Generation of beta cells from human pluripotent stem cells: Potential for regenerative medicine.
Generation of beta cells from human pluripotent stem cells: Potential for regenerative medicine.
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DOI：
10.1016/j.semcdb.2012.06.010
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发表时间：
2012-08
影响因子：
7.3
通讯作者：
Keller, Gordon
中科院分区：
文献类型：
--
作者：
Nostro, Maria Cristina;Keller, Gordon
I 型糖尿病中β细胞的丧失最终会导致胰岛素依赖和难以通过胰岛素注射来控制的严重并发症。鉴于与长期使用胰岛素相关的并发症，目前正在考虑将细胞替代疗法作为一种替代疗法，有一天可能会治愈这种疾病。过去10年，胰岛移植试验已经证明，可以补充I型糖尿病患者的β细胞功能，并至少暂时消除他们对胰岛素的依赖。虽然尚未达到最佳效果，但这些试验的成功已经证明了细胞替代疗法是治疗糖尿病的可行选择。由于供体胰岛的获取途径有限，人们开始寻找用于细胞治疗目的的β细胞的替代来源，并将许多研究人员的努力集中在从人类胚胎干细胞和诱导多能干细胞中提取此类细胞的挑战上。在过去的五年里，人们在了解控制 hPSC 谱系发育的信号通路方面取得了重大进展，因此，现在可以从 hESC 和 hiPSC 常规产生人胰岛素产生细胞。虽然这些成就令人印象深刻，但仍然存在重大挑战，因为在这些条件下产生的大多数胰岛素产生细胞都是多激素且无功能的，这可能反映了已知在胰腺发育阶段（称为“第一次转变”）的早期胚胎中出现的多激素群体的出现。在胰腺发育的第二阶段或过渡期间出现的功能性β细胞是由hPSC产生的，但只有在将祖细胞阶段细胞移植到免疫功能低下的小鼠体内后才能检测到它们。取得这一成功后，我们现在面临的挑战是确定控制 hPSC 的第二个过渡群体发育和成熟的途径，并为体外生成功能性 β 细胞建立条件。
The loss of beta cells in Type I Diabetes ultimately leads to insulin dependence and major complications that are difficult to manage by insulin injections. Given the complications associated with long-term administration of insulin, cell-replacement therapy is now under consideration as an alternative treatment that may someday provide a cure for this disease. Over the past 10 years, islet transplantation trials have demonstrated that it is possible to replenish beta cell function in Type I Diabetes patients and, at least temporarily, eliminate their dependency on insulin. While not yet optimal, the success of these trials has provided proof-of-principle that cell replacement therapy is a viable option for treating diabetes. Limited access to donor islets has launched a search for alternative source of beta cells for cell therapy purposes and focused the efforts of many investigators on the challenge of deriving such cells from human embryonic and induced pluripotent stem cells. Over the past five years, significant advances have been made in understanding the signaling pathways that control lineage development from hPSCs and as a consequence, it is now possible to routinely generate human insulin producing cells from both hESCs and hiPSCs. While these achievements are impressive, significant challenges do still exist, as the majority of insulin producing cells generated under these conditions are polyhormonal and non functional, likely reflecting the emergence of the polyhormonal population that is known to arise in the early embryo during the phase of pancreatic development known as the ‘first transition’. Functional beta cells, which arise during the second phase or transition of pancreatic development have been generated from hPSCs, however they are detected only following transplantation of progenitor stage cells into immunocompromised mice. With this success, our challenge now is to define the pathways that control the development and maturation of this second transition population from hPSCs, and establish conditions for the generation of functional beta cells in vitro.
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