Ex vivo Expansion of Human Adult Pancreatic Cells with Properties of Distributed Stem Cells by Suppression of Asymmetric Cell Kinetics.
Ex vivo Expansion of Human Adult Pancreatic Cells with Properties of Distributed Stem Cells by Suppression of Asymmetric Cell Kinetics.
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DOI：
10.4172/2157-7633.1000149
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Sherley J
中科院分区：
文献类型：
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作者：
Paré J;Sherley J
如果胰腺干细胞可用于研究，I型糖尿病（T1D）的移植治疗可能会得到改善。与肉眼可见的胰岛不同，胰腺组织干细胞可以更容易地进入腹膜后胰腺环境，从而可能实现更有效的胰腺再生。不幸的是，成人胰腺是否真的含有更新干细胞仍然是糖尿病研究中的一个有争议的问题。我们评估了我们实验室开发的一种新方法，用于从成人组织中扩增更新的分布式干细胞（DSC），作为为成人胰腺干细胞提供更多证据的一种手段，并可能提高其在未来临床研究中的可用性。新方法旨在将DSC从不对称自我更新转换为对称自我更新，这促进了它们在培养中的指数扩增，同时减少了分化细胞的产生。这种方法被称为抑制不对称细胞动力学（SACK），它使用天然嘌呤代谢物来完成自我更新模式的转变。评价SACK嘌呤代谢物黄嘌呤、黄嘌呤核苷和次黄嘌呤促进成人死后供体胰腺DSCs扩增的作用。黄嘌呤和黄嘌呤核苷对于衍生具有指示人胰腺DSC的特性的细胞的合并和克隆群体都是有效的。扩增的人细胞株具有标志性SACK试剂可抑制的不对称细胞动力学，产生α细胞和β细胞的Ngn 3+双能前体，并且在免疫缺陷小鼠中无致瘤性。我们的研究结果支持成人胰腺中存在胰腺DSCs，并指出了增加其未来临床评估可用性的潜在途径。
Transplantation therapy for type I diabetes (T1D) might be improved if pancreatic stem cells were readily available for investigation. Unlike macroscopic islets, pancreatic tissue stem cells could more easily access the retroperitoneal pancreatic environment and thereby might achieve more effective pancreatic regeneration. Unfortunately, whether the adult pancreas actually contains renewing stem cells continues as a controversial issue in diabetes research. We evaluated a new method developed in our lab for expanding renewing distributed stem cells (DSCs) from adult tissues as a means to provide more evidence for adult pancreatic stem cells, and potentially advance their availability for future clinical investigation. The new method was designed to switch DSCs from asymmetric self-renewal to symmetric self-renewal, which promotes their exponential expansion in culture with reduced production of differentiated cells. Called suppression of asymmetric cell kinetics (SACK), the method uses natural purine metabolites to accomplish the self-renewal pattern shift. The SACK purine metabolites xanthine, xanthosine, and hypoxanthine were evaluated for promoting expansion of DSCs from the pancreas of adult human postmortem donors. Xanthine and xanthosine were effective for deriving both pooled and clonal populations of cells with properties indicative of human pancreatic DSCs. The expanded human cell strains had signature SACK agent-suppressible asymmetric cell kinetics, produced Ngn3+ bipotent precursors for α-cells and β-cells, and were non-tumorigenic in immunodeficient mice. Our findings support the existence of pancreatic DSCs in the adult human pancreas and indicate a potential path to increasing their availability for future clinical evaluation.