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与微囊化支持细胞短期共培养可加速体外培养新生猪胰岛细胞单层的功能成熟和分化。

Acceleration of functional maturation and differentiation of neonatal porcine islet cell monolayers shortly in vitro cocultured with microencapsulated sertoli cells.

机构信息

Section of Internal Medicine and Endocrine and Metabolic Sciences, Department of Internal Medicine, University of Perugia, 06126 Perugia, Italy.

出版信息

Stem Cells Int. 2010;2010:587213. doi: 10.4061/2010/587213. Epub 2009 Nov 19.

Abstract

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.

摘要

有限的尸体人类供体胰腺的可用性以及埃德蒙顿协议(Edmonton protocol)对人类胰岛同种异体移植的不完全成功,促使人们寻找新的胰岛素产生细胞来源,以替代胰岛素依赖型糖尿病(T1DM)的细胞治疗。从分离的新生猪胰岛(NPIs)开始,我们已经获得了细胞单层,这些细胞单层已经暴露于微囊化的单层 Sertoli 细胞(ESCs)中不同的时间段(7、14、21 天)。为了评估共培养的细胞单层的发育,我们研究了内分泌细胞表型分化标志物,或者 c-kit,造血干细胞标志物,最近涉及到人类和啮齿动物模型中β细胞亚群的生长和分化。发现 ESC 加速了 NPIs β细胞表型的成熟和分化,或者鉴定出一个对 c-kit 呈阳性标记的胰岛细胞亚群。胰岛素/c-kit 阳性细胞可能代表猪胰腺中一种新的、尚未被发现的功能不成熟的β细胞样成分。我们的 NPI 细胞单层的成熟和分化的加速可能为产生胰岛素产生细胞提供了一个潜在的新机会,这些细胞可能适合 T1DM 细胞治疗的实验试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9b/2956457/eeb6f3b1e551/SCI2010-587213.001.jpg

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