Cell-assembled extracellular matrix (CAM) sheet production: Translation from using human to large animal cells.
Cell-assembled extracellular matrix (CAM) sheet production: Translation from using human to large animal cells.
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DOI：
10.1177/2041731420978327
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发表时间：
2021-01
影响因子：
8.2
通讯作者：
L'Heureux N
中科院分区：
文献类型：
--
作者：
Torres Y;Gluais M;Da Silva N;Rey S;Grémare A;Magnan L;Kawecki F;L'Heureux N
我们利用人类成纤维细胞在体外产生的细胞组装细胞外基质（CAM）片创建了完全生物组织工程血管移植物（TEVG）。大型动物 TEVG 将允许在临床相关环境（移植物大小和同种异体环境）中进行长期临床前研究。因此，比较了犬、猪、羊和人皮肤成纤维细胞形成 CAM 片的能力。血清来源以物种依赖性方式极大地影响了 CAM 生产。绵羊细胞产生最同质和最强的动物 CAM 片，但尽管血清、抗坏血酸、胰岛素或生长因子补充剂存在差异，但仍然比人类片薄弱约 3 倍。观察到人类和绵羊在细胞生长动力学、组织发育以及组织结构和组成方面的主要差异。这项研究证明了成纤维细胞行为的关键物种间差异，以及在需要长期培养的组织工程结构的开发过程中尝试用动物细胞替代人类细胞时它们如何构成挑战。
We have created entirely biological tissue-engineered vascular grafts (TEVGs) using sheets of cell-assembled extracellular matrix (CAM) produced by human fibroblasts in vitro. A large animal TEVG would allow long-term pre-clinical studies in a clinically relevant setting (graft size and allogeneic setting). Therefore, canine, porcine, ovine, and human skin fibroblasts were compared for their ability to form CAM sheets. Serum sourcing greatly influenced CAM production in a species-dependent manner. Ovine cells produced the most homogenous and strongest animal CAM sheets but remained ≈3-fold weaker than human sheets despite variations of serum, ascorbate, insulin, or growth factor supplementations. Key differences in cell growth dynamics, tissue development, and tissue architecture and composition were observed between human and ovine. This study demonstrates critical species-to-species differences in fibroblast behavior and how they pose a challenge when attempting to substitute animal cells for human cells during the development of tissue-engineered constructs that require long-term cultures.
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