Physiomimetic Fluidic Culture Platform on Microwell-Patterned Porous Collagen Scaffold for Human Pancreatic Islets.

IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING
Hiroyuki Kato, Huajian Chen, Kuang-Ming Shang, Kenji Izumi, Naoya Koba, Takanori Tsuchiya, Naoki Kawazoe, Janine Quijano, Keiko Omori, Chris Orr, Meirigeng Qi, Hsun Teresa Ku, Fouad Kandeel, Yu-Chong Tai, Guoping Chen, Hirotake Komatsu
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引用次数: 0

Abstract

Pancreatic islet transplantation is one of the clinical options for certain types of diabetes. However, difficulty in maintaining islets prior to transplantation limits the clinical expansion of islet transplantations. Our study introduces a dynamic culture platform developed specifically for primary human islets by mimicking the physiological microenvironment, including tissue fluidics and extracellular matrix support. We engineered the dynamic culture system by incorporating our distinctive microwell-patterned porous collagen scaffolds for loading isolated human islets, enabling vertical medium flow through the scaffolds. The dynamic culture system featured four 12 mm diameter islet culture chambers, each capable of accommodating 500 islet equivalents (IEQ) per chamber. This configuration calculates > five-fold higher seeding density than the conventional islet culture in flasks prior to the clinical transplantations (442 vs 86 IEQ/cm2). We tested our culture platform with three separate batches of human islets isolated from deceased donors for an extended period of 2 weeks, exceeding the limits of conventional culture methods for preserving islet quality. Static cultures served as controls. The computational simulation revealed that the dynamic culture reduced the islet volume exposed to the lethal hypoxia (< 10 mmHg) to ~1/3 of the static culture. Dynamic culture ameliorated the morphological islet degradation in long-term culture and maintained islet viability, with reduced expressions of hypoxia markers. Furthermore, dynamic culture maintained the islet metabolism and insulin-secreting function over static culture in a long-term culture. Collectively, the physiological microenvironment-mimetic culture platform supported the viability and quality of isolated human islets at high-seeding density. Such a platform has a high potential for broad applications in cell therapies and tissue engineering, including extended islet culture prior to clinical islet transplantations and extended culture of stem cell-derived islets for maturation.

微孔胶原支架上的人胰岛仿生流体培养平台
胰岛移植是治疗某些类型糖尿病的临床选择之一。然而,胰岛移植前的维护困难限制了胰岛移植的临床推广。我们的研究通过模拟生理微环境,包括组织流体学和细胞外基质支持,引入了专为原代人类胰岛开发的动态培养平台。我们设计的动态培养系统采用了独特的微孔图案多孔胶原支架,用于装载分离的人胰岛,使培养基垂直流过支架。动态培养系统有四个直径为 12 毫米的胰岛培养室,每个培养室可容纳 500 个胰岛当量(IEQ)。与临床移植前在烧瓶中进行的传统胰岛培养相比,这种配置计算出的播种密度要高出五倍(442 比 86 IEQ/cm2)。我们用三批从已故捐献者体内分离出来的人体胰岛对我们的培养平台进行了为期两周的测试,测试时间超过了传统培养方法在保存胰岛质量方面的极限。静态培养作为对照。计算模拟显示,动态培养将暴露于致命低氧(< 10 mmHg)的胰岛体积减少到静态培养的约 1/3。动态培养改善了长期培养中的胰岛形态退化,维持了胰岛的活力,同时减少了缺氧标记物的表达。此外,在长期培养中,动态培养比静态培养更能维持胰岛的新陈代谢和胰岛素分泌功能。总之,生理微环境模拟培养平台支持高密度分离人胰岛的活力和质量。这种平台在细胞疗法和组织工程方面具有广泛的应用潜力,包括临床胰岛移植前的胰岛延长培养和干细胞衍生胰岛成熟的延长培养。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Transplantation
Cell Transplantation 生物-细胞与组织工程
CiteScore
6.00
自引率
3.00%
发文量
97
审稿时长
6 months
期刊介绍: Cell Transplantation, The Regenerative Medicine Journal is an open access, peer reviewed journal that is published 12 times annually. Cell Transplantation is a multi-disciplinary forum for publication of articles on cell transplantation and its applications to human diseases. Articles focus on a myriad of topics including the physiological, medical, pre-clinical, tissue engineering, stem cell, and device-oriented aspects of the nervous, endocrine, cardiovascular, and endothelial systems, as well as genetically engineered cells. Cell Transplantation also reports on relevant technological advances, clinical studies, and regulatory considerations related to the implantation of cells into the body in order to provide complete coverage of the field.
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