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用于iPSC培养的随机生物系统模型模型

Hua Zheng¹, Sarah W Harcum², Jinxiang Pei¹

¹Mechanical and Industrial Engineering, Northeastern University, Boston, MA, 02115, USA.

Communications biology

|January 8, 2024

概括

由于细胞聚合,制造诱导多能干细胞 (iPSC) 是一个挑战. 一个新的生物系统系统 (Bio-SoS) 模型解决了iPSC培养中的营养和废物问题,改善了细胞疗法生产.

科学领域:

生物技术是生物技术.
细胞生物学细胞生物学
生物工程是生物工程.

背景情况:

诱导多能干细胞 (iPSC) 的大规模制造对于推进细胞疗法和再生医学至关重要.
iPSCs聚合在悬浮生物反应器中,导致核心细胞中营养缺乏和废物积累.
微环境的变化会导致 iPSC 种群中显著的异质性.

研究的目的:

开发一种新的生物系统系统 (Bio-SoS) 框架,用于建模iPSC聚合和微环境影响.
描述细胞对细胞的相互作用,空间和代谢异质性,以及细胞对环境变化的反应.
为优化大型iPSC制造工艺提供一个预测模型.

主要方法:

开发了一个Bio-SoS模型,整合了随机代谢反应网络,聚合动力学和反应扩散机制.
在细胞,总和和人口层面上建模因果相互依赖.
整合了一个模块化设计,用于跨不同培养系统 (单层和聚合) 的数据集成.

主要成果:

生物-SoS模型有效地描述了iPSC聚合物的细胞间相互作用和异质性.
该框架量化了诸如总体尺寸等因素对细胞健康和产品质量的影响.
对单层和聚合 iPSC 培养过程的预测得到了改善.

结论:

拟议的Bio-SoS框架提供了一种强有力的方法,以了解和减轻大型iPSC制造中的异质性.
这种建模策略可以指导生物反应器条件的优化,以提高治疗应用的细胞产品质量.
差异分解分析为影响细胞质量异质性的因素提供了关键的见解.

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