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1.
Stem Cell Reports ; 19(5): 604-617, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38670111

RESUMO

Cell culture technology has evolved, moving from single-cell and monolayer methods to 3D models like reaggregates, spheroids, and organoids, improved with bioengineering like microfabrication and bioprinting. These advancements, termed microphysiological systems (MPSs), closely replicate tissue environments and human physiology, enhancing research and biomedical uses. However, MPS complexity introduces standardization challenges, impacting reproducibility and trust. We offer guidelines for quality management and control criteria specific to MPSs, facilitating reliable outcomes without stifling innovation. Our fit-for-purpose recommendations provide actionable advice for achieving consistent MPS performance.


Assuntos
Técnicas de Cultura de Células , Humanos , Reprodutibilidade dos Testes , Técnicas de Cultura de Células/métodos , Controle de Qualidade , Organoides/citologia , Sistemas Microfisiológicos
2.
Front Med (Lausanne) ; 8: 728866, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589503

RESUMO

The first concepts for reproducing human systemic organismal biology in vitro were developed over 12 years ago. Such concepts, then called human- or body-on-a-chip, claimed that microphysiological systems would become the relevant technology platform emulating the physiology and morphology of human organisms at the smallest biologically acceptable scale in vitro and, therefore, would enable the selection of personalized therapies for any patient at unprecedented precision. Meanwhile, the first human organoids-stem cell-derived complex three-dimensional organ models that expand and self-organize in vitro-have proven that in vitro self-assembly of minute premature human organ-like structures is feasible, once the respective stimuli of ontogenesis are provided to human stem cells. Such premature organoids can precisely reflect a number of distinct physiological and pathophysiological features of their respective counterparts in the human body. We now develop the human-on-a-chip concepts of the past into an organismoid theory. We describe the current concept and principles to create a series of organismoids-minute, mindless and emotion-free physiological in vitro equivalents of an individual's mature human body-by an artificially short process of morphogenetic self-assembly mimicking an individual's ontogenesis from egg cell to sexually mature organism. Subsequently, we provide the concept and principles to maintain such an individual's set of organismoids at a self-sustained functional healthy homeostasis over very long time frames in vitro. Principles how to perturb a subset of healthy organismoids by means of the natural or artificial induction of diseases are enrolled to emulate an individual's disease process. Finally, we discuss using such series of healthy and perturbed organismoids in predictively selecting, scheduling and dosing an individual patient's personalized therapy or medicine precisely. The potential impact of the organismoid theory on our healthcare system generally and the rapid adoption of disruptive personalized T-cell therapies particularly is highlighted.

3.
Sci Rep ; 10(1): 7865, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398725

RESUMO

Extrapolation of cell culture-based test results to in vivo effects is limited, as cell cultures fail to emulate organ complexity and multi-tissue crosstalk. Biology-inspired microphysiological systems provide preclinical insights into absorption, distribution, metabolism, excretion, and toxicity of substances in vitro by using human three-dimensional organotypic cultures. We co-cultured a human lung equivalent from the commercially available bronchial MucilAir culture and human liver spheroids from HepaRG cells to assess the potential toxicity of inhaled substances under conditions that permit organ crosstalk. We designed a new HUMIMIC Chip with optimized medium supply and oxygenation of the organ cultures and cultivated them on-chip for 14 days in separate culture compartments of a closed circulatory perfusion system, demonstrating the viability and homeostasis of the tissue cultures. A single-dose treatment of the hepatotoxic and carcinogenic aflatoxin B1 impaired functionality in bronchial MucilAir tissues in monoculture but showed a protective effect when the tissues were co-cultured with liver spheroids, indicating that crosstalk can be achieved in this new human lung-liver co-culture. The setup described here may be used to determine the effects of exposure to inhaled substances on a systemic level.


Assuntos
Aflatoxina B1/farmacologia , Técnicas de Cocultura/métodos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Técnicas de Cultura de Órgãos/métodos , Esferoides Celulares/efeitos dos fármacos , Administração por Inalação , Apoptose/efeitos dos fármacos , Brônquios/citologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/citologia , Fígado/metabolismo , Pulmão/citologia , Pulmão/metabolismo , Venenos/farmacologia , Substâncias Protetoras/farmacologia , Esferoides Celulares/citologia , Esferoides Celulares/metabolismo
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