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[通过胰岛再生实现再生医学:糖尿病的当前及未来疗法]

[Regenerative medicine by regenerating islets: present and future therapies for diabetes].

作者信息

Iwanaga Yasuhiro, Kanamune Jun, Kawaguchi Michiya, Takaori Kyoichi, Uemoto Shinji

机构信息

Department of Hepatobiliary, Pancreas and Transplant Surgery, Kyoto University, Kyoto, Japan.

出版信息

Nihon Geka Gakkai Zasshi. 2012 Sep;113(5):451-5.

Abstract

Beta cell replacement by islet transplantation is a promising clinical therapy for patients with type 1 diabetes because it satisfies safety issues and offers reliability in controlling blood glucose levels. One remaining problem is that it requires islets from two to three donor pancreases to achieve insulin independence, thus aggravating the donor shortage. Islet regeneration in vivo and generation of beta cells ex vivo followed by transplantation represent attractive therapeutic methods to restore the beta cell mass. Recent studies have suggested a number of postnatal pancreatic epithelial cells as candidate sources for future beta cell replacement therapy. Beta cells can reenter the cell cycle after a brief quiescent stage, suggesting the potential for engineering for expansion. The mechanisms of alpha cell-to-beta cell transdifferentiation can also be utilized to increase the beta cell population. Pancreatic ductal cells can proliferate and differentiate into regenerated beta cells. Pancreatic acinar cells are also observed to transdifferentiate into endocrinal cells, although infrequently under in vivo conditions. After a few more series of careful studies performed on human cells, the ultimate goal of translation to the clinic appears to be just around the corner. Islet cell transplantation will become a welcome new form of cell-regeneration therapy.

摘要

胰岛移植替代β细胞对1型糖尿病患者来说是一种很有前景的临床治疗方法,因为它解决了安全性问题,并且在控制血糖水平方面具有可靠性。仍然存在的一个问题是,需要两到三个供体胰腺的胰岛才能实现胰岛素自主分泌,这加剧了供体短缺的问题。体内胰岛再生以及体外生成β细胞然后进行移植是恢复β细胞数量的有吸引力的治疗方法。最近的研究表明,许多出生后的胰腺上皮细胞可作为未来β细胞替代疗法的候选来源。β细胞在短暂的静止期后可重新进入细胞周期,这表明具有通过工程技术进行扩增的潜力。α细胞向β细胞转分化的机制也可用于增加β细胞数量。胰腺导管细胞能够增殖并分化为再生的β细胞。胰腺腺泡细胞也被观察到可转分化为内分泌细胞,尽管在体内条件下这种情况很少见。在对人类细胞进行更多系列的仔细研究之后,转化到临床的最终目标似乎已近在咫尺。胰岛细胞移植将成为一种受欢迎的新型细胞再生疗法。

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