Abstract
Kidney organoids derived from pluripotent stem cells became a real alternative to the use of in vitro cellular models or in vivo animal models. Indeed, the comprehension of the key steps involved during kidney embryonic development led to the establishment of protocols enabling the differentiation of pluripotent stem cells into highly complex and organized structures, composed of various renal cell types. These organoids are linked with one major application based on iPSC technology advantage: the possibility to control iPSC genome, by selecting patients with specific disease or by genome editing tools such as CRISPR/Cas9 system. This allows the generation of kidney organoïds which recapitulate important physiopathological mechanisms such as cyst formation in renal polycystic disease for example. This review will focus on studies combining these both cutting edge technologies i.e., kidney organoid differentiation and genome editing and will describe what are the main advances performed in the comprehension of physiopathological mechanisms of renal diseases, as well as discuss remaining technical barriers and perspectives in the field.
Highlights
In nephrology, all commonly used models in fundamental and translational research have their own limits: in vitro models are restricted to one cell type analysis without consideration of the intercellular and environmental interactions within the tissue
In order to mimic spatial gradients existing in the in situ kidney development, placing in contact one side of the organoid with beads releasing BMP4 induces the geo-specific differentiation of cells that are close to it toward “ureter-like” cells of the collecting tube, allowing to break the symmetry of the organoid by raising its anatomical realism [12]
CRISPR technology has been used to develop a system in which renal differentiation, glomerular maturation, and podocyte phenotype can be evaluated within organoids by fluorescence microscopy using reporter genes and the extinction of NPHS expression [40]
Summary
All commonly used models in fundamental and translational research have their own limits: in vitro models are restricted to one cell type analysis without consideration of the intercellular and environmental interactions within the tissue. From the isolated organ to the whole organism, are integrative, physiological, and predictive but each individual from an experimental group can react differently to the same treatment, leading to non-negligible bias, in addition to high time and cost aspects. Ethical laws are limiting the use of living animals for scientific purposes. Evolution toward one intermediary model is a necessity; kidney organoids derived from pluripotent stem cells are one judicious alternative to this issue
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