Stem Cells
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First published online August 25, 2005
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2005-0082v1
24/1/55    most recent
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Submitted on February 27, 2005
Accepted on June 14, 2005

Original Article

Small peptide analog of SDF-1{alpha} supports survival of cord blood CD34+ cells in synergy with other cytokines, enhances their ex vivo expansion and engraftment into NOD/SCID mice

KAREN LI 1*, CARMEN KA YEE CHUEN 1, SHUK MAN LEE 1, PING LAW 2, TAI FAI FOK 1, PAK CHEUNG NG 1, CHI KONG LI 1, DONALD WONG 2, AHMED MERZOUK 2, HASSAN SALARI 2, GOLDIE JIA-SHI GU 1, PATRICK MAN PAN YUEN 1

1 Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong
2 Chemokine Therapeutics Corporation, Vancouver, BC, Canada

* To whom correspondence should be addressed. E-mail: lipang{at}cuhk.edu.hk.


  Abstract

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 analog CTCE-0214 on the survival of cord blood CD34+ cells in culture, expansion and engraftment of expanded cells in the 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 d 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 hr 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 analog of SDF-1 could be developed for ex vivo expansion and improving engraftment of cord blood transplantation.

Key Words. SDF-1, cord blood CD34+ cells, ex vivo expansion, engraftment, NOD/SCID mice, CXCR4




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