Review articleA strategy for generating kidney organoids: Recapitulating the development in human pluripotent stem cells

- The kidney is organized by nephron, collecting duct, endothelium and interstitium progenitor populations.
- Kidney progenitors are derived from both the anterior and posterior intermediate mesoderm.
- Recapitulating the development in hPSCs can induce both the anterior and posterior intermediate mesoderm in vitro.
- Kidney organoids developed from the hPSCs-derived intermediate mesoderm comprise all renal cell types.

Directed differentiation of human pluripotent stem cells (hPSCs) can provide us any required tissue/cell types by recapitulating the development in vitro. The kidney is one of the most challenging organs to generate from hPSCs as the kidney progenitors are composed of at least 4 different cell types, including nephron, collecting duct, endothelial and interstitium progenitors, that are developmentally distinguished populations. Although the actual developmental process of the kidney during human embryogenesis has not been clarified yet, studies using model animals accumulated knowledge about the origins of kidney progenitors. The implications of these findings for the directed differentiation of hPSCs into the kidney include the mechanism of the intermediate mesoderm specification and its patterning along with anteroposterior axis. Using this knowledge, we previously reported successful generation of hPSCs-derived kidney organoids that contained all renal components and modelled human kidney development in vitro. In this review, we explain the developmental basis of the strategy behind this differentiation protocol and compare strategies of studies that also recently reported the induction of kidney cells from hPSCs. We also discuss the characterization of such kidney organoids and limitations and future applications of this technology.

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