R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.

Lugli, Natalia; Kamileri, Irene; Keogh, Adrian; Malinka, Thomas; Sarris, Michalis E; Talianidis, Iannis; Schaad, Olivier; Candinas, Daniel; Halazonetis, Thanos D; Keogh-Stroka, Deborah M. (2016). R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders. EMBO reports, 17(5), pp. 769-779. Nature Publishing Group 10.15252/embr.201642169

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Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine, and colon. Expansion of these cells requires activation of the receptor Lgr5 by its ligand R-spondin 1 and is likely facilitated by the fact that in healthy adults the stem cells in these organs are highly proliferative. In many other adult organs, such as the liver, proliferating cells are normally not abundant in adulthood. However, upon injury, the liver has a strong regenerative potential that is accompanied by the emergence of Lgr5-positive stem cells; these cells can be isolated and expanded in vitro as organoids. In an effort to isolate stem cells from non-regenerating mouse livers, we discovered that healthy gallbladders are a rich source of stem/progenitor cells that can be propagated in culture as organoids for more than a year. Growth of these organoids was stimulated by R-spondin 1 and noggin, whereas in the absence of these growth factors, the organoids differentiated partially toward the hepatocyte fate. When transplanted under the liver capsule, gallbladder-derived organoids maintained their architecture for 2 weeks. Furthermore, single cells prepared from dissociated organoids and injected into the mesenteric vein populated the liver parenchyma of carbon tetrachloride-treated mice. Human gallbladders were also a source of organoid-forming stem cells. Thus, under specific growth conditions, stem cells can be isolated from healthy gallbladders, expanded almost indefinitely in vitro, and induced to differentiate toward the hepatocyte lineage.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Keogh, Adrian; Malinka, Thomas; Candinas, Daniel and Keogh-Stroka, Deborah M.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1469-221X

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

29 Mar 2017 15:55

Last Modified:

29 Mar 2017 15:55

Publisher DOI:

10.15252/embr.201642169

PubMed ID:

26993089

Uncontrolled Keywords:

R‐spondin 1; gallbladder; noggin; organoids; stem cells

BORIS DOI:

10.7892/boris.93391

URI:

https://boris.unibe.ch/id/eprint/93391

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