Title |
Caffeic acid phenethyl ester promotes haematopoietic stem/progenitor cell homing and engraftment
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Published in |
Stem Cell Research & Therapy, November 2017
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DOI | 10.1186/s13287-017-0708-x |
Pubmed ID | |
Authors |
Xiaofang Chen, Yi Han, Bowen Zhang, Yiming Liu, Sihan Wang, Tuling Liao, Ziliang Deng, Zeng Fan, Jing Zhang, Lijuan He, Wen Yue, Yanhua Li, Xuetao Pei |
Abstract |
Several studies have suggested that caffeic acid phenethyl ester (CAPE) can induce the expression of hypoxia inducible factor-1α (HIF-1α) protein. We determined whether CAPE has a novel function in improving the homing and engraftment of haematopoietic stem/progenitor cells (HSPCs) by regulating HIF-1α gene expression in the bone marrow (BM) niche. For survival experiments, lethally irradiated C57BL/6 mice were injected with a low number of BM mononuclear cells (MNCs) and CAPE according to the indicated schedule. Homing efficiency analysis was conducted using flow cytometry and colony-forming unit (CFU) assays. The influence of intraperitoneal injection of CAPE on short-term and long-term engraftment of HSPCs was evaluated using competitive and non-competitive mouse transplantation models. To investigate the mechanism by which CAPE enhanced HSPC homing, we performed these experiments including Q-PCR, western blot, immunohistochemistry and CFU assays after in-vivo HIF-1α activity blockade. CAPE injection significantly increased the survival rate of recipient mice after lethal irradiation and transplantation of a low number of BM MNCs. Using HSPC homing assays, we found that CAPE notably increased donor HSPC homing to recipient BM. The subsequent short-term and long-term engraftment of transplanted HSPCs was also improved by the optimal schedule of CAPE administration. Mechanistically, we found that CAPE upregulated the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A) and stromal cell-derived factor 1α (SDF-1α). The HIF-1α inhibitor PX-478 blocked CAPE-enhanced HSPC homing, which supported the idea that HIF-1α is a key target of CAPE. Our results showed that CAPE administration facilitated HSPC homing and engraftment, and this effect was primarily dependent on HIF-1α activation and upregulation of SDF-1α and VEGF-A expression in the BM niche. |
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Mendeley readers
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Student > Bachelor | 2 | 14% |
Lecturer | 1 | 7% |
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Other | 1 | 7% |
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Nursing and Health Professions | 1 | 7% |
Other | 1 | 7% |
Unknown | 5 | 36% |