{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:00:03Z","timestamp":1786132803140,"version":"build-2736575974"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R026483\/1"],"award-info":[{"award-number":["MR\/R026483\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["RP_002_20160223"],"award-info":[{"award-number":["RP_002_20160223"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["ST_001_20161116"],"award-info":[{"award-number":["ST_001_20161116"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012819","name":"Egyptian Cultural and Educational Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2020,10]]},"abstract":"\n Significance Statement<\/jats:title>\n \n There is intense interest in engineering new kidneys from embryonic stem cells and induced pluripotent stem cells as research models, and perhaps eventually for clinical transplant. Although protocols exist for producing renal organoids from stem cells, these organoids lack an essential component, the ureter. The authors describe the production of ureter-like tissue consisting of embryonic stem cell\u2013derived ureteric buds that organize\n ex fetu<\/jats:italic>\n mesenchyme around it to form smooth muscle layers. These muscles spontaneously contract with a periodicity that is a little slower than that of peristalsis in natural ureters. This work represents a step toward developing organoids with a ureter, although inducing the tissue to elongate into a tube and connect it to the kidney is a remaining challenge.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n There 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We 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\n ex fetu<\/jats:italic>\n mouse kidney rudiments.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Engineered 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\n ex fetu<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Mouse 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2019101075","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T16:15:12Z","timestamp":1598026512000},"page":"2253-2262","source":"Crossref","is-referenced-by-count":23,"title":["Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell\u2013Derived Ureteric Bud and Ex Fetu Mesenchyme"],"prefix":"10.1681","volume":"31","author":[{"given":"May","family":"Sallam","sequence":"first","affiliation":[{"name":"Deanery of Biomedical Science, University of Edinburgh, Edinburgh, UK"},{"name":"Human Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar A.","family":"Palakkan","sequence":"additional","affiliation":[{"name":"Deanery of Biomedical Science, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-6844","authenticated-orcid":false,"given":"Christopher G.","family":"Mills","sequence":"additional","affiliation":[{"name":"Deanery of Biomedical Science, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Tarnick","sequence":"additional","affiliation":[{"name":"Deanery of Biomedical Science, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Elhendawi","sequence":"additional","affiliation":[{"name":"Deanery of Biomedical Science, University of Edinburgh, Edinburgh, UK"},{"name":"Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Marson","sequence":"additional","affiliation":[{"name":"Edinburgh Transplant Centre, Royal Infirmary 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