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一种用于增强人骨髓间充质干细胞管状组织生成的双室旋转生物反应器:用于血管组织再生的有前途的工具。

A double chamber rotating bioreactor for enhanced tubular tissue generation from human mesenchymal stem cells: a promising tool for vascular tissue regeneration.

机构信息

Giulio Natta Department of Chemistry, Materials, and Chemical Engineering, Politecnico di Milano, Milan, 20133, Italy.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, 4072, Australia.

出版信息

J Tissue Eng Regen Med. 2018 Jan;12(1):e42-e52. doi: 10.1002/term.2341. Epub 2017 Apr 5.

Abstract

Cardiovascular diseases represent a major global health burden, with high rates of mortality and morbidity. Autologous grafts are commonly used to replace damaged or failing blood vessels; however, such approaches are hampered by the scarcity of suitable graft tissue, donor site morbidity and poor long-term stability. Tissue engineering has been investigated as a means by which exogenous vessel grafts can be produced, with varying levels of success to date, a result of mismatched mechanical properties of these vessel substitutes and inadequate ex vivo vessel tissue genesis. In this work, we describe the development of a novel multifunctional dual-phase (air/aqueous) bioreactor, designed to both rotate and perfuse small-diameter tubular scaffolds and encourage enhanced tissue genesis throughout such scaffolds. Within this novel dynamic culture system, an elastomeric nanofibrous, microporous composite tubular scaffold, composed of poly(caprolactone) and acrylated poly(lactide-co-trimethylene-carbonate) and with mechanical properties approaching those of native vessels, was seeded with human mesenchymal stem cells (hMSCs) and cultured for up to 14 days in inductive (smooth muscle) media. This scaffold/bioreactor combination provided a dynamic culture environment that enhanced (compared with static controls) scaffold colonization, cell growth, extracellular matrix deposition and in situ differentiation of the hMSCs into mature smooth muscle cells, representing a concrete step towards our goal of creating a mature ex vivo vascular tissue for implantation. Copyright © 2016 John Wiley & Sons, Ltd.

摘要

心血管疾病是全球主要的健康负担之一,其死亡率和发病率都很高。自体移植物常用于替代受损或衰竭的血管;然而,这种方法受到合适移植物组织的稀缺、供体部位发病率和长期稳定性差的限制。组织工程已被研究作为一种可以产生外源性血管移植物的方法,但迄今为止,由于这些血管替代品的机械性能不匹配和体外血管组织生成不足,其成功率各不相同。在这项工作中,我们描述了一种新型多功能双相(空气/水相)生物反应器的开发,该生物反应器旨在旋转和灌注小直径管状支架,并促进整个支架的组织生成。在这个新颖的动态培养系统中,一种弹性纳米纤维、微孔复合管状支架,由聚己内酯和丙烯酰化聚(乳酸-共-三亚甲基碳酸酯)组成,其机械性能接近天然血管,用人类间充质干细胞(hMSCs)接种,并在诱导(平滑肌)培养基中培养长达 14 天。这种支架/生物反应器组合提供了一个动态的培养环境,增强了(与静态对照相比)支架的定植、细胞生长、细胞外基质的沉积和 hMSCs 在原位分化为成熟的平滑肌细胞,这是朝着我们创建用于植入的成熟体外血管组织的目标迈出的具体一步。版权所有 © 2016 约翰威立父子公司

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