Engineered kidneys: principles, progress, and prospects

Davies, Jamie A.; Chang, C‐Hong; Lawrence, Melanie L.; Mills, Christopher G.; Mullins, John J.

doi:10.3402/arb.v1.24990

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…It is now possible to produce renal organoids, representing immature kidneys and showing some physiological functions, from embryonic and induced pluripotent cells of mouse and human. [1][2][3][4][5][6] So far, these organoids have not featured a ureter. This report describes a technique for differentiating mouse ES cells into urothelium that can organize fetal peri-Wolffian mesenchyme around it to produce contractile muscle layers.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell–Derived Ureteric Bud and Ex Fetu Mesenchyme

Sallam

Palakkan

Mills

et al. 2020

JASN

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BackgroundThere is intense interest in replacing kidneys from stem cells. It is now possible to produce, from embryonic or induced pluripotent stem cells, kidney organoids that represent immature kidneys and display some physiologic functions. However, current techniques have not yet resulted in renal tissue with a ureter, which would be needed for engineered kidneys to be clinically useful.MethodsWe used a published sequence of growth factors and drugs to induce mouse embryonic stem cells to differentiate into ureteric bud tissue. We characterized isolated engineered ureteric buds differentiated from embryonic stem cells in three-dimensional culture and grafted them into ex fetu mouse kidney rudiments.ResultsEngineered ureteric buds branched in three-dimensional culture and expressed Hoxb7, a transcription factor that is part of a developmental regulatory system and a ureteric bud marker. When grafted into the cortex of ex fetu kidney rudiments, engineered ureteric buds branched and induced nephron formation; when grafted into peri-Wolffian mesenchyme, still attached to a kidney rudiment or in isolation, they did not branch but instead differentiated into multilayer ureter-like epithelia displaying robust expression of the urothelial marker uroplakin. This engineered ureteric bud tissue also organized the mesenchyme into smooth muscle that spontaneously contracted, with a period a little slower than that of natural ureteric peristalsis.ConclusionsMouse embryonic stem cells can be differentiated into ureteric bud cells. Grafting those UB-like structures into peri-Wolffian mesenchyme of cultured kidney rudiments can induce production of urothelium and organize the mesenchyme to produce rhythmically contracting smooth muscle layers. This development may represent a significant step toward the goal of renal regeneration.

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Section: Introductionmentioning

confidence: 99%

Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell–Derived Ureteric Bud and Ex Fetu Mesenchyme

Sallam

Palakkan

Mills

et al. 2020

JASN

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“…Furthermore, DIRECT demonstrated the cardio-metabolic benefit of metformin (178), BEAT-DKD supported the clinical efficacy of SGLT2 inhibitors and GLP1R agonists in diabetic patients with DKD (179,180), and StemBANCC established four different stem cell-based replacement treatments (181)(182)(183). For large-scale production, StemBANCC demonstrated that the continuous peristaltic pump-based circulation technology, in a hydraulically driven bioreactor, can be a potential 3D tool and a key in this process (184).…”

Section: Resultsmentioning

confidence: 97%

Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative

2021

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Diabetes Mellitus is one of the World Health Organization's priority diseases under research by the first and second programmes of Innovative Medicines Initiative, with the acronyms IMI1 and IMI2, respectively. Up to October of 2019, 13 projects were funded by IMI for Diabetes & Metabolic disorders, namely SUMMIT, IMIDIA, DIRECT, StemBANCC, EMIF, EBiSC, INNODIA, RHAPSODY, BEAT-DKD, LITMUS, Hypo-RESOLVE, IM2PACT, and CARDIATEAM. In general, a total of €447 249 438 was spent by IMI in the area of Diabetes. In order to prompt a better integration of achievements between the different projects, we perform a literature review and used three data sources, namely the official project's websites, the contact with the project's coordinators and co-coordinator, and the CORDIS database. From the 662 citations identified, 185 were included. The data collected were integrated into the objectives proposed for the four IMI2 program research axes: (1) target and biomarker identification, (2) innovative clinical trials paradigms, (3) innovative medicines, and (4) patient-tailored adherence programmes. The IMI funded projects identified new biomarkers, medical and research tools, determinants of inter-individual variability, relevant pathways, clinical trial designs, clinical endpoints, therapeutic targets and concepts, pharmacologic agents, large-scale production strategies, and patient-centered predictive models for diabetes and its complications. Taking into account the scientific data produced, we provided a joint vision with strategies for integrating personalized medicine into healthcare practice. The major limitations of this article were the large gap of data in the libraries on the official project websites and even the Cordis database was not complete and up to date.

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“…Grown from stem cells from a mouse embryo, it is only 3 mm across. It was made by experimental anatomist Jamie A. Davies and renal biochemist Melanie Lawrence at the University of Edinburgh Integrative Physiology Laboratory in 2015 (Davies et al 2014), with the potential to support pharmacological research. The investigators -to whom we were introduced by 3D printing researchers -grew this kidney specifically for the Museum, and altered their usual techniques by using silver stain on it, which has better longer-term survival prospects.…”

Section: Organsmentioning

confidence: 99%

Collecting contemporary science, technology and medicine

Alberti

Cox

Phillipson

et al. 2018

Museum Management and Curatorship

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Museums are often associated exclusively with bygones. This can be problematic, especially for those who manage science, technology and medicine (STM) collections. In seeking to correct this misconception with contemporary collecting, they also face other problems, especially in scale and complexity. While acknowledging such challenges, this opinion piece proposes opportunities afforded by the material culture of recent STM. Contemporary material can be used to tell stories as well as explain technicalities; it can connect with visitors using everyday objects and put 'difficult' material into context.

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Engineered kidneys: principles, progress, and prospects

Cited by 7 publications

References 20 publications

Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell–Derived Ureteric Bud and Ex Fetu Mesenchyme

Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell–Derived Ureteric Bud and Ex Fetu Mesenchyme

Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative

Collecting contemporary science, technology and medicine

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