Microphysiological modeling of the reproductive tract: a fertile endeavor.

Microphysiological modeling of the reproductive tract: a fertile endeavor.
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DOI:
10.1177/1535370214529387
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发表时间:
2014-09
期刊:
Experimental biology and medicine (Maywood, N.J.)
影响因子:
--
通讯作者:
Burdette JE
Burdette JE
中科院分区:
其他
文献类型:
--
作者:
Eddie SL;Kim JJ;Woodruff TK;Burdette JE

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动物模型的临床前毒性测试是药物开发过程的基石,但它通常无法预测人类受试者的不良反应和耐受性问题。对研究药物的物种特异性反应使研究人员利用人体组织和细胞来更好地估计人体毒性。不幸的是,人类细胞衍生的模型是不完美的,因为毒性是孤立地评估的,从正常的生理微环境中去除。微生理学建模,通常被称为“器官芯片”或“人类芯片”,将人体组织置于模拟人体体内生理学复杂性的微流体系统中,从而允许在生物学相关环境中对几种细胞类型,组织和器官进行毒性测试。在这里,我们描述的重要概念时,开发一个芯片上的复制模型。女性和男性生殖微流控系统的开发对于基于性别的体外毒性和药物测试至关重要。本文综述了体内男性和女性生殖系统的生物学和生理学方面,以及在设计微生理学人类芯片模型时应考虑的问题。此外,生殖道和其他系统之间的相互作用进行了探讨,重点是生殖道和疾病病理生理学产生的因素和激素的影响。
Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs has led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling, often referred to as ‘organ-on-a-chip’ or ‘human-on-a-chip’ places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology.
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