H. pylori May Increase Risk of Stomach Cancer By Turning On Subset of Stem Cells

MedicalResearch.com Interview with:
Michael Sigal PhD

Clinical scientist of the Charité — Universitätsmedizin Berlin
Investigator at the Max Planck Institute for Infection Biology 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted to characterize the mechanisms that control the gland turnover in the stomach.

We found that Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and the other one Lgr5-negative. Both populations are affected by Rspondin 3, that is produced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling and knockout of Rspondin 3 in myofibroblasts results in loss of Lgr5 and Axin2 expression. Once we increased the bioavailability of Rspondin, that now could also interact with cells outside of the stem cell compartment, we noticed that the number of Axin2 positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced.

Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infection increases the risk for gastric cancer.

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Pancreatic Stem Cells May Reverse Diabetes and Obesity

Timothy J. Kieffer Ph.D. | Professor Laboratory of Molecular & Cellular Medicine Department of Cellular & Physiological Sciences Department of Surgery | Life Sciences Institute The University of British Columbia Vancouver BC Canada MedicalResearch.com Interview with:
Timothy J. Kieffer
 Ph.D. | Professor
Laboratory of Molecular & Cellular Medicine
Department of Cellular & Physiological Sciences
Department of Surgery | Life Sciences Institute
The University of British Columbia
Vancouver BC Canada

Medical Research: What is the background for this study? What are the main findings?

Dr. Kieffer: Previously we have examined the therapeutic potential of pancreatic precursor cells derived from human stem cells for insulin replacement in models of type 1 diabetes (PMID: 22740171 & PMID: 23771205). Here we sought to test the efficacy of cell-based insulin replacement in a model of type 2 diabetes, which is by far the most common form of diabetes. Key aspects of type 2 diabetes could be mimicked in immunodeficient mice, namely hyperglycemia and insulin resistance accompanied by excess body weight, by placing the mice on high fat diets. These diabetic mice were transplanted with human stem cell derived pancreatic precursor cells contained within macroencapsulation devices. The diabetic setting did not negatively impact the ability of the transplanted cells to mature into insulin-producing cells. Moreover, the cell transplants were able to significantly improve glucose homeostasis, particularly when combined with low doses of traditional anti-diabetic drugs. Intriguingly, the combined therapy also induced weight loss, such that treated mice were similar in weight to control mice reared on a low fat diet. Continue reading

Systemic Sclerosis: Autologous Hematopoietic Stem Cell Transplantation vs IV Pulse Cyclophosphamide

MedicalResearch.com Interview with:
ProfProf. Dr. Jacob M. van Laar Professor and Chair Dept of Rheumatology & Clinical Immunology University Medical Center Utrecht . Dr. Jacob M. van Laar
Professor and Chair
Dept of Rheumatology & Clinical Immunology
University Medical Center Utrecht

MedicalResearch: What are the main findings of the study?

Prof. van Laar: The results of the ASTIS-trial demonstrate that stem cell transplantation in selected patients with early, diffuse cutaneous systemic sclerosis, a rare, autoimmune connective tissue disease, prolongs long-term survival and improves clinical manifestations (skin, lung) and quality of life, when compared to monthly infusions with cyclophosphamide. The benefits must be weighed against the risks which include early  treatment-related mortality (10% in the ASTIS-trial) and viral infections.

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