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望月 牧子
Department School of Medicine, School of Medicine Position Assistant Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Ex vivo expansion of human hematopoietic stem cells by garcinol, a potent inhibitor of histone acetyltransferase. |
| Journal | Formal name：PloS one Abbreviation：PLoS One ISSN code：19326203/19326203 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 6(9),pp.e24298 |
| Author and coauthor | Nishino Taito, Wang Changshan, Mochizuki-Kashio Makiko, Osawa Mitsujiro, Nakauchi Hiromitsu, Iwama Atsushi |
| Publication date | 2011 |
| Summary | BACKGROUND:Human cord blood (hCB) is the main source of hematopoietic stem and progenitor cells (HSCs/PCs) for transplantation. Efforts to overcome relative shortages of HSCs/PCs have led to technologies to expand HSCs/PCs ex vivo. However, methods suitable for clinical practice have yet to be fully established.METHODOLOGY/PRINCIPAL FINDINGS:In this study, we screened biologically active natural products for activity to promote expansion of hCB HSCs/PCs ex vivo, and identified Garcinol, a plant-derived histone acetyltransferase (HAT) inhibitor, as a novel stimulator of hCB HSC/PC expansion. During a 7-day culture of CD34(+)CD38(-) HSCs supplemented with stem cell factor and thrombopoietin, Garcinol increased numbers of CD34(+)CD38(-) HSCs/PCs more than 4.5-fold and Isogarcinol, a derivative of Garcinol, 7.4-fold. Furthermore, during a 7-day culture of CD34(+) HSCs/PCs, Garcinol expanded the number of SCID-repopulating cells (SRCs) 2.5-fold. We also demonstrated that the capacity of Garcinol and its derivatives to expand HSCs/PCs was closely correlated with their inhibitory effect on HAT. The Garcinol derivatives which expanded HSCs/PCs inhibited the HAT activity and acetylation of histones, while inactive derivatives did not.CONCLUSIONS/SIGNIFICANCE:Our findings identify Garcinol as the first natural product acting on HSCs/PCs and suggest the inhibition of HAT to be an alternative approach for manipulating HSCs/PCs. |
| DOI | 10.1371/journal.pone.0024298 |
| PMID | 21931675 |