Email updates

Keep up to date with the latest news and content from BMC Proceedings and BioMed Central.

This article is part of the supplement: São Paulo Advanced School of Comparative Oncology: Abstracts

Open Access Oral presentation

Hematopoietic stem cells have an intrinsic expansion limit

Shanti Rojas-Sutterlin*, André Haman and Trang Hoang

Author Affiliations

Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Canada

For all author emails, please log on.

BMC Proceedings 2013, 7(Suppl 2):O6  doi:10.1186/1753-6561-7-S2-O6


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1753-6561/7/S2/O6


Published:4 April 2013

© 2013 Rojas-Sutterlin et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Hematopoietic stem cell (HSC) transplantation is the only treatment providing long-term cure in acute myeloblastic leukemia. At the apex of the hematopoietic system, quiescent HSCs escape to chemotherapeutic treatments and therefore can regenerate the entire blood system after drug exposure. Nevertheless, the consequence of repeated chemotherapy regimen on HSC function remains to be clarified. In this study, we investigate how massive expansion in vivo influence HSC functions.

Methods and results

We optimized a protocol based on 5-fluorouracil (5FU), an antimetabolite used to treat different types of cancers. We show that after one 5FU treatment, HSCs exit quiescence and enter the cell cycle. To deplete cycling HSCs, we injected a second dose of 5FU and show that the stem cell pool is disseminated. Nonetheless, the remaining HSCs proliferate extensively to re-establish the HSC pool. At this point, most HSCs have exited the cell cycle and are back to quiescence. Despite a near normal stem cell pool size and a quiescent status, HSCs from these 5FU treated mice cannot compete against untreated cells to regenerate the host in transplantation assays. Furthermore, we show that this extensive proliferation in vivo severely impairs the clonal expansion of individual HSC as measured by the mean activity of stem cell (MAS).

Conclusion

Our results demonstrate that HSCs loose their competitive potential after two 5FU treatments, suggesting that HSCs have an intrinsic expansion limit beyond which their regenerative potential is impaired. We surmise that chemotherapy regimens based on repeated administration of antimetabolites are likely to impair long-term stem cell functions.

Financial support

FRSQ, Cole Foundation.