Generation of human induced pluripotent stem cells from urinary cells of a healthy donor using a non-integration system

Uhm, Kyung-Ok; Jo, Eun Hee; Go, Gue Youn; Kim, Sojung; Choi, Hye Young; Im, Young Sam; Ha, Hye-Yeong; Jung, Ji‐Won; Koo, Soo Kyung

doi:10.1016/j.scr.2017.03.019

Cited by 12 publications

(7 citation statements)

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“…Expression of pluripotency-associated proteins has enabled rapid reprogramming of urine derived mesenchymal and epithelial cells into induced pluripotent stem cells (iPSCs) [37][38][39][40][41] . Differentiation protocols for generating kidney-associated cell types from human pluripotent stem cells have mimicked normal kidney development 28,[42][43][44] .…”

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confidence: 99%

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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confidence: 99%

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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“…Another widely used method for iPSC reprogramming is Sendai virus, which is a single stranded negative sense RNA virus that does not integrate into the genome. Sendai reprogramming has been used to generate UiPSCs from the urine of patients with attention deficit hyperactivity disorder (ADHD) [ 67 ], obsessive–compulsive disorder [ 68 ], Duchenne muscular dystrophy [ 69 – 71 ], dilated cardiomyopathy [ 72 ], heterozygous PAI-I mutation [ 73 ], ventricular septal defect (VSD) [ 74 ], X-linked Alport syndrome (X-LAS) [ 75 ], spinal cord injury [ 76 ], type 2 diabetes mellitus [ 77 ], and healthy donors [ 78 ]. The majority of the iPSC colonies were undetectable for Sendai virus transgenes after 7 passages [ 67 ].…”

Section: Generation Of Ipscs and Inscs From Uscsmentioning

confidence: 99%

Urine-derived induced pluripotent/neural stem cells for modeling neurological diseases

Shi

Cheung

2021

Cell Biosci

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Neurological diseases are mainly modeled using rodents through gene editing, surgery or injury approaches. However, differences between humans and rodents in terms of genetics, neural development, and physiology pose limitations on studying disease pathogenesis in rodent models for neuroscience research. In the past decade, the generation of induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) by reprogramming somatic cells offers a powerful alternative for modeling neurological diseases and for testing regenerative medicines. Among the different somatic cell types, urine-derived stem cells (USCs) are an ideal cell source for iPSC and iNSC reprogramming, as USCs are highly proliferative, multipotent, epithelial in nature, and easier to reprogram than skin fibroblasts. In addition, the use of USCs represents a simple, low-cost and non-invasive procedure for generating iPSCs/iNSCs. This review describes the cellular and molecular properties of USCs, their differentiation potency, different reprogramming methods for the generation of iPSCs/iNSCs, and their potential applications in modeling neurological diseases.

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“…By contrast, urine contains several types of somatic cells [ 6 ], such as squamous epithelial cells from the urethra and bladder and renal tubular cells, which can be cultured after collection. Induced pluripotent stem (iPS) cells have been established from human urine-derived cells [ 7 8 9 10 ], suggesting that urine-derived cells are a good candidate donor for NT [ 11 ]. In addition, the successful cloning of cattle and mice by urine-derived cells has improved confidence in the cloning of pigs from this type of cell.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of porcine urine-derived cells as nuclei donor for somatic cell nuclear transfer

et al. 2022

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Background Somatic cell nuclear transfer (SCNT) is used widely in cloning, stem cell research, and regenerative medicine. The type of donor cells is a key factor affecting the SCNT efficiency. Objectives This study examined whether urine-derived somatic cells could be used as donors for SCNT in pigs. Methods The viability of cells isolated from urine was assessed using trypan blue and propidium iodide staining. The H3K9me3/H3K27me3 level of the cells was analyzed by immunofluorescence. The in vitro developmental ability of SCNT embryos was evaluated by the blastocyst rate and the expression levels of the core pluripotency factor. Blastocyst cell apoptosis was examined using a terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. The in vivo developmental ability of SCNT embryos was evaluated after embryo transfer. Results Most sow urine-derived cells were viable and could be cultured and propagated easily. On the other hand, most of the somatic cells isolated from the boar urine exhibited poor cellular activity. The in vitro development efficiency between the embryos produced by SCNT using porcine embryonic fibroblasts (PEFs) and urine-derived cells were similar. Moreover, The H3K9me3 in SCNT embryos produced from sow urine-derived cells and PEFs at the four-cell stage showed similar intensity. The levels of Oct4, Nanog, and Sox2 expression in blastocysts were similar in the two groups. Furthermore, there is a similar apoptotic level of cloned embryos produced by the two types of cells. Finally, the full-term development ability of the cloned embryos was evaluated, and the cloned fetuses from the urine-derived cells showed absorption. Conclusions Sow urine-derived cells could be used to produce SCNT embryos.

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Generation of human induced pluripotent stem cells from urinary cells of a healthy donor using a non-integration system

Cited by 12 publications

References 2 publications

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

Urine-derived induced pluripotent/neural stem cells for modeling neurological diseases

Evaluation of porcine urine-derived cells as nuclei donor for somatic cell nuclear transfer

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