Human umbilical cord blood-derived f-macrophages retain pluripotentiality after thrombopoietin expansion.
We have previously characterized a new type of stem cell from human peripheral blood, termed fibroblast-like macrophage (f-Mphi). Here, using umbilical cord blood as a source, we identified cells with similar characteristics including expression of surface markers (CD14, CD34, CD45, CD117, and CD163), phagocytosis, and proliferative capacity. Further, thrombopoietin (TPO) significantly stimulated the proliferation of cord blood-derived f-Mphi (CB f-Mphi) at low dosage without inducing a megakaryocytic phenotype. Additional experiments demonstrated that TPO-expanded cord blood-derived f-Mphi (TCB f-Mphi) retained their surface markers and differentiation ability. Treatment with vascular endothelial cell growth factor (VEGF) gave rise to endothelial-like cells, expressing Flt-1, Flk-1, von Willebrand Factor (vWF), CD31, acetylated low density lipoprotein internalization, and the ability to form endothelial-like cell chains. In the presence of lipopolysaccharide (LPS) and 25 mM glucose, the TCB f-Mphi differentiated to express insulin mRNA, C-peptide, and insulin. In vitro functional analysis demonstrated that these insulin-positive cells could release insulin in response to glucose and other secretagogues. These findings demonstrate a potential use of CB f-Mphi and may lead to develop new therapeutic strategy for treating dominant disease.
Zhao
Yong
Y
Section of Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 W. Polk Street, Chicago, IL 60612, USA. yongzhao@uic.edu
Mazzone
Theodore
T
D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology; D005312:Fetal Blood / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010587:Phagocytosis; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013926:Thrombopoietin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D015703:Antigens, CD; D007328:Insulin; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D013926:Thrombopoietin; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D005947:Glucose