Regenerating the kidney using human pluripotent stem cells and renal progenitors

Becherucci, Francesca; Mazzinghi, Benedetta; Allinovi, Marco; Angelotti, Maria Lucia; Romagnani, Paola

doi:10.1080/14712598.2018.1492546

Cited by 25 publications

(23 citation statements)

References 118 publications

(159 reference statements)

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“…On the other hand, attempts are continuing to develop approaches for affecting resident progenitor cells, for example, to increase the activity of glomerular parietal cells, which are known to be progenitors of podocytes. Some compounds, such as glycogen synthase kinases 3-α and -β (GSK3s) inhibitor 6-bromoindirubin-3-oxime (BIO) [131], notch signaling inhibitors [132], interferon [133], steroids [134], and some others enhanced the proliferation of parietal cells and mediated their differentiation into podocytes in vitro [135]. Perhaps, compounds exist that would selectively affect STC or other possible pools of progenitor cells.…”

Section: Potential Approaches Affecting Kidney Regenerationmentioning

confidence: 99%

Kidney Cells Regeneration: Dedifferentiation of Tubular Epithelium, Resident Stem Cells and Possible Niches for Renal Progenitors

Andrianova

Buyan

Zorova

et al. 2019

IJMS

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A kidney is an organ with relatively low basal cellular regenerative potential. However, renal cells have a pronounced ability to proliferate after injury, which undermines that the kidney cells are able to regenerate under induced conditions. The majority of studies explain yielded regeneration either by the dedifferentiation of the mature tubular epithelium or by the presence of a resident pool of progenitor cells in the kidney tissue. Whether cells responsible for the regeneration of the kidney initially have progenitor properties or if they obtain a “progenitor phenotype” during dedifferentiation after an injury, still stays the open question. The major stumbling block in resolving the issue is the lack of specific methods for distinguishing between dedifferentiated cells and resident progenitor cells. Transgenic animals, single-cell transcriptomics, and other recent approaches could be powerful tools to solve this problem. This review examines the main mechanisms of kidney regeneration: dedifferentiation of epithelial cells and activation of progenitor cells with special attention to potential niches of kidney progenitor cells. We attempted to give a detailed description of the most controversial topics in this field and ways to resolve these issues.

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Section: Potential Approaches Affecting Kidney Regenerationmentioning

confidence: 99%

Kidney Cells Regeneration: Dedifferentiation of Tubular Epithelium, Resident Stem Cells and Possible Niches for Renal Progenitors

Andrianova

Buyan

Zorova

et al. 2019

IJMS

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“…The high proliferative and differentiation capacity of pluripotent stem cells has meant that there has been a significant research focussed on the potential therapeutic benefit of iPSCs. However, caution should still be employed due to the presence of epigenetic memory [72,73], and also, abnormal programming and the accumulation of somatic mutations may promote tumorigenesis and immunogenicity [74,75].…”

Section: Innate Kidney Repair and The Influence Of Stem Cellsmentioning

confidence: 99%

“…Although complete kidney regeneration using SCs remains elusive, small yet complex kidney structures with renal-specific functions, referred to as organoids, have been developed as a way of potentially replacing renal function [75]. Organoids are capable of spontaneous organisation into structures resembling nephron segments, glomeruli, interstitium, and collecting ducts [149,154,156,[172][173][174] akin to the embryonic kidney.…”

Section: Bioprinting Alternatives: Self-assembling Organoid Formationmentioning

confidence: 99%

“…Since kidney organoids are predominantly comprised of a single cell type in a 3D matrix, they are currently limited to the study of kidney disease and injury [175][176][177], drug nephrotoxicity [178,179], and kidney development [156,172], since they are incapable of replicating the varied functionality of a kidney. Thus, the ability to restore renal structures and engineer new kidney tissues remains extremely ambitious [75], not least since the kidney is inherently unable to regenerate new nephrons in vivo. Despite this, iPSC-derived organoids may potentially be utilised in alternative bioengineering approaches; distinct renal cells isolated from iPSC kidney organoids may be useful for generating sufficient numbers of cells for populating biologic or artificial tissue scaffolds and matrices [165].…”

Section: Bioprinting Alternatives: Self-assembling Organoid Formationmentioning

confidence: 99%

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A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations

2019

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The widening gap between organ availability and need is resulting in a worldwide crisis, particularly concerning kidney transplantation. Regenerative medicine options are becoming increasingly advanced and are taking advantage of progress in novel manufacturing techniques, including 3D bioprinting, to deliver potentially viable alternatives. Cell-integrated and wearable artificial kidneys aim to create convenient and efficient systems of filtration and restore elements of immunoregulatory function. Whilst preliminary clinical trials demonstrated promise, manufacturing and trial design issues and identification of suitable and sustainable cell sources have shown that more development is required for market progression. Tissue engineering and advances in biomanufacturing techniques offer potential solutions for organ shortages; however, due to the complex kidney structure, previous attempts have fallen short. With the recent development and progression of 3D bioprinting, cell positioning and resolution of material deposition in organ manufacture have never seen greater control. Cell sources for constructing kidney building blocks and populating both biologic and artificial scaffolds and matrices have been identified, but in vitro culturing and/or differentiation, in addition to maintaining phenotype and viability during and after lengthy and immature manufacturing processes, presents additional problems. For all techniques, significant process barriers, clinical pathway identification for translation of models to humans, scaffold material availability, and long-term biocompatibility need to be addressed prior to clinical realisation.

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“…TE strategies combine supporting scaffolds, of either natural or biodegradable polymers, or decellularized kidneys with different kinds of SCs and growth factors, to generate organoids, implantable renal assist devices, or transplantable organs [2][3][4][5]. On the other hand, RM approaches rely on the direct administration of different types of SCs, such as embryonic SCs (ESCs) [6][7][8], inducible pluripotent SCs (iPSCs), fetal SCs (FSCs), amniotic fluid-derived SCs [9], or adult SCs [10], to aid renal regeneration in the context of both acute kidney injury and chronic kidney disease [11]. In both cases, demand is increasing for alternative cell sources that overcome the ethical and legal issues accompanying the application of ESCs and FSCs, devoid of the mutational effects associated with iPSCs, and of autologous origin.…”

Section: Introductionmentioning

confidence: 99%

Substrate Stiffness Modulates Renal Progenitor Cell Properties via a ROCK-Mediated Mechanotransduction Mechanism

Melica

Regina

Parri

et al. 2019

Cells

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Stem cell (SC)-based tissue engineering and regenerative medicine (RM) approaches may provide alternative therapeutic strategies for the rising number of patients suffering from chronic kidney disease. Embryonic SCs and inducible pluripotent SCs are the most frequently used cell types, but autologous patient-derived renal SCs, such as human CD133+CD24+ renal progenitor cells (RPCs), represent a preferable option. RPCs are of interest also for the RM approaches based on the pharmacological encouragement of in situ regeneration by endogenous SCs. An understanding of the biochemical and biophysical factors that influence RPC behavior is essential for improving their applicability. We investigated how the mechanical properties of the substrate modulate RPC behavior in vitro. We employed collagen I-coated hydrogels with variable stiffness to modulate the mechanical environment of RPCs and found that their morphology, proliferation, migration, and differentiation toward the podocyte lineage were highly dependent on mechanical stiffness. Indeed, a stiff matrix induced cell spreading and focal adhesion assembly trough a Rho kinase (ROCK)-mediated mechanism. Similarly, the proliferative and migratory capacity of RPCs increased as stiffness increased and ROCK inhibition, by either Y27632 or antisense LNA-GapmeRs, abolished these effects. The acquisition of podocyte markers was also modulated, in a narrow range, by the elastic modulus and involved ROCK activity. Our findings may aid in 1) the optimization of RPC culture conditions to favor cell expansion or to induce efficient differentiation with important implication for RPC bioprocessing, and in 2) understanding how alterations of the physical properties of the renal tissue associated with diseases could influenced the regenerative response of RPCs.

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Regenerating the kidney using human pluripotent stem cells and renal progenitors

Cited by 25 publications

References 118 publications

Kidney Cells Regeneration: Dedifferentiation of Tubular Epithelium, Resident Stem Cells and Possible Niches for Renal Progenitors

Kidney Cells Regeneration: Dedifferentiation of Tubular Epithelium, Resident Stem Cells and Possible Niches for Renal Progenitors

A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations

Substrate Stiffness Modulates Renal Progenitor Cell Properties via a ROCK-Mediated Mechanotransduction Mechanism

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