Regenerating pancreatic beta-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis.
Regenerating pancreatic beta-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis.
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DOI：
10.1097/mot.0b013e3283344932
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发表时间：
2010-02
影响因子：
2.2
通讯作者：
Sharma A
中科院分区：
文献类型：
--
作者：
Juhl K;Bonner-Weir S;Sharma A
糖尿病是由胰腺 β 细胞功能不足引起的，因此补充新的葡萄糖反应性 β 细胞是一种重要的治疗选择。除了复制预先存在的 β 细胞外，还可以使用体外或体内方法从分化的成体细胞中产生新的 β 细胞。本综述将总结体内非 β 细胞细胞生成 β 细胞（新生）的最新进展，并讨论克服该过程当前局限性的方法。多个研究小组表明，成人胰管、腺泡甚至内分泌细胞都表现出细胞可塑性，并且可以在体内分化为β细胞。几种不同的方法，包括转录因子的错误表达和组织损伤，诱导体内胰岛素表达细胞的新生并改善糖尿病。最近的突破表明成体胰腺细胞形成新β细胞的细胞可塑性是开发基于体内再生的糖尿病疗法的积极的第一步。目前，新生过程效率低下，并且不能产生使高血糖正常化所需的足够数量的β细胞。然而，更好地了解调节成体胰腺细胞β细胞新生及其成熟为功能性葡萄糖反应性β细胞的机制可以使基于体内再生的治疗成为现实。
Diabetes results from inadequate functional mass of pancreatic β-cells, and so replenishing with new glucose-responsive β-cells is an important therapeutic option. In addition to replication of pre-existing β-cells, new β-cells can be produced from differentiated adult cells using in vitro or in vivo approaches. This review will summarize recent advances in in vivo generation of β-cells from cells that are not β-cells (neogenesis) and discuss ways to overcome current limitations of this process. Multiple groups have shown that adult pancreatic ducts, acinar and even endocrine cells exhibit cellular plasticity and can differentiate into β-cells in vivo. Several different approaches, including misexpression of transcription factors and tissue injury, induced neogenesis of insulin-expressing cells in vivo and ameliorated diabetes. Recent breakthroughs demonstrating cellular plasticity of adult pancreatic cells to form new β-cells are a positive first step towards developing in vivo regeneration based therapy for diabetes. Currently, neogenesis processes are inefficient and do not generate sufficient amounts of β-cells required to normalize hyperglycemia. However, improved understanding of mechanisms regulating neogenesis of β-cells from adult pancreatic cells and of their maturation into functional glucose-responsive β-cells can make therapies based on in vivo regeneration a reality.