PMID- 34435402 OWN - NLM STAT- MEDLINE DCOM- 20211012 LR - 20211012 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 54 IP - 10 DP - 2021 Oct TI - Bone marrow-derived mesenchymal stem cells promote Helicobacter pylori-associated gastric cancer progression by secreting thrombospondin-2. PG - e13114 LID - 10.1111/cpr.13114 [doi] LID - e13114 AB - OBJECTIVES: Bone marrow-derived cells (BMDCs), especially mesenchymal stem cells (MSCs), may be involved in the development of Helicobacter pylori-associated gastric cancer (GC) in mice, but the specific mechanism remains unclear, and evidence from human studies is lacking. MATERIALS AND METHODS: To verify the role of BM-MSCs in H pylori-associated GC, green fluorescent protein (GFP)-labelled BM-MSCs were transplanted into the subserosal layers of the stomach in a mouse model of chronic H pylori infection. Three months post-transplantation, the mice were sacrificed, and the gastric tissues were subjected to histopathological and immunofluorescence analyses. In addition, we performed fluorescence in situ hybridization (FISH) and immunofluorescence analyses of gastric tissue from a female patient with H pylori infection and a history of acute myeloid leukaemia who received a BM transplant from a male donor. RESULTS: In mice with chronic H pylori infection, GFP-labelled BM-MSCs migrated from the serous layer to the mucosal layer and promoted GC progression. The BM-MSCs differentiated into pan-cytokeratin-positive epithelial cells and alpha-smooth muscle actin-positive cancer-associated fibroblasts (CAFs) by secreting the protein thrombospondin-2. FISH analysis of gastric tissue from the female patient revealed Y-chromosome-positive cells. Immunofluorescence analyses further confirmed that Y-chromosome-positive cells showed positive BM-MSCs marker. These results suggested that allogeneic BMDCs, including BM-MSCs, can migrate to the stomach under chronic H pylori infection. CONCLUSIONS: Taken together, these findings imply that BM-MSCs participate in the development of chronic H pylori-associated GC by differentiating into both gastric epithelial cells and CAFs. CI - (c) 2021 The Authors. Cell Proliferation published by John Wiley & Sons Ltd. FAU - Shi, Huiying AU - Shi H AUID- ORCID: 0000-0002-0796-9944 AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Qi, Cuihua AU - Qi C AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Meng, Lingjun AU - Meng L AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Yao, Hailing AU - Yao H AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Jiang, Chen AU - Jiang C AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Fan, Mengke AU - Fan M AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Qin AU - Zhang Q AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Hou, Xiaohua AU - Hou X AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Lin, Rong AU - Lin R AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng GR - 2017YFC0110003/National key research and development program of China/ GR - 81272656/National Natural Science Foundation of China/ GR - 81572428/National Natural Science Foundation of China/ GR - 81974068/National Natural Science Foundation of China/ GR - 2017CFA061/Natural Science Foundation of Hubei Province/ PT - Journal Article DEP - 20210825 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 0 (Thrombospondins) SB - IM MH - Animals MH - Bone Marrow/*metabolism/microbiology MH - Bone Marrow Cells/*metabolism MH - Cell Differentiation/physiology MH - Cell Proliferation/physiology MH - Epithelial Cells/metabolism/microbiology MH - Female MH - Gastric Mucosa/*metabolism/microbiology MH - Helicobacter Infections/*metabolism/microbiology MH - Helicobacter pylori/pathogenicity MH - Humans MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Stomach Neoplasms/*metabolism/microbiology MH - Thrombospondins/*metabolism PMC - PMC8488559 OTO - NOTNLM OT - Helicobacter pylori OT - Bone marrow-derived mesenchymal stem cells (BM-MSCs) OT - Cancer-associated fibroblasts (CAFs) OT - Gastric cancer (GC) OT - Thrombospondin-2 COIS- None. EDAT- 2021/08/27 06:00 MHDA- 2021/10/13 06:00 PMCR- 2021/08/25 CRDT- 2021/08/26 06:31 PHST- 2021/07/26 00:00 [revised] PHST- 2021/06/01 00:00 [received] PHST- 2021/08/02 00:00 [accepted] PHST- 2021/08/27 06:00 [pubmed] PHST- 2021/10/13 06:00 [medline] PHST- 2021/08/26 06:31 [entrez] PHST- 2021/08/25 00:00 [pmc-release] AID - CPR13114 [pii] AID - 10.1111/cpr.13114 [doi] PST - ppublish SO - Cell Prolif. 2021 Oct;54(10):e13114. doi: 10.1111/cpr.13114. Epub 2021 Aug 25.