The Regenerative Potential of Human Adult Renal Stem/Progenitor Cells

Sallustio, Fabio; Picerno, Angela; Giannuzzi, Francesca; Montenegro, Francesca; Franzin, Rossana; Gesualdo, Loreto

doi:10.1007/978-981-99-0846-2_24-1

Fabio Sallustio^2,3,
Angela Picerno⁴,
Francesca Giannuzzi⁴,
Francesca Montenegro^4,5,
Rossana Franzin^2,3 &
…
Loreto Gesualdo^2,3

38 Accesses

Abstract

The human adult renal stem/progenitor cells (ARPCs) play a role in renal regeneration in two ways: by differentiating directly or by secreting reparative molecules. They can differentiate into epithelial, endothelial, osteogenic, and adipogenic cells. ARPCs can regenerate long segments of renal tubules and also missing podocytes in cortical nephrons after acute kidney injury (AKI). These renal progenitors express the Toll-Like Receptor 2 (TLR2); they are activated by TLR2 ligands and can secrete restorative and therapeutic factors capable of repairing renal tubular cells damaged. The TLR2 can act as a damaged sensor, and its activation can cause stem cell proliferation and differentiation, among other things. Kidney progenitors can repair physical and chemical damage, such as a wound in epithelial tissue or damage caused by cisplatin, a widely used chemotherapy drug that can cause nephrotoxic side effects. Following renal tubular cell damage, ARPCs release inhibin-A and decorin, which are directly involved in cell regeneration. The ARPCs can also prevent endothelial dysfunction and protect the endothelial compartment following exposure to lipopolysaccharides (LPS), thus promoting kidney repair. They exert an anti-fibrotic effect through the secretion of antiseptic molecules CXCL6, SAA4, and BPIFA2. Moreover, ARPCs possess immunomodulatory capabilities towards CD3+ CD4-CD8- (double negative; DN) T-lymphocytes and can promote regulatory T lymphocytes (Treg). In addition, it has been discovered that renal progenitors, thanks to the high expression of HOTAIR, can secrete high quantities of α-Klotho, an anti-aging protein capable of influencing the surrounding tissues and therefore modulating renal aging. These data open new perspectives on treating diseases, suggesting an underestimated role of ARPCs in preventing and repairing kidney injuries and novel strategies to protect the endothelial compartment and promote kidney repair.

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Abbreviations

AKI:: Acute kidney injury
APOL1:: Apolipoprotein L1
ARPC:: Adult Renal Progenitor Cells
BMP:: Bone morphogenetic protein
CD:: Collecting ducts
CM:: Cap mesenchyme
DAMP:: Damage-Associated Molecular Patterns
ESCs:: Epidermal stem cells
FGF:: Fibroblast Growth Factor
HGF:: Hepatocyte Growth Factor
IDO:: Indoleamine-pyrrole 2,3-dioxygenase
IgAN:: IgA Nephropathy
IM:: Intermediate mesoderm
iNOS:: Inducible Nitric Oxide Synthase
LTA:: Lipoteichoic acid
MM:: Metanephric mesenchyme
MSCs:: Mesenchymal stem cells
PAMP:: Pathogen-Associated Molecular Patterns
Pax2:: Paired box gene 2
PGE2:: Prostaglandin E2
PRTEC:: Proximal renal tubule epithelial cells
RV:: Renal vesicles
SCID:: Severe combined immunodeficient
SM:: Stromal mesenchyme
TERT:: Telomerase reverse transcriptase
TGF:: Transforming growth factor- β1
TLR2:: Toll-like receptor 2
TNF:: Tumor Necrosis Factor
UB:: Ureteric bud

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Department of Precision and Regenerative Medicine and Ionian Area, Università degli Studi di Bari Aldo Moro, Bari, Italy
Fabio Sallustio, Rossana Franzin & Loreto Gesualdo
MIRROR-Medical Institute for Regeneration, Repairing and Organ Replacement, Interdepartmental Center, University of Bari, Bari, Italy
Fabio Sallustio, Rossana Franzin & Loreto Gesualdo
Department of Interdisciplinary Medicine, University of Bari, Bari, Italy
Angela Picerno, Francesca Giannuzzi & Francesca Montenegro
PersonGene – Academic spinoff of the University of Bari, Bari, Italy
Francesca Montenegro

Authors

Fabio Sallustio
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Angela Picerno
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Francesca Giannuzzi
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Francesca Montenegro
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Rossana Franzin
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Loreto Gesualdo
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Corresponding author

Correspondence to Fabio Sallustio .

Editor information

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Department of Basic Sciences, Sulaiman Alrajhi University, AlQaseem, Saudi Arabia
Khawaja H. Haider

Section Editor information

Basic Sciences Department, Sulaiman AlRajhi University, AlQaseem, Saudi Arabia
Khawaja Husnain Haider Ph.D
Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Bari, Italy
Fabio Sallustio
MIRROR-Medical Institute for Regeneration, Repairing and Organ Replacement, Interdepartmental Center, University of Bari Aldo Moro, Bari, Italy
Fabio Sallustio
University of Alberta Director Clinical Islet and Living Donor Liver Transplant Program, University of Alberta, Edmonton, Canada
A. M. James Shapiro

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Sallustio, F., Picerno, A., Giannuzzi, F., Montenegro, F., Franzin, R., Gesualdo, L. (2023). The Regenerative Potential of Human Adult Renal Stem/Progenitor Cells. In: Haider, K.H. (eds) Handbook of Stem Cell Applications. Springer, Singapore. https://doi.org/10.1007/978-981-99-0846-2_24-1

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DOI: https://doi.org/10.1007/978-981-99-0846-2_24-1
Received: 24 February 2023
Accepted: 19 March 2023
Published: 10 August 2023
Publisher Name: Springer, Singapore
Print ISBN: 978-981-99-0846-2
Online ISBN: 978-981-99-0846-2
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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