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器官芯片对药物开发现代化的生物伦理影响。

Bioethical implications of organ-on-a-chip on modernizing drug development.

机构信息

Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.

Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Artif Organs. 2023 Oct;47(10):1553-1558. doi: 10.1111/aor.14620. Epub 2023 Aug 14.

Abstract

Organ-on-chips are three-dimensional microdevices that emulate the structure, functionality, and behavior of specific tissues or organs using human cells. Combining organoids with microfabricated fluidic channels and microelectronics, these systems offer a promising platform for studying disease mechanisms, drug responses, and tissue performance. By replicating the in vivo microenvironment, these devices can recreate complex cell interactions in controlled conditions and facilitate research in various fields, including drug toxicity and efficacy studies, biochemical analysis, and disease pathogenesis. Integrating human induced pluripotent stem cells further enhances their applicability, thereby enabling patient-specific disease modeling for precision medicine. Although challenges like economy-of-scale, multichip integration, and regulatory compliance exist, advances in this modular technology show promise for lowering drug development costs, improving reproducibility, and reducing the reliance on animal testing. The ethical landscape surrounding organ-on-chip usage presents both benefits and concerns. While these chips offer an alternative to animal testing and potential cost savings, they raise ethical considerations related to community engagement, informed consent, and the need for standardized guidelines. Ensuring public acceptance and involvement in decision-making is vital to address misinformation and mistrust. Furthermore, personalized medicine models using patient-derived cells demand careful consideration of potential ethical dilemmas, such as modeling physiological functions of fetuses or brains and determining the extent of protection for these models. To achieve the full potential of organ-on-a-chip models, collaboration between scientists, ethicists, and regulators is essential to fulfil the promise of transforming drug development, advancing personalized medicine, and contributing to a more ethical and efficient biomedical research landscape.

摘要

器官芯片是一种三维微器件,使用人类细胞模拟特定组织或器官的结构、功能和行为。将类器官与微制造的流体通道和微电子产品相结合,这些系统为研究疾病机制、药物反应和组织性能提供了一个很有前景的平台。通过复制体内微环境,这些设备可以在受控条件下重现复杂的细胞相互作用,并促进各个领域的研究,包括药物毒性和疗效研究、生化分析和疾病发病机制。整合人类诱导多能干细胞进一步增强了它们的适用性,从而实现了针对特定患者的疾病建模,以用于精准医学。尽管存在规模经济、多芯片集成和法规遵从性等挑战,但这项模块化技术的进步有望降低药物开发成本、提高重现性并减少对动物测试的依赖。器官芯片使用所涉及的伦理问题既有好处也有担忧。虽然这些芯片提供了一种替代动物测试的方法,并具有潜在的成本节约优势,但它们引发了与社区参与、知情同意以及标准化指南的需求相关的伦理考虑。确保公众接受并参与决策制定对于解决错误信息和不信任至关重要。此外,使用患者来源细胞的个性化医学模型需要仔细考虑潜在的伦理困境,例如模拟胎儿或大脑的生理功能,以及确定对这些模型的保护程度。为了实现器官芯片模型的全部潜力,科学家、伦理学家和监管机构之间的合作至关重要,这有助于实现改变药物开发、推进个性化医学以及为更具伦理和高效的生物医学研究环境做出贡献的承诺。

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