152P - Bone marrow transplantation rescues intestinal mucosa after whole body radiation via paracrine mechanisms

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Basic Science
Presenter Hui-Ju Chang
Authors H. Chang1, Y.H. Chang1, L. Lin1, C. Lou1, C. Chou2
  • 1National Institute Of Cancer Research, National Health Research Institutes, 704 - Tainan/TW
  • 2National Laboratory Animal Center, National Applied Research Laboratories, Taipei/TW

Abstract

Background

Our previous study reveals BM transplantation (BMT) triggers trafficking of host CD11b(+) myelomonocytic cells from the host marrow to the radiation-injured intestinal mucosa, enhancing the proliferation of intestinal stroma cells, leading secondarily to epithelial regeneration. In this study, we propose that BMT ameliorates intestinal damage via paracrine mechanisms.

Materials and methods

Mouse survival, intestine microcolony assay, angiogenic cytokine array, immunonhistochemical studies of both intestine and BM were evaluated in mice after WBI and BMT. Epithelial and stromal components within intestine mucosa were measured by immunoblotting and flowcytometry. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused to mice after WBI or whole abdomen irradiation. Carrageenan was used to deplete myelomonocytic cells of recipient mice.

Results

BMT increases VEGF, bFGF and other angiogenic cytokines within intestine mucosa within 24 hrs after WBI. Continuous infusion of BMCM alone ameliorated radiation-induced intestine damage and improved survival of mice. Proliferation index, endothelial cells, myofibroblasts as well as myelomonocytic cells within intestine were increased by BMCM within one week after radiation. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to intestine. Pretreatment of carrageenan to recipient mice depleted CD11b(+) myelomonocytic cells and reversed some of the angiogenic cytokine levels, including VEGF, within intestine mucosa after BMT from healthy donors.

Conclusions

Our results suggest that BMT recruits host CD11b(+) myelomonocytic cells and enhances intestine stroma proliferation by secreting angiogenic cytokines including PDGF, bFGF. Host CD11b(+) myelomonocytic cells further uplift the angiogenic effect via cytokines including VEGF.

Disclosure

All authors have declared no conflicts of interest.