Therapeutic effects of placenta derived-, umbilical cord derived-, and adipose tissue derived-mesenchymal stem cells in chronic Helicobacter pylori infection: comparison and novel mechanisms

Supported with significant rejuvenating and regenerating actions of mesenchymal stem cells (MSCs) in various gastrointestinal diseases including Helicobacter pylori (H. pylori)-associated gastric diseases, we have compared these actions among placenta derived-MSCs (PD-MSCs), umbilical cord derived-MSCs (UC-MSCs), and adipose tissue derived-MSCs (AD-MSCs) and explored contributing genes implicated in rejuvenation of H. pylori-chronic atrophic gastritis (CAG) and tumorigenesis. In this study adopting H. pylori-initiated, high salt diet-promoted gastric carcinogenesis model, we have administered three kinds of MSCs around 15–18 weeks in H. pylori infected C57BL/6 mice and sacrificed at 24 and 48 weeks, respectively, in order to either assess the rejuvenating capability or anti-tumorigenesis. At 24 weeks, MSCs all led to significantly mitigated atrophic gastritis, for which significant inductions of autophagy, preservation of tumor suppressive 15-PGDH, attenuated apoptosis, and efficient efferocytosis was imposed with MSCs administration during atrophic gastritis. At 48 weeks, MSCs administered during H. pylori-associated atrophic gastritis afforded significant blocking the progression of CAG, as evidenced with statistically significant reduction in H. pylori-associated gastric tumor (p<0.05) accompanied with significant decreases in IL-1β, COX-2, STAT3, and NF-κB. Combined together with the changes of stanniocalcin-1 (STC-1), thrombospondin-1 (TSP-1), and IL-10 known as biomarkers reflecting stem cell activities at 48 weeks after H. pylori, PD-MSCs among MSCs afforded the best rejuvenating action against H. pylori-associated CAG via additional actions of efferocytosis, autophagy, and anti-apoptosis at 24 weeks. In conclusion, MSCs, especially PD-MSCs, exerted rejuvenating actions against H. pylori-associated CAG via anti-mutagenesis of IL-10, CD-36, ATG5 and cancer suppressive influences of STC-1, TSP-1, and 15-PGDH.

[1]  C. Loh,et al.  Human Wharton’s Jelly Mesenchymal Stem Cell-Mediated Sciatic Nerve Recovery Is Associated with the Upregulation of Regulatory T Cells , 2020, International journal of molecular sciences.

[2]  Y. Hu,et al.  Inhibition of autophagy aggravates DNA damage response and gastric tumorigenesis via Rad51 ubiquitination in response to H. pylori infection , 2020, Gut microbes.

[3]  N. Fang,et al.  Effect of peripheral blood-derived mesenchymal stem cells on macrophage polarization and Th17/Treg balance in vitro , 2020, Regenerative therapy.

[4]  Wei Liu,et al.  Mesenchymal stromal cells ameliorate acute lung injury induced by LPS mainly through stanniocalcin-2 mediating macrophage polarization , 2020, Annals of translational medicine.

[5]  Hua-ling Wang,et al.  Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro , 2020, Stem Cell Research & Therapy.

[6]  Wen-Ching Wang,et al.  Cellular evasion strategies of Helicobacter pylori in regulating its intracellular fate , 2020, Seminars in Cell & Developmental Biology.

[7]  Y. Gui,et al.  Neuroprotective Effects of Umbilical Cord-Derived Mesenchymal Stem Cells on Radiation-Induced Brain Injury in Mice. , 2020, Annals of clinical and laboratory science.

[8]  Liangzhi Wen,et al.  Autophagy and Gastrointestinal Diseases. , 2020, Advances in experimental medicine and biology.

[9]  C. Xiang,et al.  Menstrual blood-derived stem cells: toward therapeutic mechanisms, novel strategies, and future perspectives in the treatment of diseases , 2019, Stem Cell Research & Therapy.

[10]  Yumin Li,et al.  Molecular mechanism of Helicobacter pylori-induced autophagy in gastric cancer. , 2019, Oncology letters.

[11]  K. Hahm,et al.  Umbilical cord/placenta-derived mesenchymal stem cells inhibit fibrogenic activation in human intestinal myofibroblasts via inhibition of myocardin-related transcription factor A , 2019, Stem Cell Research & Therapy.

[12]  B. Yousefi,et al.  Current information on the association of Helicobacter pylori with autophagy and gastric cancer , 2019, Journal of cellular physiology.

[13]  Yutao Guan,et al.  Comparison of biological characteristics of mesenchymal stem cells derived from the human umbilical cord and decidua parietalis , 2019, Molecular medicine reports.

[14]  Jie Hao,et al.  Comparative analysis of mesenchymal stem cells derived from amniotic membrane, umbilical cord, and chorionic plate under serum-free condition , 2019, Stem Cell Research & Therapy.

[15]  X. Tian,et al.  Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells , 2018, Stem cells international.

[16]  Yuan Yuan,et al.  Association of IL10 gene promoter polymorphisms with risks of gastric cancer and atrophic gastritis , 2018, The Journal of international medical research.

[17]  M. Suematsu,et al.  CAPZA1 determines the risk of gastric carcinogenesis by inhibiting Helicobacter pylori CagA-degraded autophagy , 2018, Autophagy.

[18]  I. Choi,et al.  Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer , 2018, The New England journal of medicine.

[19]  R. Hunt,et al.  Gastric Cancer as Preventable Disease , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[20]  K. Koike,et al.  Metaplasia in the Stomach—Precursor of Gastric Cancer? , 2017, International journal of molecular sciences.

[21]  D. Morgan,et al.  Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial , 2017, Gut.

[22]  Sun-Young Yang,et al.  Risk Factors for Gastric Tumorigenesis in Underlying Gastric Mucosal Atrophy , 2017, Gut and liver.

[23]  K. Hahm,et al.  The efficacy of human placenta-derived mesenchymal stem cells on radiation enteropathy along with proteomic biomarkers predicting a favorable response , 2017, Stem Cell Research & Therapy.

[24]  Tayyab Hamid Malik,et al.  Gastric Intestinal Metaplasia: An Intermediate Precancerous Lesion in the Cascade of Gastric Carcinogenesis. , 2017, Journal of the College of Physicians and Surgeons--Pakistan : JCPSP.

[25]  Y. Nakagawa,et al.  A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after Helicobacter pylori Eradication , 2016, PloS one.

[26]  Y. Yamaji,et al.  Endoscopic gastric atrophy is strongly associated with gastric cancer development after Helicobacter pylori eradication , 2016, Surgical Endoscopy.

[27]  M. Bogdan,et al.  Expression of Pentraxin 3 and Thrombospondin 1 in Gingival Crevicular Fluid during Wound Healing after Gingivectomy in Postorthodontic Patients , 2016, Journal of immunology research.

[28]  D. Graham,et al.  Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis. , 2016, Gastroenterology.

[29]  A. Berger,et al.  The role of C1q in recognition of apoptotic epithelial cells and inflammatory cytokine production by phagocytes during Helicobacter pylori infection , 2015, Journal of Inflammation.

[30]  M. Ebina,et al.  Mesenchymal stem cells correct inappropriate epithelial-mesenchyme relation in pulmonary fibrosis using stanniocalcin-1. , 2015, Molecular therapy : the journal of the American Society of Gene Therapy.

[31]  M. Ichinose,et al.  Myriad Functions of Stanniocalcin-1 (STC1) Cover Multiple Therapeutic Targets in the Complicated Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) , 2015, Clinical medicine insights. Circulatory, respiratory and pulmonary medicine.

[32]  P. Malfertheiner,et al.  Preneoplastic Conditions in the Stomach: Always a Point of No Return , 2014, Digestive Diseases.

[33]  I. Pinchuk,et al.  Immune evasion strategies used by Helicobacter pylori. , 2014, World journal of gastroenterology.

[34]  Shu-Yu Wu,et al.  Stanniocalcin-1 ameliorates lipopolysaccharide-induced pulmonary oxidative stress, inflammation, and apoptosis in mice. , 2014, Free radical biology & medicine.

[35]  K. Hahm,et al.  Special Licorice Extracts Containing Lowered Glycyrrhizin and Enhanced Licochalcone A Prevented Helicobacter pylori‐Initiated, Salt Diet‐Promoted Gastric Tumorigenesis , 2014, Helicobacter.

[36]  Katherine L. Cook,et al.  Thrombospondin-1 and CD47 signaling regulate healing of thermal injury in mice , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[37]  M. Bonneau,et al.  Repeated Autologous Bone Marrow‐Derived Mesenchymal Stem Cell Injections Improve Radiation‐Induced Proctitis in Pigs , 2013, Stem cells translational medicine.

[38]  A. Hutcheon,et al.  Role of thrombospondin-1 in repair of penetrating corneal wounds. , 2013, Investigative ophthalmology & visual science.

[39]  R. Gorodetsky,et al.  Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells , 2013, PloS one.

[40]  Xunbo Jin,et al.  Multi-therapeutic effects of human adipose-derived mesenchymal stem cells on radiation-induced intestinal injury , 2013, Cell Death and Disease.

[41]  T. Kwok,et al.  The impact of autophagic processes on the intracellular fate of Helicobacter pylori , 2013, Autophagy.

[42]  E. Mazzon,et al.  Foveolar cells phagocytose apoptotic neutrophils in chronic active Helicobacter pylori gastritis , 2012, Virchows Archiv.

[43]  M. Sweetwyne,et al.  Thrombospondin1 in tissue repair and fibrosis: TGF-β-dependent and independent mechanisms. , 2012, Matrix biology : journal of the International Society for Matrix Biology.

[44]  C. Wong,et al.  Evolution and roles of stanniocalcin , 2012, Molecular and Cellular Endocrinology.

[45]  K. Murakami,et al.  Helicobacter pylori Eradication Improves Gastric Atrophy and Intestinal Metaplasia in Long-Term Observation , 2012, Digestion.

[46]  Gang Huang,et al.  Interleukin-10-819 promoter polymorphism in association with gastric cancer risk , 2012, BMC Cancer.

[47]  C. Wong,et al.  Stanniocalcin-1 Regulates Re-Epithelialization in Human Keratinocytes , 2011, PloS one.

[48]  A. Hutcheon,et al.  Localization of thrombospondin-1 and myofibroblasts during corneal wound repair. , 2011, Experimental eye research.

[49]  G. F. Wagner,et al.  The renal stanniocalcin-1 gene is differentially regulated by hypertonicity and hypovolemia in the rat , 2011, Molecular and Cellular Endocrinology.

[50]  P. Laloi,et al.  Mesenchymal stem cells improve small intestinal integrity through regulation of endogenous epithelial cell homeostasis , 2010, Cell Death and Differentiation.

[51]  T. Toyokawa,et al.  Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: A long‐term prospective cohort study , 2010, Journal of gastroenterology and hepatology.

[52]  D. Sheikh-Hamad.  Mammalian stanniocalcin-1 activates mitochondrial antioxidant pathways: new paradigms for regulation of macrophages and endothelium. , 2010, American journal of physiology. Renal physiology.

[53]  O. Monni,et al.  15-Hydroxyprostaglandin Dehydrogenase Is Down-regulated in Gastric Cancer , 2009, Clinical Cancer Research.

[54]  C. Sorenson,et al.  Attenuation of proliferation and migration of retinal pericytes in the absence of thrombospondin-1. , 2009, American journal of physiology. Cell physiology.

[55]  R. Pochampally,et al.  Multipotent Stromal Cells Are Activated to Reduce Apoptosis in Part by Upregulation and Secretion of Stanniocalcin‐1 , 2009, Stem cells.

[56]  L. Xiang,et al.  Fetal liver-conditioned medium induces hepatic specification from mouse bone marrow mesenchymal stromal cells: a novel strategy for hepatic transdifferentiation. , 2008, Cytotherapy.

[57]  Nayoung Kim,et al.  Gastric Mucosal Protection via Enhancement of MUC5AC and MUC6 by Geranylgeranylacetone , 2005, Digestive Diseases and Sciences.

[58]  J. Aubin,et al.  Stanniocalcin 1 as a pleiotropic factor in mammals , 2004, Peptides.

[59]  F. Peale,et al.  Stanniocalcin 1 Is an Autocrine Modulator of Endothelial Angiogenic Responses to Hepatocyte Growth Factor* , 2003, Journal of Biological Chemistry.

[60]  K. Ishibashi,et al.  Prospect of a stanniocalcin endocrine/paracrine system in mammals. , 2002, American journal of physiology. Renal physiology.

[61]  R. P. Blankfield,et al.  Helicobacter pylori infection and the development of gastric cancer. , 2001, The New England journal of medicine.

[62]  M. Stolte,et al.  Atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach: a reality or merely an hypothesis? , 2001, Best practice & research. Clinical gastroenterology.

[63]  N. Sasaki,et al.  Helicobacter pylori infection and the development of gastric cancer. , 2001, The New England journal of medicine.

[64]  T. Ohkusa,et al.  Improvement in Atrophic Gastritis and Intestinal Metaplasia in Patients in Whom Helicobacter pylori Was Eradicated , 2001, Annals of Internal Medicine.