Skip to main content
Erschienen in: Pediatric Surgery International 1/2023

01.12.2023 | Original Article

Successful engraftment of bladder organoids in de-epithelialized mouse colon

verfasst von: Kazuto Suda, Yuka Matsumoto, Takanori Ochi, Hiroyuki Koga, Geoffrey J. Lane, Nobutaka Hattori, Tetsuya Nakamura, Atsuyuki Yamataka

Erschienen in: Pediatric Surgery International | Ausgabe 1/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To engraft bladder organoids (BO) on de-epithelialized mouse colon using an epithelial replacement technique.

Methods

BO cultured using bladder specimens from enhanced green fluorescent protein (EGFP) transgenic mice were engrafted to replace proximal colon epithelium stripped from an approximately 1 cm long target site in syngeneic wild-type recipient mice (n = 9) by exposure to ethylenediaminetetraacetic acid by infusion and flushing with phosphate buffered saline. Target sites were harvested on postoperative days 2, 7, and 28 for hematoxylin–eosin staining and immunofluorescence.

Results

Histology on postoperative days 7 and 28 showed BO derived EGFP + cells forming multiple layers on the luminal surface of the colon. Immunohistochemistry showed that EGFP + areas were positive for CK5 and CK14, markers for basal and immature subtype urothelium, respectively, but negative for CA2, a marker for colonic epithelium. Ki67 was detected predominantly in the basal parts of EGFP + areas on postoperative day 7 and day 28.

Conclusions

This is the first report of successful engraftment of BO in de-epithelialized colon with urothelial tissue reconstituted by actively proliferating cells. This technique could be developed for augmentation cystoplasty to prevent bladder calculi formation and malignant transformation.
Literatur
2.
Zurück zum Zitat Kispal ZF, Kardos D, Jilling T, Kereskai L, Isaacs M, Balogh DL et al (2015) Long-term histological and mucin alterations in the neobladder mucosa following urinary bladder augmentation or substitution with gastrointestinal segment. J Pediatr Urol 11(6):349.e1–6CrossRefPubMed Kispal ZF, Kardos D, Jilling T, Kereskai L, Isaacs M, Balogh DL et al (2015) Long-term histological and mucin alterations in the neobladder mucosa following urinary bladder augmentation or substitution with gastrointestinal segment. J Pediatr Urol 11(6):349.e1–6CrossRefPubMed
3.
Zurück zum Zitat Hayashi Y, Nishimura E, Shimizu S, Miyano G, Okawada M, Nagae I et al (2017) Sigmoidocolocystoplasty for neurogenic bladder reviewed after 20 years. J Pediatr Surg 52(12):2070–2073CrossRefPubMed Hayashi Y, Nishimura E, Shimizu S, Miyano G, Okawada M, Nagae I et al (2017) Sigmoidocolocystoplasty for neurogenic bladder reviewed after 20 years. J Pediatr Surg 52(12):2070–2073CrossRefPubMed
4.
Zurück zum Zitat Peycelon M, Szymanski KM, Francesca Monn M, Salama AK, Risk H, Cain MP et al (2020) Adherence with bladder irrigation following augmentation. J Pediatr Urol 16(1):33.e1-e8CrossRef Peycelon M, Szymanski KM, Francesca Monn M, Salama AK, Risk H, Cain MP et al (2020) Adherence with bladder irrigation following augmentation. J Pediatr Urol 16(1):33.e1-e8CrossRef
5.
Zurück zum Zitat Kitamura K, Isotani S, Muto S, Horie S (2022) Efficacy of pembrolizumab in a rare type of bladder cancer arising 25 years after augmentation cystoplasty. BMJ Case Rep 15(3) Kitamura K, Isotani S, Muto S, Horie S (2022) Efficacy of pembrolizumab in a rare type of bladder cancer arising 25 years after augmentation cystoplasty. BMJ Case Rep 15(3)
6.
Zurück zum Zitat Hayashi Y, Shiyanagi S, Okawada M, Koga H, Fujimura J, Nagae I et al (2015) Undifferentiated sarcoma developing 14 years after colocystoplasty: our experience and literature review. J Ped Surg Case Rep 3:385–388 Hayashi Y, Shiyanagi S, Okawada M, Koga H, Fujimura J, Nagae I et al (2015) Undifferentiated sarcoma developing 14 years after colocystoplasty: our experience and literature review. J Ped Surg Case Rep 3:385–388
7.
Zurück zum Zitat Tekgül S, Oge O, Bal K, Erkan I, Bakkaloğlu M (2000) Ureterocystoplasty: an alternative reconstructive procedure to enterocystoplasty in suitable cases. J Pediatr Surg 35(4):577–579CrossRefPubMed Tekgül S, Oge O, Bal K, Erkan I, Bakkaloğlu M (2000) Ureterocystoplasty: an alternative reconstructive procedure to enterocystoplasty in suitable cases. J Pediatr Surg 35(4):577–579CrossRefPubMed
8.
Zurück zum Zitat Clevers H, Conder RK, Li VSW, Lutolf MP, Vallier L, Chan S et al (2019) Tissue-engineering the intestine: the trials before the trials. Cell Stem Cell 24(6):855–859CrossRefPubMed Clevers H, Conder RK, Li VSW, Lutolf MP, Vallier L, Chan S et al (2019) Tissue-engineering the intestine: the trials before the trials. Cell Stem Cell 24(6):855–859CrossRefPubMed
9.
Zurück zum Zitat Sugimoto S, Kobayashi E, Fujii M, Ohta Y, Arai K, Matano M et al (2021) An organoid-based organ-repurposing approach to treat short bowel syndrome. Nature 592(7852):99–104PubMed Sugimoto S, Kobayashi E, Fujii M, Ohta Y, Arai K, Matano M et al (2021) An organoid-based organ-repurposing approach to treat short bowel syndrome. Nature 592(7852):99–104PubMed
10.
Zurück zum Zitat Mullenders J, de Jongh E, Brousali A, Roosen M, Blom JPA, Begthel H et al (2019) Mouse and human urothelial cancer organoids: a tool for bladder cancer research. Proc Natl Acad Sci USA 116(10):4567–4574CrossRefPubMedPubMedCentral Mullenders J, de Jongh E, Brousali A, Roosen M, Blom JPA, Begthel H et al (2019) Mouse and human urothelial cancer organoids: a tool for bladder cancer research. Proc Natl Acad Sci USA 116(10):4567–4574CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Date S, Sato T (2015) Mini-gut organoids: reconstitution of the stem cell niche. Annu Rev Cell Dev Biol 31:269–289CrossRefPubMed Date S, Sato T (2015) Mini-gut organoids: reconstitution of the stem cell niche. Annu Rev Cell Dev Biol 31:269–289CrossRefPubMed
12.
Zurück zum Zitat Nakamura T, Sato T (2018) Advancing intestinal organoid technology toward regenerative medicine. Cell Mol Gastroenterol Hepatol 5(1):51–60CrossRefPubMed Nakamura T, Sato T (2018) Advancing intestinal organoid technology toward regenerative medicine. Cell Mol Gastroenterol Hepatol 5(1):51–60CrossRefPubMed
13.
Zurück zum Zitat Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X et al (2012) Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nat Med 18(4):618–623CrossRefPubMed Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X et al (2012) Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nat Med 18(4):618–623CrossRefPubMed
14.
Zurück zum Zitat Okabe M, Ikawa M, Kominami K, Nakanishi T, Nishimune Y (1997) “Green mice” as a source of ubiquitous green cells. FEBS Lett 407(3):313–319CrossRefPubMed Okabe M, Ikawa M, Kominami K, Nakanishi T, Nishimune Y (1997) “Green mice” as a source of ubiquitous green cells. FEBS Lett 407(3):313–319CrossRefPubMed
15.
Zurück zum Zitat Fukuda M, Mizutani T, Mochizuki W, Matsumoto T, Nozaki K, Sakamaki Y et al (2014) Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. Genes Dev 28(16):1752–1757CrossRefPubMedPubMedCentral Fukuda M, Mizutani T, Mochizuki W, Matsumoto T, Nozaki K, Sakamaki Y et al (2014) Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. Genes Dev 28(16):1752–1757CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Papafotiou G, Paraskevopoulou V, Vasilaki E, Kanaki Z, Paschalidis N, Klinakis A (2016) KRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis. Nat Commun 7:11914CrossRefPubMedPubMedCentral Papafotiou G, Paraskevopoulou V, Vasilaki E, Kanaki Z, Paschalidis N, Klinakis A (2016) KRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis. Nat Commun 7:11914CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Abelson B, Sun D, Que L, Nebel RA, Baker D, Popiel P et al (2018) Sex differences in lower urinary tract biology and physiology. Biol Sex Differ 9(1):45CrossRefPubMedPubMedCentral Abelson B, Sun D, Que L, Nebel RA, Baker D, Popiel P et al (2018) Sex differences in lower urinary tract biology and physiology. Biol Sex Differ 9(1):45CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Sun W, Wilhelmina Aalders T, Oosterwijk E (2014) Identification of potential bladder progenitor cells in the trigone. Dev Biol 393(1):84–92CrossRefPubMed Sun W, Wilhelmina Aalders T, Oosterwijk E (2014) Identification of potential bladder progenitor cells in the trigone. Dev Biol 393(1):84–92CrossRefPubMed
19.
20.
Zurück zum Zitat Park JH, Kotani T, Konno T, Setiawan J, Kitamura Y, Imada S et al (2016) Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids. PLoS ONE 11(5):e0156334CrossRefPubMedPubMedCentral Park JH, Kotani T, Konno T, Setiawan J, Kitamura Y, Imada S et al (2016) Promotion of intestinal epithelial cell turnover by commensal bacteria: role of short-chain fatty acids. PLoS ONE 11(5):e0156334CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Majewski T, Lee S, Jeong J, Yoon DS, Kram A, Kim MS et al (2008) Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy. Lab Invest 88(7):694–721CrossRefPubMedPubMedCentral Majewski T, Lee S, Jeong J, Yoon DS, Kram A, Kim MS et al (2008) Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy. Lab Invest 88(7):694–721CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Shin K, Lee J, Guo N, Kim J, Lim A, Qu L et al (2011) Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472(7341):110–114CrossRefPubMedPubMedCentral Shin K, Lee J, Guo N, Kim J, Lim A, Qu L et al (2011) Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472(7341):110–114CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Volkmer JP, Sahoo D, Chin RK, Ho PL, Tang C, Kurtova AV et al (2012) Three differentiation states risk-stratify bladder cancer into distinct subtypes. Proc Natl Acad Sci USA 109(6):2078–2083CrossRefPubMedPubMedCentral Volkmer JP, Sahoo D, Chin RK, Ho PL, Tang C, Kurtova AV et al (2012) Three differentiation states risk-stratify bladder cancer into distinct subtypes. Proc Natl Acad Sci USA 109(6):2078–2083CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Yamataka A, Wang K, Kato Y, Okada Y, Kobayashi H, Lane GJ et al (2005) Long-term outcome of bladder augmentation using living-related partial bladder transplantation in rats. Pediatr Res 57(5 Pt 1):738–743CrossRefPubMed Yamataka A, Wang K, Kato Y, Okada Y, Kobayashi H, Lane GJ et al (2005) Long-term outcome of bladder augmentation using living-related partial bladder transplantation in rats. Pediatr Res 57(5 Pt 1):738–743CrossRefPubMed
25.
Zurück zum Zitat Kajbafzadeh AM, Khorramirouz R, Sabetkish S, Ataei Talebi M, Akbarzadeh A, Keihani S (2016) In vivo regeneration of bladder muscular wall using decellularized colon matrix: an experimental study. Pediatr Surg Int 32(6):615–622CrossRefPubMed Kajbafzadeh AM, Khorramirouz R, Sabetkish S, Ataei Talebi M, Akbarzadeh A, Keihani S (2016) In vivo regeneration of bladder muscular wall using decellularized colon matrix: an experimental study. Pediatr Surg Int 32(6):615–622CrossRefPubMed
Metadaten
Titel
Successful engraftment of bladder organoids in de-epithelialized mouse colon
verfasst von
Kazuto Suda
Yuka Matsumoto
Takanori Ochi
Hiroyuki Koga
Geoffrey J. Lane
Nobutaka Hattori
Tetsuya Nakamura
Atsuyuki Yamataka
Publikationsdatum
01.12.2023
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Surgery International / Ausgabe 1/2023
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-022-05294-w

Weitere Artikel der Ausgabe 1/2023

Pediatric Surgery International 1/2023 Zur Ausgabe

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

23.04.2024 Typ-1-Diabetes Nachrichten

Wenn Kinder an Werktagen zum Arzt gehen, werden neu auftretender Typ-1-Diabetes und diabetische Ketoazidosen häufiger erkannt als bei Arztbesuchen an Wochenenden oder Feiertagen.

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

22.04.2024 Fehlsichtigkeit Nachrichten

Augentropfen mit niedrig dosiertem Atropin können helfen, das Fortschreiten einer Kurzsichtigkeit bei Kindern zumindest zu verlangsamen, wie die Ergebnisse einer aktuellen Studie mit verschiedenen Dosierungen zeigen.

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

18.04.2024 Spinale Muskelatrophien Nachrichten

Seit 2021 ist die Untersuchung auf spinale Muskelatrophie Teil des Neugeborenen-Screenings in Deutschland. Eine Studie liefert weitere Evidenz für den Nutzen der Maßnahme.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.