Correction to: Urine-derived cells for human cell therapy

Manaph, Nimshitha Pavathuparambil Abdul; Al‐Hawwas, Mohammed; Bobrovskaya, Larisa; Coates, Penelope; Zhou, Xin‐Fu

doi:10.1186/s13287-018-0974-2

Cited by 10 publications

(12 citation statements)

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“…Moreover, the GOs from the urine cell derived-iPSC exclusive genes-set, in contrast to pluripotent stem cells, identified terms related to renal function therefore implying the preservation of their kidney origin. As the conservation of tissue of origin in iPSCs might be linked to epigenetic memory 17,70 , urine-derived renal progenitors as well as corresponding-iPSCs, especially with known CYP2D6 status, might be advantageous for differentiation into renal cells, modelling kidney-related diseases, nephrotoxicity studies and regenerative medicine 55 .…”

Section: Discussionmentioning

confidence: 99%

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The FGF, TGFβ and WNT axis Modulate Self-renewal of Human SIX2+ Urine Derived Renal Progenitor Cells

Rahman

Wruck

Spitzhorn

et al. 2020

Sci Rep

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Human urine is a non-invasive source of renal stem cells with regeneration potential. Urine-derived renal progenitor cells were isolated from 10 individuals of both genders and distinct ages. These renal progenitors express pluripotency-associated proteins-TRA-1-60, TRA-1-81, SSEA4, C-KIT and CD133, as well as the renal stem cell markers-SIX2, CITED1, WT1, CD24 and CD106. The transcriptomes of all SIX2 + renal progenitors clustered together, and distinct from the human kidney biopsy-derived epithelial proximal cells (hRepcs). Stimulation of the urine-derived renal progenitor cells (UdRpcs) with the GSK3β-inhibitor (CHIR99021) induced differentiation. 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 negative regulator of self-renewal. furthermore, like pluripotent stem cells, self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3 pathway. The urine-derived renal progenitor cells and the data presented should lay the foundation for studying nephrogenesis in human. According to the International Society of Nephrology, more than 850 million people worldwide are afflicted with kidney diseases 1 , which raises the quest for alternative therapies to overcome the limitations associated with current treatments including transplantation and dialysis. One of the most promising options is the utilization of renal stem cells for treating of kidney diseases, disease modelling, and drug development 2,3. Renal stem/ progenitor cells are self-renewing, multipotent cells with the ability to generate various cell types of the kidney to maintain renal function 4. These progenitors are in abundance during fetal kidney development in which the renal progenitor surface marker CD24 and stem cell self-renewal marker CD133 cells are required for primordial nephrogenesis 5,6. However, in adults, CD24, CD133 (Prominin-1) and vascular cell adhesion molecule 1 (CD106)-positive renal progenitors are present in renal tubules and capsules 7. Two progenitor cell populations can be distinguished based on the expression of CD106. For instance, CD24 + CD133 + CD106 − progenitors are present in proximal tubules whereas CD24 + CD133 + CD106 + cells are localized in the Bowman's capsule. The latter can differentiate into a variety of cell types of renal tissue such as podocytes and tubular epithelial cells 4-7. Several groups have identified urine as a non-invasive and repetitive source of renal progenitor cells 8,9. It has been estimated that each day approximately 2,000 to 7,000 cells composed of differentiated epithelial cells, bi-potential epithelial cells (transitional cells), multipotent mesenchymal stem cells, and glomerular parietal cells are flushed out from the renal tubular network and the upper urinary tract into urine 10-12. A subpopulation of these urine-derived cells are renal stem/progenitor cells which express master renal markers such as Sine...

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Section: Discussionmentioning

confidence: 99%

“…Vimentin, CD105, CD90, CD73 and not the hematopoietic stem cell markers-CD14, CD31, CD34 and CD45 17,18 . Although, research interest on urine derived renal stem cells is gradually increasing but the mechanistic role of genetic factors in these cells in vitro regarding progenitor/differentiated status maintenance is not clear.…”

mentioning

confidence: 93%

The FGF, TGFβ and WNT axis Modulate Self-renewal of Human SIX2+ Urine Derived Renal Progenitor Cells

Rahman

Wruck

Spitzhorn

et al. 2020

Sci Rep

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“…Furthermore, the GOs from the UdRPCs-iPSC exclusive genes set, in contrast to pluripotent stem cells, identified terms related to renal function therefore implying the preservation of their kidney origin ( Figure 4E). As the conservation of tissue of origin in iPSCs might be linked to epigenetic memory, 4,64 UdRPCs as well as UdRPCs-iPSCs, especially with known CYP2D6 status, might be advantageous for differentiation into renal cells, modelling kidney-related diseases, nephrotoxicity studies and regenerative medicine. However, dissecting the gene regulatory mechanisms that drive human renal progenitor growth and differentiation in vitro represents the key step for translation but remains a challenge due to the absence of well-characterised urine derived stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…Further, they endow multi-differentiation potential and like bone marrow derived mesenchymal stem cells express Vimentin, CD105, CD90, CD73 and not the hematopoietic stem cell markers-CD14, CD31, CD34 and CD45. 4,5 Studies in mice have shown that Osr1, Six2, Wnt and Wt1 are required to maintain renal progenitor cells during kidney organogenesis. 6,7,8,9,10,11 Additionally, signalling pathways such as Wnt, Fgf, Tgfβ and Notch play major roles in renal stem cell maintenance and differentiation.…”

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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“…Upon in vitro culture, the undifferentiated cells, which include renal cells and the adult stem cells, and urine stem cells (USCs), expand to yield patient-specific urine-derived cells (UDCs). 16 Although USCs are only 0.2%, they are the most significant cells in urine since they are the most expandable ones and have been isolated from diseased patients' urine including DMD unlike renal cells, which have only been isolated from healthy individuals. [16][17][18] Just 100 mL of urine yields ~2-10 USCs, which replicate to ~0.5-1 million after just 10-15 days of culturing.…”

mentioning

confidence: 99%

Induced pluripotent stem cells from urine of Duchenne muscular dystrophy patients

Ghori

Wahid

2021

Pediatrics International

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Background The most common muscular dystrophy, Duchenne muscular dystrophy (DMD), is a lethal, X‐linked disorder with no widespread cure. Worldwide, in vitro studies involving new, mutation‐specific cures and regenerative therapies are employing disease‐specific patient‐specific cells. However, these may not be completely relevant for Pakistani children because of the human genome diversities and geographic variation in mutation type and frequency. Therefore, this study aimed to generate DMD induced pluripotent stem cells (iPSCs) from the urine of Pakistani children with DMD, to serve as a precious source of differentiated cells, such as Pakistani DMD‐cardiomyocytes, for future disease‐modelling, drug testing, and gene therapy. Methods Urine‐derived cells (UDCs) isolated from mid‐stream urine underwent molecular characterization and cellular reprogramming towards iPSCs using the episomal vector system followed by molecular profiling of the iPSCs. Results Colonies of elongated and spindle‐shaped or rounded rice‐grain like UDCs were spotted 4–7 days after plating and expanded rapidly with a second passage at 2–3 weeks. Multicolor flow cytometry confirmed the expression of mesenchymal stem‐cell markers. The reprogramed iPSCs consisted of colonies of round, tightly‐packed cells with large nuclei that were positively fluorescent for the pluripotency markers octamer binding transcription factor‐4 (OCT‐4), tumour resistance antigen 1–60 (TRA‐1‐60), and stage specific embryonic 4 antigen (SSEA‐4), but not for the negative pluripotency marker SSEA‐1. To the best of our knowledge, this was the first time DMD‐iPSCs have been generated for Pakistani children. Conclusion This integration‐free, feeder‐free, efficient, and reproducible reprogramming method employed UDCs. Urine is a low‐cost, non‐invasive, painless, and repeatable source of rapidly expandable cells from children and morbid individuals for obtaining autologous cells for drug‐assays and disease‐modelling, suitable for DMD and other debilitating diseases.

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Correction to: Urine-derived cells for human cell therapy

Cited by 10 publications

References 1 publication

The FGF, TGFβ and WNT axis Modulate Self-renewal of Human SIX2+ Urine Derived Renal Progenitor Cells

The FGF, TGFβ and WNT axis Modulate Self-renewal of Human SIX2+ Urine Derived Renal Progenitor Cells

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

Induced pluripotent stem cells from urine of Duchenne muscular dystrophy patients

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