Marx Uwe, Accastelli Enrico, David Rhiannon, Erfurth Hendrik, Koenig Leopold, Lauster Roland, Ramme Anja Patricia, Reinke Petra, Volk Hans-Dieter, Winter Annika, Dehne Eva-Maria
Department of Medical Biotechnology, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
TissUse GmbH, Berlin, Germany.
Front Med (Lausanne). 2021 Sep 13;8:728866. doi: 10.3389/fmed.2021.728866. eCollection 2021.
The first concepts for reproducing human systemic organismal biology 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 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 -have proven that 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 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 . 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.
再现人类全身机体生物学的最初概念是在12多年前提出的。当时这类概念被称为人体芯片，宣称微生理系统将成为在最小生物学可接受尺度上模拟人类生物体生理和形态的相关技术平台，因此能够以前所未有的精度为任何患者选择个性化疗法。与此同时，首批类器官——由干细胞衍生的复杂三维器官模型，能够生长和自我组织——已证明，一旦将个体发育的相应刺激提供给人类干细胞，微小的早产人类器官样结构的自我组装是可行的。这类早产类器官能够精确反映其在人体中相应对应物的许多不同生理和病理生理特征。我们现在将过去的人体芯片概念发展为类生物体理论。我们描述了当前通过模仿个体从卵细胞到性成熟生物体的个体发育过程的形态发生自我组装的人工短过程，创建一系列类生物体——个体成熟人体的微小、无思维和无情感的生理等效物——的概念和原则。随后，我们提供了在很长时间内将这类个体的类生物体维持在自我维持的功能健康稳态的概念和原则。还纳入了如何通过自然或人工诱导疾病来干扰一部分健康类生物体的原则，以模拟个体的疾病过程。最后，我们讨论了如何使用这类健康和受干扰的类生物体来精确预测性地选择、安排和确定个体患者的个性化治疗或药物剂量。强调了类生物体理论对我们整个医疗保健系统的潜在影响，特别是对颠覆性个性化T细胞疗法的快速采用的影响。
