Insight into Development, Function and Pathologies from Human Induced Pluripotent Stem Cells LIKE (Liver, Intestinal and Kidney Epithelium) Derived Models

About this Research Topic

Background

Liver, intestine and kidneys present an epithelium largely involved in molecular transport including nutrients, xenobiotics, ions and even drugs. Because these functions are crucial in maintaining the body homeostasis, barrier dysfunction will lead to unpresented diseases that will impact both organ and body. It is well described that epithelial functions are modulated and regulated through intricate interactions with other specialized cells types present in the vicinity. Therefore, understanding the physiology of such structures must rely on the study of the whole organ as well as each independent cell type.

Our knowledge on liver, intestine and kidneys has mostly been drawn from established vertebrate and cellular models. While classical cell biology brought input to understand each cell types independently, animal models and medical/clinical studies allowed us to depict a more integrated view of processes involved in their regulations. With this in mind, human induced pluripotent stem cells (hiPSCs) brought us a new angle to refine our understanding. Indeed, because they display features close from embryonic stem cells, they can theoretically give rise to any cells of the human body in vitro, giving the opportunity to study their development, and understand mechanisms that lead to such specific functions. Moreover, because hiPSCs can be reprogrammed from human somatic cells, it gives an unprecedented opportunity to study cells carrying endogenous mutations or genomic environment linked to defined pathologies in a human context. In addition to provide an additional tool to investigate molecular mechanisms involved in a given pathology, this in vitro model is an excellent candidate for drug screening and the development of strategies for therapeutical applications.

Yet limitations in differentiated hiPSCs remain. For years, differentiation protocols relied on two-dimensions monolayer of cells from one specific phenotype leading to differentiated cells displaying lack of maturation and in some extent function compared to their adult counterpart. Importantly, cells were matured in absence of physical and biological environment, which lead to organ maturation in vivo. These limits of classical cell biology have now been largely pushed through the addition of a third dimension, by adding flow dynamic or, through multicellular/environmental interactions with the development of organoïds. But these advances are moving the field forward from a translational standpoint?

Keywords: human pluripotent stem cells, organoid, gastrointestinal, liver, kidney

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