title: Bone marrow transplantation rescues intestinal mucosa after whole body radiation via paracrine mechanisms.
abstract: OBJECTIVE
  Our previous study reveals bone marrow transplantation (BMT) recruits host marrow-derived myelomonocytic cells to radiation-injured intestine, enhancing stromal proliferation, leading secondarily to epithelial regeneration. In this study, we propose BMT ameliorates intestinal damage via paracrine mechanisms.
  
  
  METHODS
  Angiogenic cytokines within the intestinal mucosa of mice after whole body irradiation (WBI) with or without BMT were measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused into mice for three days after radiation. Carrageenan was used to deplete myelomonocytic cells of mice.
  
  
  RESULTS
  BMT increased VEGF, bFGF and other angiogenic and chemotactic cytokines in the intestinal mucosa within 24h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage with improved stromal activity and prolonged survival of mice. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to the intestine. Pretreatment of carrageenan to recipient mice reversed some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal mucosa after BMT.
  
  
  CONCLUSIONS
  Our result suggests BMT recruits host myelomonocytic cells and enhances intestinal stroma proliferation after radiation by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic cells further uplift the paracrine effect to enhance intestinal mucosal recovery.
authors.affiliation: National Health Research Institutes, Tainan, Taiwan.
authors.forename: Ya Hui
authors.initials: YH
authors.lastname: Chang
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Lin
authors.forename: Chi-Wen
authors.initials: CW
authors.lastname: Lou
authors.forename: Chuan-Kai
authors.initials: CK
authors.lastname: Chou
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Ch'ang
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000378:metabolism / Q000628:therapy; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D053208:Kaplan-Meier Estimate; D051379:Mice; D008810:Mice, Inbred C57BL; D019899:Paracrine Communication; D011833:Radiation Injuries, Experimental; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014916:Whole-Body Irradiation
chemical_list: D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017526:Receptor, IGF Type 1