Controlling Differentiation of Stem Cells for Developing Personalized Organ‐on‐Chip Platforms

Abstract

Organ‐on‐chip (OOC) platforms have attracted attentions of pharmaceutical companies as powerful tools for screening of existing drugs and development of new drug candidates. OOCs have primarily used human cell lines or primary cells to develop biomimetic tissue models. However, the ability of human stem cells in unlimited self‐renewal and differentiation into multiple lineages has made them attractive for OOCs. The microfluidic technology has enabled precise control of stem cell differentiation using soluble factors, biophysical cues, and electromagnetic signals. This study discusses different tissue‐ and organ‐on‐chip platforms (i.e., skin, brain, blood–brain barrier, bone marrow, heart, liver, lung, tumor, and vascular), with an emphasis on the critical role of stem cells in the synthesis of complex tissues. This study further recaps the design, fabrication, high‐throughput performance, and improved functionality of stem‐cell‐based OOCs, technical challenges, obstacles against implementing their potential applications, and future perspectives related to different experimental platforms.

Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies

“…Starting with 2D static cell cultures, they are a staple for many applications like toxicity or metabolism analysis [38,41]. These systems are well known, with extensive literature allowing to critically analyse the data obtained, and understand the cell behaviour in many conditions [40].…”

“…More importantly, there is a failure to properly replicate and reproduce key aspects of the BBB microenvironment, including cell-cell and cell-ECM interactions that occur within the NVU [34,41]. In addition, they are restricted in supplying suitable electrical, mechanical and chemical cues, which can lead to subtle differences in barrier permeability and cell morphology when compared to in vivo models [41]. Even though the realism of 2D cultures can be somewhat improved by incorporating more cell types or by using human cells, robustness is sacrificed, and thus, these models are not appropriate when the intention is to model higher order features and trajectories of the CNS [38].…”

“…3D cell systems have garnered attention for decades, being introduced as an attempt to better represent the intricate human physiology and relevant conditions, therefore allowing to improve the simulation of the in vivo setting of cells inside organs and tissues [32,41]. Traditional 3D cultures are usually achieved by culturing cells on biocompatible extracellular scaffolds (such as hydrogels), either in well plates or on Transwell ® membranes [32,34].…”

Skin Tissue Substitutes and Biomaterial Risk Assessment and Testing

“…Substantial efforts have been made in recent years to model and create substitutes that mimic human skin, placing the skin amongst the most developed in vitro engineered constructs. Since it is the body's first barrier being exposed to many types of cosmetics and therapeutics, extensive funding has been allocated by different industries for in vitro skin modulation in an effort to end continuous legal and ethical issues regarding product testing on skin (Karimi et al, 2016 ; Geraili et al, 2017 ). The in vitro modeling of the human skin can be divided into two main streams in terms of research motivation (Mathes et al, 2014 ).…”

Engineering in-vitro stem cell-based vascularized bone models for drug screening and predictive toxicology

“…Novel studies are exploring the incorporation of other molecules, such as KR-34893 indene compound that stimulates MSC differentiation and mineral deposition [ 160 ], oxygen-releasing agents like calcium peroxide to solve O 2 diffusion issues [ 160 ], and platelet-rich fibrin to stimulate bone marrow-derived MSC differentiation [ 160 ]. AM and 3D-printing technologies have also produced great advancements in the field of microfluidics systems and organ-tissue chips that employ stem cells for in-vitro disease modeling and drug screening [ 161 – 163 ]. In-vitro vascularized bone models have steadily benefited from this technology.…”