Reprogramming of Pancreatic Acinar Cells to Functional Beta Cells by In Vivo Transduction of a Polycistronic Construct Containing Pdx1, Ngn3, MafA in Mice.
Reprogramming of Pancreatic Acinar Cells to Functional Beta Cells by In Vivo Transduction of a Polycistronic Construct Containing Pdx1, Ngn3, MafA in Mice.
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DOI：
10.1002/cpsc.21
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发表时间：
2017-02-02
影响因子：
--
通讯作者：
Zhou Q
中科院分区：
文献类型：
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作者：
Cavelti-Weder C;Zumsteg A;Li W;Zhou Q
出生后产生新的β细胞是再生医学的一个关键焦点，可以极大地帮助糖尿病的主要健康负担。已经使用四种不同的方法描述了β细胞再生：1）从成人胰腺的推定前体细胞发育β细胞，称为新生，2）复制现有的β细胞，3）从胚胎或诱导的多能干细胞分化，以及4）将非β细胞重编程为β细胞。我们实验室的研究表明，β细胞重编程可以通过用含有三种发育重要的转录因子Pdx 1、Ngn 3和MafA的病毒构建体转导成人胰腺组织来实现。该方案概述了含有三种转录因子的多顺反子构建体的产生、多顺反子病毒的扩增和纯化以及成年小鼠中腺泡至β细胞重编程的体内转导。最终目标是产生在表型上类似于内源性β细胞的β样细胞，并尽可能接近潜在的翻译应用。
To generate new beta-cells after birth is a key focus of regenerative medicine that could greatly aid the major health burden of diabetes. Beta-cell regeneration has been described using four different approaches: 1) the development of beta-cells from putative precursor cells of the adult pancreas termed neogenesis, 2) replication of existing beta-cells, 3) differentiation from embryonic or induced pluripotent stem cells, and 4) reprogramming of non-beta to beta-cells. Studies from our laboratory have shown that beta-cell reprogramming can be achieved by transduction of adult pancreatic tissues with viral constructs containing the three developmentally important transcription factors Pdx1, Ngn3, and MafA. This protocol outlines the generation of a polycistronic construct containing the three transcription factors, the expansion and purification of the polycistronic virus and in vivo transduction for acinar to beta-cell reprogramming in adult mice. The ultimate goal is to generate beta-like cells that resemble endogenous beta-cells in phenotype and function as closely as possible for potential translational applications.