title: Leptin enhances endothelial cell differentiation and angiogenesis in murine embryonic stem cells.
abstract: The metabolic regulation of leptin and its angiogenic effects have been well characterized in adult mammals. However, the role of leptin in the differentiation of embryonic stem cells (ESCs) to endothelial cells (ECs) has not been characterized. We hypothesized that leptin enhances the generation of ECs derived from ESCs and, in this way, promotes angiogenesis in embryonic vessels. To address this hypothesis, we utilized an in vitro model consisting of murine ESCs-derived embryoid bodies (EBs). Vascular density, EC and angiogenesis markers as well as phosphorylation levels of signal transducer and activator of transcription 3 (pSTAT3) were investigated in leptin-treated EBs and in untreated EBs as controls. ESC-derived ECs were isolated by magnetic sorting based on the expression of platelet endothelial cell adhesion molecule (PECAM-1/CD31). Significant upregulation of EC and angiogenic markers as well as higher vessel density were found in leptin-treated EBs compared to controls. CD31 positive enriched cells derived from leptin-treated EBs had improved proliferation and survival rate and showed higher levels of pSTAT3. These results suggested that leptin promotes EC differentiation and angiogenesis in mouse EBs and that janus tyrosine kinase (JAK)/STAT pathway can play a role in this biological process. Leptin-mediated EC differentiation and angiogenesis in ESCs can be a useful application towards regenerative medicine and tissue engineering.
authors.affiliation: Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Kurtovic
authors.affiliation: Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Tina T
authors.initials: TT
authors.lastname: Ng
authors.affiliation: Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Ankur
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Vaithilingaraja
authors.initials: V
authors.lastname: Arumugaswami
authors.affiliation: Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Kira L
authors.initials: KL
authors.lastname: Chaiboonma
authors.affiliation: The Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Aminzadeh
authors.affiliation: The Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Makkar
authors.affiliation: Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA. Electronic address: donald.dafoe@cshs.org.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Dafoe
authors.affiliation: Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA. Electronic address: Talaverad@cshs.org.
authors.forename: Dodanim
authors.initials: D
authors.lastname: Talavera-Adame
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058732:Embryoid Bodies / Q000187:drug effects / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D015415:Biomarkers; D020738:Leptin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053612:Janus Kinases
keywords: Angiogenesis; Differentiation; Embryonic stem cells; Endothelial cells; Leptin