Original Article

Bone Marrow Transplantation (2006) 37, 359–366. doi:10.1038/sj.bmt.1705258; published online 9 January 2006

Cord Blood Stem Cells

Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells

S N Robinson1, J Ng1, T Niu1, H Yang1, J D McMannis1, S Karandish1, I Kaur1, P Fu1, M Del Angel1, R Messinger1, F Flagge1, M de Lima1, W Decker1, D Xing1, R Champlin1 and E J Shpall1

1Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr SN Robinson, Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 65, Houston, TX 77030-4009, USA. E-mail: snrobins@mdanderson.org

Received 19 September 2005; Revised 1 November 2005; Accepted 11 November 2005; Published online 9 January 2006.

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Abstract

One factor limiting the therapeutic efficacy of cord blood (CB) hematopoietic progenitor cell (HPC) transplantation is the low cell dose of the graft. This is associated with an increased incidence of delayed or failed engraftment. Cell dose can be increased and the efficacy of CB transplantation potentially improved, by ex vivo CB expansion before transplantation. Two ex vivo CB expansion techniques were compared: (1) CD133+ selection followed by ex vivo liquid culture and (2) co-culture of unmanipulated CB with bone-marrow-derived mesenchymal stem cells (MSCs). Ex vivo culture was performed in medium supplemented with granulocyte colony-stimulating factor, stem cell factor and either thrombopoietin or megakaryocyte growth and differentiation factor. Expansion was followed by measuring total nucleated cell (TNC), CD133+ and CD34+ cell, colony-forming unit and cobblestone area-forming cell output. When compared to liquid culture, CB-MSC co-culture (i) required less cell manipulation resulting in less initial HPC loss and (ii) markedly improved TNC and HPC output. CB-MSC co-culture therefore holds promise for improving engraftment kinetics in CB transplant recipients.

Keywords:

cord blood, ex vivo expansion, mesenchymal stem cell, CD34+, CD133+, cobblestone area-forming cell assay

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