Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges

Abstract

Traditional cell culture and animal models utilized for preclinical drug screening have led to high attrition rates of drug candidates in clinical trials due to their low predictive power for human response. Alternative models using human cells to build in vitro biomimetics of the human body with physiologically relevant organ-organ interactions hold great potential to act as "human surrogates" and provide more accurate prediction of drug effects in humans. This review is a comprehensive investigation into the development of tissue-engineered human cell-based microscale multiorgan models, or multiorgan microphysiological systems for drug testing. The evolution from traditional models to macro- and microscale multiorgan systems is discussed in regards to the rationale for recent global efforts in multiorgan microphysiological systems. Current advances in integrating cell culture and on-chip analytical technologies, as well as proof-of-concept applications for these multiorgan microsystems are discussed. Major challenges for the field, such as reproducibility and physiological relevance, are discussed with comparisons of the strengths and weaknesses of various systems to solve these challenges. Conclusions focus on the current development stage of multiorgan microphysiological systems and new trends in the field.

From organotypic culture to body‐on‐a‐chip: A neuroendocrine perspective

“…Cell culture Tixier-Vidal et al 35 May et al 133 Mulder et al 128 Bohorquez et al 117 Scharrer 14 Dreifuss & Gahwiler 36 Suter et al 64…”

“…A principal need to advance body-on-chip methodologies, just as for organ-onchip, is to include the cellular heterogeneity of the natural tissue in the body-on-chip platforms, thereby allowing for more general use of these systems in addressing biological questions 128. Engineering challenges remain to address validated physiological parameters needed for each organ and in the media and microfluidics that connect them.…”

Multiorgan microfluidic platform with breathable lung chamber for inhalation or intravenous drug screening and development

“…Microfluidic organ‐on‐a‐chip systems have been introduced to replicate some of the cellular and organ to organ interactions that can occur when a body is exposed to pharmaceuticals (Esch, King, & Shuler, ; Wang, Carmona, Hickman, & Shuler, ; Wang et al, ). These devices can be modified to contain a breathable lung device to study lung physiology, disease, drug therapy and potentially inhalation drug therapy.…”

“…Microfluidic organ-on-a-chip systems have been introduced to replicate some of the cellular and organ to organ interactions that can occur when a body is exposed to pharmaceuticals (Esch, King, & Shuler, 2011;Wang, Carmona, Hickman, & Shuler, 2018;Wang et al, 2017).…”

Advances and Current Challenges Associated with the Use of Human Induced Pluripotent Stem Cells in Modeling Neurodegenerative Disease

“…The establishment of 3+ cell or tissue types within controlled in vitro platforms is relatively rare but it is an exciting area of current research due to their potential to model complex tissue-tissue interplay. The development of these so-called organs-onchips is a rapidly evolving field within bioengineering and is reviewed in detail elsewhere [Huh et al, 2012;Wang et al, 2018b]. The capacity for such systems to model complex neurological function has yet to be demonstrated but remains a tantalizing prospect for future research as our ability to generate more complex models increases.…”