Differential maturation of megakaryocyte progenitor cells from cord blood and mobilized peripheral blood.
OBJECTIVE
In comparison with stem cell transplantation using bone marrow or cytokine-mobilized peripheral blood, cord blood transplantation is characterized by delayed engraftment, in particular platelet recovery. The differences in the kinetics of engraftment may be related to quantitative differences in the numbers of stem cells and megakaryocyte progenitor cells and/or to qualitative differences between megakaryocyte progenitor cells in these grafts. We compared the hematopoietic composition of these grafts and determined the distribution of mature and immature megakaryocyte progenitor cells in cord blood and mobilized peripheral blood and their in vitro kinetic behavior.


METHODS
Megakaryocyte progenitor cell subpopulations from cord blood (CB) and mobilized peripheral blood (PBSC) were expanded in vitro in the presence of mpl-ligand. The developmental differences during expansion of megakaryocyte progenitors were analyzed by flow cytometry and progenitor assays.


RESULTS
We found that the immature (CD34(+)/CD41(-)) subpopulation from CB contains more than 98% of all megakaryocyte progenitor cells, responsible for 99% of all megakaryocytic cells cultured during 2 weeks. The CB CD34(+)/CD41(+) subpopulation shows no contribution to megakaryocytic cell formation. In contrast, in PBSC the mature (CD34(+)/CD41(+)) subpopulation contains 7% of all megakaryocyte progenitor cells. Moreover, CD34(+) cells from CB and PBSC also showed distinct phenotypic differences during maturation in vitro. PBSC megakaryocyte progenitor cells transiently express both CD34 and CD41 during maturation in vitro, whereas CB progenitor cells transiently lack expression of both markers before differention into (CD34(-)/CD41(+)) megakaryocytic cells.


CONCLUSIONS
The in vitro data indicate the presence of different developmental stages of megakaryocyte progenitor cells in CB as compared to PBSC. These differences in composition and maturation between CB and PBSC may be related to the different kinetics of engraftment following transplantation of these stem cell sources.
Schipper
Laurus F
LF
Blood Bank Leiden-Haaglanden, Leiden, The Netherlands. lfschip@wxs.nl
Brand
Anneke
A
Reniers
Nathalie
N
Melief
Cees J J
CJ
Willemze
Roel
R
Fibbe
Willem E
WE
D018952:Antigens, CD34 / Q000032:analysis; D002452:Cell Count; D002455:Cell Division; D002469:Cell Separation; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D004921:Erythropoietin / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007377:Interleukin-3 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D036102:Peripheral Blood Stem Cell Transplantation; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology
D018952:Antigens, CD34; D007377:Interleukin-3; D040201:Platelet Membrane Glycoprotein IIb; D019089:Stem Cell Factor; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin