Regenerating the kidney using human pluripotent stem cells and renal progenitors

ABSTRACT

Introduction: Chronic kidney disease is a major health-care problem worldwide and its cost is becoming no longer affordable. Indeed, restoring damaged renal structures or building a new kidney represents an ambitious and ideal alternative to renal replacement therapy. Streams of research have explored the possible application of pluripotent stem cells (SCs) (embryonic SCs and induced pluripotent SCs) in different strategies aimed at regenerate functioning nephrons and at understanding the mechanisms of kidney regeneration.

Areas covered: In this review, we will focus on the main potential applications of human pluripotent SCs to kidney regeneration, including those leading to rebuilding new kidneys or part of them (organoids, scaffolds, biological microdevices) as well as those aimed at understanding the pathophysiological mechanisms of renal disease and regenerative processes (modeling of kidney disease, genome editing). Moreover, we will discuss the role of endogenous renal progenitors cells in order to understand and promote kidney regeneration, as an attractive alternative to pluripotent SCs.

Expert opinion: Opportunities and pitfalls of all these strategies will be underlined, finally leading to the conclusion that a deeper knowledge of the biology of pluripotent SCs is mandatory, in order to allow us to hypothesize their clinical application.

KEYWORDS:

• iPSCs
• kidney
• regeneration
• stem cells
• renal progenitor cells

Article Highlight

• Human pluripotent stem cells (SCs) include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). These cells can provide useful tools either to therapeutic purposes either to investigate disease pathophysiology and mechanisms, including renal diseases and kidney regeneration.

• ESCs have the advantage to be relatively quick to obtain and to be not anymore subject to licensing/royalty to be paid. Anyway, some major concerns, such as ethical issues, the high risk to degenerate in neoplasms and immunocompatibility, still remain open.

• iPSCs have the great advantage of harboring the same genetic background of the individual they are derived, thus representing an ideal tool to study the effects of genetic variants in the pathogenesis of diseases. The main risks connected with the use of iPSCs are represented by tumorigenicity and immunogenicity, the presence of an epigenetic memory, technical and economical problems related to their long turnaround time, and the presence of loyalties.

• Human pluripotent SCs have two main fields of application in kidney regeneration: they can be used to build ‘a new kidney’ or part of it by the mean of studies on organoids, scaffolds, organ-on-a-chip, and blastocyst complementation, or they can be used to investigate the mechanisms of kidney regeneration trough disease modeling and gene editing.

• Renal progenitor cells represent an attractive alternative either to study or to modulate kidney regeneration, providing important advantages in the field.

• A deeper knowledge of the biology of pluripotent SCs is mandatory, in order to allow us to hypothesize their clinical application.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This project has received funding from the European Research Council (ERC) under theEuropean Union’s Horizon 2020 research and innovation programme (grant agreement N° 648274) to P.R. and from the Tuscan Region to the Meyer Children’s Hospital ‘Programma attuativo regionale Fas-FSC (SMART)’