞群体提供特异性和均一信号的能力提供了促进均匀细胞分化的机会。在此背景下，本论文首先探讨了在未修饰的PEG水凝胶中单囊化的胰腺前体细胞的分化，以确定在没有外部信号提示的情况下该细胞群体的默认分化途径。然后将选择的可溶和不可溶的线索添加到培养平台，以增强生存力并指导胰腺前体细胞向功能性，葡萄糖反应性β细胞命运的方向分化。然后将先前分化成胰腺前体样群体的人类胚胎干细胞封装在基于PEG的水凝胶中，以确定在该临床相关细胞群体中是否可以类似地促进β细胞分化。最后，对PEG水凝胶进行修饰以促进支架的血管形成，从而为体内植入的载有水凝胶的椎间盘提供有效的氧气和营养物质向分化的β细胞扩散的潜在机制。该研究为使用基于PEG的水凝胶和可再生细胞来源的可移植β细胞群体的组织工程化提供了基础。

著录项

  • 作者

    Mason, Mariah Nicole.;

  • 作者单位

    University of Colorado at Boulder.;

  • 授予单位 University of Colorado at Boulder.;
  • 学科 Engineering Chemical.;Health Sciences Medicine and Surgery.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 276 p.
  • 总页数 276
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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