Small peptide analogue of SDF-1alpha 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.
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.
Li
Karen
K
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. lipang@cuhk.edu.hk
Chuen
Carmen Ka Yee
CK
Lee
Shuk Man
SM
Law
Ping
P
Fok
Tai Fai
TF
Ng
Pak Cheung
PC
Li
Chi Kong
CK
Wong
Donald
D
Merzouk
Ahmed
A
Salari
Hassan
H
Gu
Goldie Jia-Shi
GJ
Yuen
Patrick Man Pan
PM
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005312:Fetal Blood / Q000166:cytology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology*; D013926:Thrombopoietin / Q000494:pharmacology*
D018952:Antigens, CD34; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D013926:Thrombopoietin