title: Role of Endothelial Progenitor Cells in Maintaining Stemness and Enhancing Differentiation of Mesenchymal Stem Cells by Indirect Cell-Cell Interaction.
abstract: A hot issue in current research regarding stem cells for regenerative medicine is the retainment of the stemness and multipotency of stem cell. Endothelial progenitor cells (EPCs) are characterized by an angiogenic switch that induces angiogenesis and further ameliorates the local microenvironment in ischemic organs. This study investigated whether EPCs could modulate the multipotent and differential abilities of mesenchymal stem cells (MSCs) in vitro and in vivo. We established an EPC/MSC indirect Transwell coculture system and then examined the effects of EPCs on the regulation of MSC biological properties in vitro and bone formation in vivo. The in vitro studies showed that cocultured MSCs (coMSCs) display no overt changes in cell morphology but an enhanced MSC phenotype compared with monocultured MSCs (monoMSCs). Our studies regarding the cellular, molecular, and protein characteristics of coMSCs and monoMSCs demonstrated that EPCs greatly promote the proliferation and differentiation potentials of coMSCs under indirect coculture condition. The expression of the pluripotency factors OCT4, SOX2, Nanog, and Klf4 was also upregulated in coMSCs. Furthermore, coMSCs combined with fibrin glue showed improved bone regeneration when used to repair rat alveolar bone defects compared with monoMSC grafts in vivo. This study is the first to demonstrate that EPCs have dynamic roles in maintaining MSC stemness and regulating MSC differentiation potential.
authors.affiliation: 1 Department of Orthodontics, School of Stomatology, Fourth Military Medical University , Xi'an, China .|2 Institute of Stomatology, Chinese PLA General Hospital , Beijing, China .
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.affiliation: 2 Institute of Stomatology, Chinese PLA General Hospital , Beijing, China .|3 Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University , Xi'an, China .
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2 Institute of Stomatology, Chinese PLA General Hospital , Beijing, China .
authors.forename: Ning
authors.initials: N
authors.lastname: Wen
authors.affiliation: 4 Department of Orthodontics, Dalian Stomatological Hospital , Dalian, China .
authors.forename: Gongjie
authors.initials: G
authors.lastname: Yuan
authors.affiliation: 5 Department of Pharmacy, Affiliated Hospital of Academy of Military Medical Sciences , Beijing, China .
authors.forename: Mingling
authors.initials: M
authors.lastname: Wen
authors.affiliation: 6 Department of Stomatology, 323 Hospital of the People's Liberation Army , Xi'an, China .
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 1 Department of Orthodontics, School of Stomatology, Fourth Military Medical University , Xi'an, China .
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: 1 Department of Orthodontics, School of Stomatology, Fourth Military Medical University , Xi'an, China .
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 2 Institute of Stomatology, Chinese PLA General Hospital , Beijing, China .
authors.forename: Chuan
authors.initials: C
authors.lastname: Cai
authors.affiliation: 7 Department of General Dentistry, 174th Hospital of Chinese PLA , Xiamen, China .
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1 Department of Orthodontics, School of Stomatology, Fourth Military Medical University , Xi'an, China .
authors.forename: Yin
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats