title: Vasculogenic and osteogenesis-enhancing potential of human umbilical cord blood endothelial colony-forming cells.
abstract: Umbilical cord blood-derived endothelial colony-forming cells (UCB-ECFC) show utility in neovascularization, but their contribution to osteogenesis has not been defined. Cocultures of UCB-ECFC with human fetal-mesenchymal stem cells (hfMSC) resulted in earlier induction of alkaline phosphatase (ALP) (Day 7 vs. 10) and increased mineralization (1.9×; p < .001) compared to hfMSC monocultures. This effect was mediated through soluble factors in ECFC-conditioned media, leading to 1.8-2.2× higher ALP levels and a 1.4-1.5× increase in calcium deposition (p < .01) in a dose-dependent manner. Transcriptomic and protein array studies demonstrated high basal levels of osteogenic (BMPs and TGF-βs) and angiogenic (VEGF and angiopoietins) regulators. Comparison of defined UCB and adult peripheral blood ECFC showed higher osteogenic and angiogenic gene expression in UCB-ECFC. Subcutaneous implantation of UCB-ECFC with hfMSC in immunodeficient mice resulted in the formation of chimeric human vessels, with a 2.2-fold increase in host neovascularization compared to hfMSC-only implants (p = .001). We conclude that this study shows that UCB-ECFC have potential in therapeutic angiogenesis and osteogenic applications in conjunction with MSC. We speculate that UCB-ECFC play an important role in skeletal and vascular development during perinatal development but less so in later life when expression of key osteogenesis and angiogenesis genes in ECFC is lower.
authors: Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Yuchun
authors: Y
authors: Liu
authors: Swee-Hin
authors: SH
authors: Teoh
authors: Mark S K
authors: MS
authors: Chong
authors: Eddy S M
authors: ES
authors: Lee
authors: Citra N Z
authors: CN
authors: Mattar
authors: Nau'shil Kaur
authors: NK
authors: Randhawa
authors: Zhi-Yong
authors: ZY
authors: Zhang
authors: Reinhold J
authors: RJ
authors: Medina
authors: Roger D
authors: RD
authors: Kamm
authors: Nicholas M
authors: NM
authors: Fisk
authors: Mahesh
authors: M
authors: Choolani
authors: Jerry K Y
authors: JK
authors: Chan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D046228:Microarray Analysis; D010012:Osteogenesis / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned