title: Fibrin acts as biomimetic niche inducing both differentiation and stem cell marker expression of early human endothelial progenitor cells.
abstract: OBJECTIVE
  Transplantation of endothelial progenitor cells (EPCs) is a promising approach for revascularization of tissue. We have used a natural and biocompatible biopolymer, fibrin, to induce cell population growth, differentiation and functional activity of EPCs.
  
  
  METHODS
  Peripheral blood mononuclear cells were cultured for 1 week to obtain early EPCs. Fibrin was characterized for stiffness and capability to sustain cell population expansion at different fibrinogen-thrombin ratios. Viability, differentiation and angiogenic properties of EPCs were evaluated and compared to those of EPCs grown on fibronectin.
  
  
  RESULTS
  Fibrin had a nanometric fibrous structure forming a porous network. Fibrinogen concentration significantly influenced fibrin stiffness and cell growth: 9 mg/ml fibrinogen and 25 U/ml thrombin was the best ratio for enhanced cell viability. Moreover, cell viability was significantly higher on fibrin compared to being on fibronectin. Even though no significant difference was observed in expression of endothelial markers, culture on fibrin elicited marked induction of stem cell markers OCT 3/4 and NANOG. In vitro angiogenesis assay on Matrigel showed that EPCs grown on fibrin retain angiogenetic capability as EPCs grown on fibronectin, but significantly better release of cytokines involved in cell recruitment was produced by EPC grown on fibrin.
  
  
  CONCLUSIONS
  Fibrin is a suitable matrix for EPC growth, differentiation and angiogenesis capability, suggesting that fibrin gel may be very useful for regenerative medicine.
authors.affiliation: Cardiovascular Research Laboratory, University of Pisa, Pisa, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Barsotti
authors.forename: A
authors.initials: A
authors.lastname: Magera
authors.forename: C
authors.initials: C
authors.lastname: Armani
authors.forename: F
authors.initials: F
authors.lastname: Chiellini
authors.forename: F
authors.initials: F
authors.lastname: Felice
authors.forename: D
authors.initials: D
authors.lastname: Dinucci
authors.forename: A M
authors.initials: AM
authors.lastname: Piras
authors.forename: A
authors.initials: A
authors.lastname: Minnocci
authors.forename: R
authors.initials: R
authors.lastname: Solaro
authors.forename: G
authors.initials: G
authors.lastname: Soldani
authors.forename: A
authors.initials: A
authors.lastname: Balbarini
authors.forename: R
authors.initials: R
authors.lastname: Di Stefano
mesh_terms: D001672:Biocompatible Materials / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D040761:Biomimetic Materials / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000502:physiology*; D004727:Endothelium / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D005340:Fibrinogen / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D016062:Porosity; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D005353:Fibronectins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin