Abstract
Simple SummaryOrganoids, also known as self-organized 3D organ-like clusters, represent almost a physiological system for studying cells, stem cells, tissues, and diseases, especially cancer. Microfluidic organ-on-a-chip technology has gained beneficial interest in recent years due to its potential to be a pioneer in developing personalized treatments with a precise control of many parameters such as flow conditions and nutrient supply in a microscale. Further, the dynamic nature of such personalized systems also relies on the ability to easily combine the read-outs from blood samples, urine samples, biopsies, and primary tissues. This fast-evolving innovative technology precisely fit with the concept of precision medicine, which holds an infinite potential for personalized cancer treatments.Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.
Highlights
Huang et al showed that Wnt3a, Retinoic acid, bone morphogenetic protein (BMP) as well as TGF- and Notch signaling pathway inhibitors should be added to the R-spondin culture system to activate the Wnt signaling pathway and promote the differentiation of the progenitor cells to provide a long term culture of human pluripotent stem cell- and patient-derived pancreatic cancer organoids [48]
These synthetic extracellular matrix (ECM) consist of poly-ethylene glycol (PEG)-macromers modified with ECM-binding peptides and integrin-binding peptides that cross-link with matrix metalloprotease (MMP) degradation-sensitive peptides, which support the growth and formation of endometrial epithelial organoids from single cells [70]
Lamers et al, Zang et al, and Zhou et al have demonstrated that human intestinal organoids, which were established from human adult stem cells, support severe acute respiratory syndrome (SARS) -CoV-2 replication [111,112]
Summary
Most of the current studies on cell and tissue regulation have relied on analyses of cells grown in a monolayer or suspension cell-culture models that fail to emulate the in vivo cellular micro-environment, lead to a rapid loss of function and de-differentiation [1]. An innovative three-dimensional (3D) model, has expeditiously increased in recent years and has become widespread by eliminating the gap between two-dimensional cultures and in vivo physiology. These self-organized organ-like-clusters could be derived from a variety of multipotent stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), adult stem cells, primary cells, as well as tumor cells in the 3D culture system and substantially mimic the organs from which they were derived, both in organization and in function
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