ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery.Journal of pineal research · 2022Review
- Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine.Frontiers in cell and developmental biology · 2020Review
- Genetic ablation of carbonic anhydrase IX disrupts gastric barrier function via claudin-18 downregulation and acid backflux.Acta physiologica (Oxford, England) · 2018Article
- Article
- Multiscale positive feedbacks contribute to unidirectional gastric disease progression induced by helicobacter pylori infection.BMC systems biology · 2017Article
- Mesenchymal stromal cells' role in tumor microenvironment: involvement of signaling pathways.Cancer biology & medicine · 2017Article
- Hedgehog Signaling Links Chronic Inflammation to Gastric Cancer Precursor Lesions.Cellular and molecular gastroenterology and hepatology · 2017Review
- Hedgehog signaling in the stomach.Current opinion in pharmacology · 2016Review
- Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Hepatocytes In Vitro and In Vivo.BioMed research international · 2016Article
- Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.Advances in experimental medicine and biology · 2016Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) sustain cancer cells by creating a microenvironment favorable for tumor growth. In particular, MSCs have been implicated in gastric cancer development. There is extensive evidence suggesting that Hedgehog signaling regulates tumor growth. However, very little is known regarding the precise roles of Hedgehog signaling and MSCs in tumor development within the stomach. The current study tests that hypothesis that Sonic Hedgehog (Shh), secreted from MSCs, provides a proliferative stimulus for the gastric epithelium in the presence of inflammation. Red fluorescent protein-expressing MSCs transformed in vitro (stMSCs) were transduced with lentiviral constructs containing a vector control (stMSC(vect)) or short hairpin RNA (shRNA) targeting the Shh gene (stMSC(ShhKO)). Gastric submucosal transplantation of wild-type MSCs (wtMSCs), wild-type MSCs overexpressing Shh (wtMSC(Shh)), stMSC(vect), or stMSC(ShhKO) cells in C57BL/6 control (BL/6) or gastrin-deficient (GKO) mice was performed and mice analyzed 30 and 60 days posttransplantation. Compared with BL/6 mice transplanted with wtMSC(Shh) and stMSC(vect) cells, inflamed GKO mice developed aggressive gastric tumors. Tumor development was not observed in mouse stomachs transplanted with wtMSC or stMSC(ShhKO) cells. Compared with stMSC(ShhKO)-transplanted mice, within the inflamed GKO mouse stomach, Shh-expressing stMSC(vect)- and wtMSC(Shh)-induced proliferation of CD44-positive cells. CD44-positive cells clustered in gland-like structures within the tumor stroma and were positive for Patched (Ptch) expression. We conclude that Shh, secreted from MSCs, provides a proliferative stimulus for the gastric epithelium that is associated with tumor development, a response that is sustained by chronic inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.