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

Jong Min Park; Young Min Han; Sun Jin Hwang; Seong Jin Kim; Ki Baik Hahm

doi:10.3164/jcbn.20-151

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

J Clin Biochem Nutr. 2021 Sep;69(2):188-202. doi: 10.3164/jcbn.20-151. Epub 2021 Mar 27.

Authors

Jong Min Park¹, Young Min Han², Sun Jin Hwang³, Seong Jin Kim³, Ki Baik Hahm^{3

4}

Affiliations

¹ College of Oriental Medicine, Daejeon University, Daehak-ro 62, Dong-gu, Daejeon 34520, Korea.
² Western Seoul Center, Korea Basic Science Institute, University-Industry Cooperate Building, 150 Bugahyeon-ro, Seodaemun-gu, Seoul 03759, Korea.
³ Medpacto Research Institute, Medpacto, Myungdal-ro 92, Seocho-gu, Seoul 06668, Korea.
⁴ CHA Cancer Preventive Research Center, CHA Bio Complex, CHA University, 330 Pangyo-dong, Bundang-gu, Seongnam 13497, Korea.

Abstract

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.

Keywords: H. pylori; STC-1; TSP-1; chronic atrophic gastritis; mesenchymal stem cells.