96
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Systematic investigation of oxygen and growth factors in clinically valid ex vivo expansion of cord blood CD34+ hematopoietic progenitor cells

, , &
Pages 679-685 | Received 09 Oct 2011, Accepted 06 Feb 2012, Published online: 16 Mar 2012
 

Abstract

Background aims. Cord blood is considered to be a superior source of hematopoietic stem and progenitor cells for transplantation, but clinical use is limited primarily because of the low numbers of cells harvested. Ex vivo expansion has the potential to provide a safe, effective means of increasing cell numbers. However, an absence of consensus regarding optimum expansion conditions prevents standard implementation. Many studies lack clinical applicability, or have failed to investigate the combinational effects of different parameters. Methods. This is the first study to characterize systematically the effect of growth factor combinations across multiple oxygen levels on the ex vivo expansion of cord blood CD34+ hematopoietic cells utilizing clinically approvable reagents and methodologies throughout. Results. Optimal fold expansion, as assessed both phenotypically and functionally, was greatest with thrombopoietin, stem cell factor, Flt-3 ligand and interleukin-6 at an oxygen level of 10%. With these conditions, serial expansion showed continual target population expansion and consistently higher expression levels of self-renewal associated genes. Conclusions. This study has identified optimized fold expansion conditions, with the potential for direct clinical translation to increase transplantable cell dose and as a baseline methodology against which future factors can be tested.

Acknowledgements

The authors would like to thank Joel R. Symons and Anthea M. Reid for CD34+ cell enrichment and cryopreservation, and Dr Cynthia S. Wong and Dr Malte C. Ebach for helpful discussions and advice.

Disclosure of interest: This work was supported by an Advanced Manufacturing CRC grant, and by research funding from Barwon Health (Geelong, Australia), Cytomatrix Pty Ltd (Australia) and the School of Medicine, Deakin University (Waurn Ponds, Australia).

MLT, FMC and MAK designed the research. MLT performed the majority of research, data collection and statistical analysis, with FMC providing assistance. MLT wrote the manuscript. All authors participated in data interpretation and manuscript drafting. MLT is a PhD candidate and this work forms part of this PhD.

MLT, FMC and MAK have ownership interests in Cytomatrix Pty Ltd, which has been a part-employer of MLT and MAK. Furthermore, MAK is the current CEO and CSO of Cytomatrix Pty Ltd. ACW declares no conflict of interest.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.