基因漂移和实验室培养中的干细胞黏附是培养肉生产面临的问题吗?

Are genetic drift and stem cell adherence in laboratory culture issues for cultivated meat production?

作者信息

Jaime-Rodríguez Manuel, Cadena-Hernández Ana Laura, Rosales-Valencia Lorena Denisee, Padilla-Sánchez Juan Miguel, Chavez-Santoscoy Rocio Alejandra

机构信息

Tecnologico de Monterrey, School of Engineering and Sciences Monterrey, Monterrey, Mexico.

出版信息

Front Nutr. 2023 Aug 28;10:1189664. doi: 10.3389/fnut.2023.1189664. eCollection 2023.

Abstract

Mesenchymal stem cell-based cultivated meat is a promising solution to the ecological and ethical problems posed by traditional meat production, since it exhibits a protein content and composition that is more comparable to original meat proteins than any other source of cultivated meat products, including plants, bacteria, and fungi. Nonetheless, the nature and laboratory behavior of mesenchymal stem cells pose two significant challenges for large-scale production: genetic drift and adherent growth in culture. Culture conditions used in the laboratory expose the cells to a selective pressure that causes genetic drift, which may give rise to oncogene activation and the loss of "stemness." This is why genetic and functional analysis of the cells during culture is required to determine the maximum number of passages within the laboratory where no significant mutations or loss of function are detected. Moreover, the adherent growth of mesenchymal stem cells can be an obstacle for their large-scale production since volume to surface ratio is limited for high volume containers. Multi-tray systems, roller bottles, and microcarriers have been proposed as potential solutions to scale-up the production of adherent cells required for cultivated meat. The most promising solutions for the safety problems and large-scale obstacles for cultivated meat production are the determination of a limit number of passages based on a genetic analysis and the use of microcarriers from edible materials to maximize the volume to surface proportion and decrease the downstream operations needed for cultivated meat production.

摘要

基于间充质干细胞的培养肉是解决传统肉类生产所带来的生态和伦理问题的一个有前景的方案,因为与其他任何培养肉产品来源(包括植物、细菌和真菌)相比,它的蛋白质含量和组成与原始肉类蛋白质更具可比性。尽管如此,间充质干细胞的性质和实验室行为给大规模生产带来了两个重大挑战:基因漂移和在培养中的贴壁生长。实验室中使用的培养条件使细胞受到导致基因漂移的选择压力,这可能会引发致癌基因激活和“干性”丧失。这就是为什么在培养过程中需要对细胞进行基因和功能分析,以确定在实验室中未检测到明显突变或功能丧失的情况下的最大传代次数。此外,间充质干细胞的贴壁生长可能成为其大规模生产的障碍,因为对于大容量容器来说,体积与表面积之比是有限的。多盘系统、滚瓶和微载体已被提议作为扩大培养肉所需贴壁细胞生产规模的潜在解决方案。解决培养肉生产安全问题和大规模障碍的最有前景的方案是基于基因分析确定传代次数限制,以及使用可食用材料的微载体来最大化体积与表面积比例,并减少培养肉生产所需的下游操作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad8/10493286/02fb83b8ec3a/fnut-10-1189664-g001.jpg

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