International Journal of Hematology

DOI: 10.1007/s12185-012-1233-4 Pages: 58-72

Hematopoietic recovery following chemotherapy is improved by BADGE-induced inhibition of adipogenesis

1. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Peking University People’s Hospital and Peking University Institute of Hematology

2. 4th Clinical Medical College of Peking University, Department of Hematology, Beijing Ji Shui Tan Hospital

3. Key Laboratory of Molecular Cardiovascular Science, Institute of Vascular Medicine, Peking University Third Hospital

Correspondence to:
Kai-Yan Liu
Tel: +86-10-88324958
Fax: +86-10-88324577
Email: liukaiyan@medmail.com.cn

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Abstract

This study was designed to investigate the role of increased adipocytes in the bone marrow (BM) niche induced by high-dose chemotherapy in hematopoietic recovery. Arabinosylcytosine (Ara-C) was administered to adult C57BL/6J mice to induce adipogenesis in the BM. We investigated the effects of adipogenesis on hematopoietic recovery following chemotherapy, using the peroxisome proliferator-activated receptor gamma inhibitor, bisphenol A diglycidyl ether (BADGE). Adipocyte hyperplasia could be induced by Ara-C treatment in BM and inhibited by BADGE. The accelerated recovery of leukocyte counts, increased colony forming units, and a higher proportion of Ki67+CD45+ BM cells and Ki67+LinSca1+c-kit+ hematopoietic stem cells were observed in the long bone marrow of adipocyte-inhibited mice, as well as an increase in the number of CD45+ BM cells in the tail fatty marrow compared to controls. Adipocytes participated in creating a distinctive niche for hematopoietic cells. In addition, lower expression of stromal cell-derived factor-1α and hypoxia-inducible factor-1 alpha were detected in the BADGE-treated group. These results indicate that hematopoietic recovery is improved following chemotherapy in adipogenesis-inhibited mice. In addition, adipocytes may create an individual niche that affects the proliferation and migration of hematopoietic cells in vitro and in vivo.

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