title: Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases.
abstract: Human dental pulp cells (hDPCs) are a valuable source for the generation of patient-specific human induced pluripotent stem cells (hiPSCs). An advanced strategy for the safe and efficient reprogramming of hDPCs and subsequent lineage-specific differentiation is a critical step toward clinical application. In present research, we successfully generated hDPC-iPSCs using only two non-oncogenic factors: Oct4 and Sox2 (2F hDPC-hiPSCs) and evaluated the feasibility of hDPC-iPSCs as substrates for endothelial progenitor cells (EPCs), contributing to EPC-based therapies. Under conventional differentiation conditions, 2F hDPC-hiPSCs showed higher differentiation efficiency, compared to hiPSCs from other cell types, into multipotent CD34(+) EPCs (2F-hEPCs) capable to differentiate into functional endothelial and smooth muscle cells. The angiogenic and neovasculogenic activities of 2F-hEPCs were confirmed using a Matrigel plug assay in mice. In addition, the therapeutic effects of 2F-hEPC transplantation were confirmed in mouse models of hind-limb ischemia and myocardial infarction. Importantly, 2F-EPCs effectively integrated into newly formed vascular structures and enhanced neovascularization via likely both direct and indirect paracrine mechanisms. 2F hDPC-hiPSCs have a robust capability for the generation of angiogenic and vasculogenic EPCs, representing a strategy for patient-specific EPC therapies and disease modeling, particularly for ischemic vascular diseases.
authors.affiliation: Stem Cells Research Center, KRIBB, Daejeon, Republic of Korea.
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Yoo
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Na
authors.forename: Dong-Seol
authors.initials: DS
authors.lastname: Lee
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Heo
authors.forename: Yuri
authors.initials: Y
authors.lastname: An
authors.forename: Junghwa
authors.initials: J
authors.lastname: Cha
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Park
authors.forename: Yee Sook
authors.initials: YS
authors.lastname: Cho
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003782:Dental Pulp; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D006614:Hindlimb / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007511:Ischemia / Q000628:therapy*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy; D033581:Stem Cell Transplantation; D014652:Vascular Diseases / Q000628:therapy*
keywords: Dental pulp cells; Endothelial progenitor cells; Inducible ischemia; Myocardial infarction; Stem cell