Generating Multiple Kidney Progenitors and Cell Types from Human Pluripotent Stem Cells

Hariharan, Krithika; Reinke, Petra; Kurtz, Armin

doi:10.1007/978-1-4939-9021-4_9

Cited by 6 publications

(1 citation statement)

References 6 publications

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“…14,29,30,31 For example, WNT activation using a GSK3β inhibitor (CHIR99021), FGF9, Activin A, Retinoic acid (RA) and BMP7 as instructive signals have been employed to derive functional podocytes, proximal renal tubules, and glomeruli. 15,32,33,34,35,36 Despite these efforts and achievements, there will always be variabilities between differentiation protocols, the maturation state of the differentiated renal cells and genes associated with temporal maturation during human kidney organoids formation from human iPSCs. 37,38 We propose that using native renal stem cells isolated directly from urine will circumvent most of the shortfalls and deficiencies associated with human pluripotent stem cell-based models.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Molecular Portrait of Human Urine-derived Renal Progenitor Cells

Rahman

Wruck

Spitzhorn

et al. 2019

Preprint

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Human urine is a non-invasive source of stem cells with regeneration potential. Here, we investigated the cellular and molecular identities, and the gene regulation driving self-renewal and differentiation of these cells in vitro. These cells express pluripotency-associated markers enabling easy reprogramming. Based on the expression of renal associated genes, proteins and functionality, we refer to these cells as urine derived renal progenitor cells-UdRPCs. CHIR99021-induced differentiation of UdRPCs activated WNT-related genes-AXIN2, JUN and NKD1. Protein interaction network identified JUN as a putative regulator of differentiation whereas self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3. Our data will enhance understanding of the molecular identities of UdRPCs, and enable the generation of renal disease models in vitro and eventually kidney-associated regenerative therapies.3 Abstract Background Human urine is now recognised as a non-invasive source of stem cells with regeneration potential. These cells are mesenchymal stem cells but their detailed molecular and cellular identities are poorly defined. Furthermore, unlike the mouse, the gene regulatory network driving self-renewal and differentiation into functional renal cells in vitro remain unresolved. MethodsWe isolated urine stem cells from 10 individuals from both genders and distinct ages, characterized them as renal progenitor cells and explored the gene regulatory network sustaining self-renewal. ResultsThese cells express pluripotency-associated proteins-TRA-1-60, TRA-1-81, SSEA4, C-KIT and CD133. Expression of pluripotency-associated proteins enabled rapid reprogramming into iPSCs using episomal-based plasmids without pathway perturbations. Transcriptome analysis revealed expression of a plethora of nephrogenesis-related genes such as SIX2, OSR1, CITED1, NPHS2, NPHS1, PAX2, SALL1, AQP2, EYA1, SLC12A1 and UMOD. As expected, the cells transport Albumin by endocytosis. Based on this, we refer to these cells as urine derived renal progenitor cells-UdRPCs. Associated GO-term analysis of UdRPCs and UdRPC-iPSCs underlined their renal identity and functionality. Upon differentiation by WNT activation using the GSK3β-inhibitor (CHIR99021), transcriptome and KEGG pathway analysis revealed upregulation of WNT-associated genes-AXIN2, JUN and NKD1. Protein interaction network identified JUN-a downstream target of the WNT pathway in association with STAT3, ATF2 and MAPK1 as a putative regulator of self-renewal and differentiation in UdRPCs. Furthermore, like pluripotent stem cells, self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3 pathway.Conclusion This in vitro model and the data presented should lay the foundation for studying nephrogenesis in man.

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Section: Introductionmentioning

confidence: 99%

A Comprehensive Molecular Portrait of Human Urine-derived Renal Progenitor Cells

Rahman

Wruck

Spitzhorn

et al. 2019

Preprint

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Spheroids, organoids and kidneys-on-chips: how complex human cellular models have assisted in the study of kidney disease and renal ciliopathies

Dewhurst

Molinari

Sayer

2023

Microfluid Nanofluid

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Kidney disease is one of the leading causes of morbidity worldwide, emphasizing the importance for physiologically accurate disease models. With most of the approved renal drugs failing to perform as well in human clinical trials as they did in animal testing, it is imperative that new and improved human-based models are developed to test these potential therapeutics. One option is to use patient derived cell lines, grown in both two-dimensional (2D) and three-dimensional (3D) structures, known as spheroids and organoids. Despite their contributions to the field, the lack of physiological accuracy, including the absence of fluid flow, and mechanistic effects in these 2D and 3D models means there is still room for improvement. Organ-on-a-chip (OOAC) technology offers itself as a potential candidate model to overcome these limitations. Over recent years OOAC technology has grown in popularity, with multiple organ systems, including lung, liver, and kidney described in the literature. In this review, traditional human cellular based models, including monolayer, spheroid and organoid models will be discussed. Human kidney-on-a-chip models will also be discussed, while exploring the advantages and potential limitations of this rapidly emerging field for the study of human kidney disease and drug testing.

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Ureteric bud structures generated from human iPSCs

Ryosaka

Mae

Osafune

2021

iPSCs in Tissue Engineering

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Generating Multiple Kidney Progenitors and Cell Types from Human Pluripotent Stem Cells

Cited by 6 publications

References 6 publications

A Comprehensive Molecular Portrait of Human Urine-derived Renal Progenitor Cells

A Comprehensive Molecular Portrait of Human Urine-derived Renal Progenitor Cells

Spheroids, organoids and kidneys-on-chips: how complex human cellular models have assisted in the study of kidney disease and renal ciliopathies

Ureteric bud structures generated from human iPSCs

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