Simple Modular Bioreactors for Tissue Engineering: A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation, and Prevascularization
Simple Modular Bioreactors for Tissue Engineering: A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation, and Prevascularization
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DOI：
10.1089/ten.tec.2010.0241
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发表时间：
2010-12-01
影响因子：
3
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Lovett, Michael;Rockwood, Danielle;Kaplan, David L.
大规模组织工程受到营养物灌注和质量运输限制，尤其是氧扩散的限制，这将构建体的发育限制为小于临床相关尺寸，并限制了体内整合的能力。这项工作的目标是开发一种组织工程的模块化方法，从一开始就考虑支架和组织尺寸、运输问题以及体内手术植入。人间充质干细胞 (hMSC) 被用作模型细胞类型，因为它们的分化已针对几种不同的细胞谱系进行了研究，但结果往往相互矛盾。展示了在不同氧张力下分化的 hMSC 表达谱的变化，证明了脂肪形成 (20% O-2) 和软骨形成 (5% O-2) 分化的组织特异性氧需求。通过开发生物反应器系统，使用多孔丝管灌注 hMSC 接种的胶原凝胶，增强了氧气和营养物质的输送，从而增强了凝胶内的氧气输送和细胞活力。这些系统使用简单且具有多功能性，可以系统地研究细胞含量、氧气和细胞功能之间的关系。这些数据可以与氧传输模型相结合，以导出最小尺寸的模块化单元，用于构建临床相关的组织工程结构，这是一种可用于血管化目标组织的通用策略。
Large-scale tissue engineering is limited by nutrient perfusion and mass transport limitations, especially oxygen diffusion, which restrict construct development to smaller than clinically relevant dimensions and limit the ability for in vivo integration. The goal of this work was to develop a modular approach to tissue engineering, where scaffold and tissue size, transport issues, and surgical implantation in vivo are considered from the outset. Human mesenchymal stem cells (hMSCs) were used as the model cell type, as their differentiation has been studied for several different cell lineages and often with conflicting results. Changes in the expression profiles of hMSCs differentiated under varied oxygen tensions are presented, demonstrating tissue-specific oxygen requirements for both adipogenic (20% O-2) and chondrogenic (5% O-2) differentiation. Oxygen and nutrient transport were enhanced by developing a bioreactor system for perfusing hMSC-seeded collagen gels using porous silk tubes, resulting in enhanced oxygen transport and cell viability within the gels. These systems are simple to use and scaled for versatility, to allow for the systematic study of relationships between cell content, oxygen, and cell function. The data may be combined with oxygen transport modeling to derive minimally sized modular units for construction of clinically relevant tissue-engineered constructs, a generic strategy that may be employed for vascularized target tissues.