| First Author | Hayase E | Year | 2024 |
| Journal | Blood Adv | Volume | 8 |
| Issue | 3 | Pages | 725-731 |
| PubMed ID | 38147622 | Mgi Jnum | J:352247 |
| Mgi Id | MGI:7581138 | Doi | 10.1182/bloodadvances.2023011034 |
| Citation | Hayase E, et al. (2024) R-Spondin1 protects gastric stem cells and mitigates gastric GVHD in allogeneic hematopoietic stem cell transplantation. Blood Adv 8(3):725-731 |
| abstractText | Graft-versus-host disease (GVHD) is the major obstacle to performing allogeneic hematopoietic cell transplantation (allo-HCT). We and others have shown that intestinal stem cells are targeted in lower gastrointestinal GVHD. A leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)-expressing gastric stem cells (GSCs) reside at the base of the gastric glands in mice. After experimental allo-HCT, Lgr5+ GSCs significantly decreased. Parietal cells, which underwent continuous renewal by GSCs, were injured in gastric GVHD, leading to failure of gastric acidification and aerobic bacterial overgrowth in the duodenum. Fate-mapping analysis demonstrated that administration of R-Spondin1 (R-Spo1) that binds to Lgr5 for 6 days in naive mice significantly increased proliferating epithelial cells derived from Lgr5+ GSCs. R-Spo1 administered on days -3 to -1 and from days +1 to +3 of allo-HCT protected GSCs, leading to amelioration of gastric GVHD and restoration of gastric acidification, and suppression of aerobic bacterial overgrowth in the duodenum. In conclusion, Lgr5+ GSCs were targeted by gastric GVHD, resulting in disruption of the gastric homeostasis, whereas R-Spo1 protected Lgr5+ GSCs from GVHD and maintained homeostasis in the stomach. |
