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Review
. 2022 Jan;33(1):15-32.
doi: 10.1681/ASN.2021081073. Epub 2021 Nov 17.

Regrow or Repair: An Update on Potential Regenerative Therapies for the Kidney

Melissa H Little  1   2   3 , Benjamin D Humphreys  4   5
Affiliations
Review

Regrow or Repair: An Update on Potential Regenerative Therapies for the Kidney

Melissa H Little et al. J Am Soc Nephrol. 2022 Jan.

Abstract

Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.

Keywords: directed differentiation; gene editing; kidney development; pluripotent stem cell; regenerative therapies; single-cell expression profiling; stem cell; tissue repair.

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Figures

Figure 1.
Figure 1.
Original diagram of renal regeneration options illustrating proposed approaches to organ repair, including in situ kidney repair and ex vivo renal stem cell approaches, or de novo regenerative options.
Figure 2.
Figure 2.
Contemporary view of options available for regenerative therapies in the kidney, highlighting the technology advances that have underpinned these areas of research.
Figure 3.
Figure 3.
Summary of our current understanding of responses to kidney injury. (A) Pseudotemporal ordering of proximal tubule (PT) cells during injury and repair on the basis of mouse scRNA-seq data reveal distinct trajectories: successful repair (green) and failed repair (blue). The failed repair cell state does not simply represent ongoing acute injury because the failed repair cell state is characterized by expression of a group of genes that are never expressed in cells that undergo successful repair. Data are from Kirita et al. (B) Model for successful versus failed repair. Although the majority of PT epithelia successfully repair after acute injury, a minority adopts a failed repair cell state characterized by increased NFκB activity and the secretion of a variety of proinflammatory and profibrotic cytokines. Figure created with BioRender.com.
Figure 4.
Figure 4.
Illustration of how human stem cell–derived kidney organoids and cell types may be used for disease modeling or regenerative therapies. hPSCs can be derived from the inner cell mass (ICM) of a human blastocyst or via direct reprogramming from any adult somatic cell, including cells from a patient who has a known mutation or VOUS detected using next generation sequencing. The resulting hPSCs can be gene edited using CRISPR/Cas9 to correct putative patient mutations, introduce novel mutations, or create modified cells that read out cellular state or identity. The generation of kidney organoids is possible via the directed differentiation of hPSCs based upon our understanding of development. Such kidney organoids are being evaluated for maturation and function post-transplantation in immunocompromised mouse models to optimize tissue for renal replacement. Individual cell types can be generated from iPSCs or isolated from kidney organoids for use in drug screening or as a cell source in biodevices. Finally, hPSC-derived models of the kidney or specific kidney cell types can be used as human models of disease for the development of drugs. Generated using BioRender.com.
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References

    1. Luyckx VA, Tonelli M, Stanifer JW: The global burden of kidney disease and the sustainable development goals. Bull World Health Organ 96: 414–422D, 2018. 10.2471/blt.17.206441 - DOI - PMC - PubMed
    1. Barker CF, Markmann JF: Historical overview of transplantation. Cold Spring Harb Perspect Med 3: a014977, 2013. 10.1101/cshperspect.a014977 - DOI - PMC - PubMed
    1. Harrison JH, Merrill JP, Murray JE: Renal homotransplantation in identical twins. Surg Forum 6: 432–436, 1956 - PubMed
    1. Starzl TE, Marchioro TL, Waddell WR: The reversal of rejection in human renal homografts with subsequent development of homograft tolerance. Surg Gynecol Obstet 117: 385–395, 1963 - PMC - PubMed
    1. Watts G: Willem Johan Kolff. Lancet 373: 1168, 2009. 10.1016/S0140-6736(09)60673-5 - DOI

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