HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0560v1 26/11/2974    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Larsen, S. R. Articles by Rasko, J. E.J. Search for Related Content PubMed PubMed Citation Articles by Larsen, S. R. Articles by Rasko, J. E.J.

TRANSLATIONAL AND CLINICAL RESEARCH

Improved Granulocyte Colony-Stimulating Factor Mobilization of Hemopoietic Progenitors Using Cytokine Combinations in Primates

^aGene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Sydney, New South Wales, Australia;
^bInstitute of Haematology and
^cCell and Molecular Therapies, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

Key Words. Peripheral blood stem cells • Mobilization • Cytokines • Thrombopoietin • Granulocyte colony-stimulating factor • Nonhuman primate

Correspondence: Correspondence: John Rasko, Ph.D., Gene and Stem Cell Therapy Program, Centenary Institute, Amgen, Thousand Oaks, CA, http://www.amgen.com, Locked Bag No. 6, Newtown, New South Wales 2042, Australia. Telephone: 61-2-9565-6156; Fax: 61-2-9565-6101; e-mail: j.rasko{at}centenary.usyd.edu.au

Received on June 9, 2008; accepted for publication on August 6, 2008.

First published online in STEM CELLS EXPRESS  August 21, 2008.

Peripheral blood stem cells (PBSCs), usually mobilized with granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy, are the preferred source of cells for hemopoietic stem cell transplantation. Up to 25% of otherwise eligible transplant recipients fail to harvest adequate PBSCs. Therefore it is important to investigate existing and novel reagents to improve PBSC mobilization. Because of marked interindividual variation in humans, we developed a robust nonhuman primate model that allows the direct comparison of the efficacy of two PBSC mobilization regimens within the same animal. Using this model, we compared pegylated G-CSF (pegG-CSF) with standard G-CSF and compared the combination of G-CSF and pegylated megakaryocyte growth and development factor (pegMGDF) with G-CSF plus stem cell factor (SCF) by measuring the levels of CD34⁺ cells, colony-forming cells (CFCs), and SCID repopulating cells (SRCs) before and after cytokine administration. Mobilization of CD34⁺ cells, CFCs and SRCs using pegG-CSF achieved similar levels to those resulting from 5 days of standard G-CSF. The combination of G-CSF+pegMGDF mobilized progenitors to levels similar to G-CSF+SCF but greater than standard G-CSF for CD34⁺ cells and CFC. This first direct comparison of PBSC mobilization in individual primates demonstrates that peg-G-CSF is equivalent to daily G-CSF and that the addition of pegMGDF to G-CSF improves mobilization. In light of the development of new thrombopoietin agonists, these data offer the potential for improved stem cell mobilization strategies.

Disclosure of potential conflicts of interest is found at the end of this article.