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导管细胞重编程为产生胰岛素的β样细胞作为慢性胰腺炎潜在的β细胞替代来源

Ductal Cell Reprogramming to Insulin-Producing Beta-Like Cells as a Potential Beta Cell Replacement Source for Chronic Pancreatitis.

作者信息

Jawahar Aravinth P, Narayanan Siddharth, Loganathan Gopalakrishnan, Pradeep Jithu, Vitale Gary C, Jones Christopher M, Hughes Michael G, Williams Stuart K, Balamurugan Appakalai N

机构信息

Clinical Islet Cell Laboratory, Center for Cellular Transplantation, Cardiovascular Innovation Institute, Department of Surgery, University of Louisville, Louisville, KY 40202, United States.

Division of General Surgery, University of Louisville, Louisville, KY, 40202, United States.

出版信息

Curr Stem Cell Res Ther. 2019;14(1):65-74. doi: 10.2174/1574888X13666180918092729.

Abstract

Islet cell auto-transplantation is a novel strategy for maintaining blood glucose levels and improving the quality of life in patients with chronic pancreatitis (CP). Despite the many recent advances associated with this therapy, obtaining a good yield of islet infusate still remains a pressing challenge. Reprogramming technology, by making use of the pancreatic exocrine compartment, can open the possibility of generating novel insulin-producing cells. Several lineage-tracing studies present evidence that exocrine cells undergo dedifferentiation into a progenitor-like state from which they can be manipulated to form insulin-producing cells. This review will present an overview of recent reports that demonstrate the potential of utilizing pancreatic ductal cells (PDCs) for reprogramming into insulin- producing cells, focusing on the recent advances and the conflicting views. A large pool of ductal cells is released along with islets during the human islet isolation process, but these cells are separated from the pure islets during the purification process. By identifying and improving existing ductal cell culture methods and developing a better understanding of mechanisms by which these cells can be manipulated to form hormone-producing islet-like cells, PDCs could prove to be a strong clinical tool in providing an alternative beta cell source, thus helping CP patients maintain their long-term glucose levels.

摘要

胰岛细胞自体移植是一种维持慢性胰腺炎(CP)患者血糖水平和改善其生活质量的新策略。尽管这种疗法最近取得了许多进展,但获得高产率的胰岛输注液仍然是一个紧迫的挑战。重编程技术通过利用胰腺外分泌部分,可以开启生成新型胰岛素产生细胞的可能性。多项谱系追踪研究表明,外分泌细胞会去分化为祖细胞样状态,从中可以被操纵形成胰岛素产生细胞。本综述将概述近期的报告,这些报告展示了利用胰腺导管细胞(PDC)重编程为胰岛素产生细胞的潜力,重点关注近期的进展和存在争议的观点。在人类胰岛分离过程中,大量导管细胞与胰岛一起被释放出来,但在纯化过程中这些细胞与纯胰岛分离。通过识别和改进现有的导管细胞培养方法,并更好地理解如何操纵这些细胞形成产生激素的胰岛样细胞的机制,PDC可能成为一种强大的临床工具,提供替代的β细胞来源,从而帮助CP患者维持长期血糖水平。

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