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TISSUE-SPECIFIC STEM CELLS

Small Peptide Analogue of SDF-1 Supports Survival of Cord Blood CD34⁺ Cells in Synergy with Other Cytokines and Enhances Their Ex Vivo Expansion and Engraftment into Nonobese Diabetic/Severe Combined Immunodeficient Mice

^a Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China;
^b Chemokine Therapeutics Corporation, Vancouver, British Columbia, Canada

Key Words. SDF-1 • Cord blood CD34⁺ cells • Ex vivo expansion • Engraftment • Nonobese diabetic/severe combined immunodeficient mice • CXCR4

Correspondence: Karen Li, Ph.D., Associate Professor, Department of Paediatrics, The Chinese University of Hong Kong, 6th Floor, Clinical Sciences Block, Prince of Wales Hospital, Shatin, NT, Hong Kong, People’s Republic of China. Telephone: 852-2632-2859; Fax: 852-2636-0020; e-mail: lipang{at}cuhk.edu.hk

The SDF-1/CXCR4 axis has been implicated in the chemotaxis, homing, mobilization, and expansion of hematopoietic stem and progenitor cells. We studied the effects of a SDF-1 peptide analogue CTCE-0214 on the survival of cord blood CD34⁺ cells in culture, expansion, and engraftment of expanded cells in the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model. Our results demonstrated that CTCE-0214 synergized with thrombopoietin (TPO), stem cell factor (SCF), or flt-3 ligand (FL) on the survival of stem and progenitor cells in culture. Adding CTCE-0214 at a low concentration (0.01 ng/ml) for 4 days together with TPO, SCF, and FL significantly enhanced ex vivo expansion of CD34⁺ cells to subsets of primitive (CD34⁺CD38^– cells, colony-forming unit-mixed [CFU-GEMMs]), erythroid (CFU-Es), myeloid (CFU-GMs), and megakaryocytic (CD61⁺CD41⁺ cells, CFU-MKs) progenitors, as well as their multilineage engraftment in NOD/SCID mice. Interestingly, the short exposure of expanded cells to CTCE-0214 (100 and 500 ng/ml) for 4 hours did not increase the quantity of progenitor cells but enhanced their engraftment capacity. The proportion of CD34⁺ cells expressing surface CXCR4 was decreased, but the overall number of this population increased upon expansion. The small peptide analogue of SDF-1 could be developed for ex vivo expansion and improving engraftment of cord blood transplantation.

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