title: Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling.
abstract: The prospect of using endothelial progenitors is currently hampered by their low engraftment upon transplantation. We report that mesenchymal stem/stromal cells (MSCs), independent of source and age, improve the engraftment of endothelial colony forming cells (ECFCs). MSC coculture altered ECFC appearance to an elongated mesenchymal morphology with reduced proliferation. ECFC primed via MSC contact had reduced self-renewal potential, but improved capacity to form tube structures in vitro and engraftment in vivo Primed ECFCs displayed major differences in transcriptome compared to ECFCs never exposed to MSCs, affecting genes involved in the cell cycle, up-regulating of genes influencing mesenchymal transition, adhesion, extracellular matrix. Inhibition of NOTCH signaling, a potential upstream regulator of mesenchymal transition, in large part modulated this gene expression pattern and functionally reversed the mesenchymal morphology of ECFCs. The collective results showed that primed ECFCs survive better and undergo a mesenchymal transition that is dependent on NOTCH signaling, resulting in significantly increased vasculogenic potential.-Shafiee, A., Patel, J., Wong, H. Y., Donovan, P., Hutmacher, D. W., Fisk, N. M., Khosrotehrani, K. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling.
authors.affiliation: University of Queensland (UQ) Centre for Clinical Research, The University of Queensland, Brisbane, Queensland Australia.|Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.affiliation: University of Queensland (UQ) Centre for Clinical Research, The University of Queensland, Brisbane, Queensland Australia.
authors.forename: Jatin
authors.initials: J
authors.lastname: Patel
authors.affiliation: University of Queensland (UQ) Centre for Clinical Research, The University of Queensland, Brisbane, Queensland Australia.
authors.forename: Ho Yi
authors.initials: HY
authors.lastname: Wong
authors.affiliation: UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, Queensland, Australia; and.
authors.forename: Prudence
authors.initials: P
authors.lastname: Donovan
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
authors.affiliation: University of Queensland (UQ) Centre for Clinical Research, The University of Queensland, Brisbane, Queensland Australia.|Centre for Advanced Prenatal Care, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.affiliation: University of Queensland (UQ) Centre for Clinical Research, The University of Queensland, Brisbane, Queensland Australia; k.khosrotehrani@uq.edu.au.|UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, Queensland, Australia; and.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosrotehrani
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D010920:Placenta; D011247:Pregnancy; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051880:Receptors, Notch
keywords: ECFC; primed ECFC; vacularization