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Acceleration of Functional Maturation and Differentiation of Neonatal Porcine Islet Cell Monolayers Shortly In Vitro Cocultured with Microencapsulated Sertoli Cells

机译:与微囊化支持细胞短期共培养的新生猪胰岛细胞单层功能成熟和分化的加速。

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摘要

The limited availability of cadaveric human donor pancreata as well as the incomplete success of the Edmonton protocol for human islet allografts fasten search for new sources of insulin the producing cells for substitution cell therapy of insulin-dependent diabetes mellitus (T1DM). Starting from isolated neonatal porcine pancreatic islets (NPIs), we have obtained cell monolayers that were exposed to microencapsulated monolayered Sertoli cells (ESCs) for different time periods (7, 14, 21 days). To assess the development of the cocultured cell monolayers, we have studied either endocrine cell phenotype differentiation markers or c-kit, a hematopoietic stem cell marker, has recently been involved with growth and differentiation of β-cell subpopulations in human as well as rodent animal models. ESC which were found to either accelerate maturation and differentiation of the NPIs β-cell phenotype or identify an islet cell subpopulation that was marked positively for c-kit. The insulin/c-kit positive cells might represent a new, still unknown functionally immature β-cell like element in the porcine pancreas. Acceleration of maturation and differentiation of our NPI cell monolayers might generate a potential new opportunity to develop insulin-producing cells that may suite experimental trials for cell therapy of T1DM.
机译:尸体人类供体胰腺的可用性有限,以及埃德蒙顿协议对人类胰岛移植的不完全成功,加快了对胰岛素新来源的寻找,从而为胰岛素依赖型糖尿病(T1DM)的替代细胞治疗生产细胞。从分离的新生猪胰岛(NPI)开始,我们获得了在不同时间段(7、14、21天)暴露于微囊化单层Sertoli细胞(ESC)的细胞单层。为了评估共培养细胞单层的发育,我们研究了内分泌细胞表型分化标记物或造血干细胞标记物c-kit,最近已参与人类和啮齿动物中β细胞亚群的生长和分化楷模。被发现可以促进NPIsβ细胞表型的成熟和分化的ESC,或者可以识别出对c-kit阳性的胰岛细胞亚群。胰岛素/ c-kit阳性细胞可能代表了猪胰腺中新的,功能未知的功能不成熟的β细胞样元件。我们NPI细胞单层的成熟和分化的加速可能为开发产生胰岛素的细胞提供潜在的新机会,该细胞可能适合T1DM的细胞治疗实验。

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