title: Infiltration of plasma rich in growth factors enhances in vivo angiogenesis and improves reperfusion and tissue remodeling after severe hind limb ischemia.
abstract: PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia.
authors.affiliation: Eduardo Anitua Foundation for Biomedical Research, Vitoria, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Anitua
authors.affiliation: Cell Therapy Program, Foundation for Applied Medical Research, University of Navarra, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.affiliation: BTI - Biotechnology Institute, Vitoria, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Prado
authors.affiliation: BTI - Biotechnology Institute, Vitoria, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Aguirre
authors.affiliation: Arthroscopic Surgery Unit, Hospital Vithas San Jose, Vitoria, Spain.
authors.forename: Mikel
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: Eduardo Anitua Foundation for Biomedical Research, Vitoria, Spain; BTI - Biotechnology Institute, Vitoria, Spain.
authors.forename: Sabino
authors.initials: S
authors.lastname: Padilla
authors.affiliation: Cell Therapy Program, Foundation for Applied Medical Research, University of Navarra, Spain.
authors.forename: Xabier L
authors.initials: XL
authors.lastname: Aranguren
authors.affiliation: Cell Therapy Program, Foundation for Applied Medical Research, University of Navarra, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.affiliation: Department of Nuclear Medicine, MicroPET Research Unit CIMA-CUN, Clínica Universitaria, University of Navarra, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Collantes
authors.affiliation: Hematology and Cell Therapy Department, Clínica Universidad de Navarra, University of Navarra, Spain.
authors.forename: Milagros
authors.initials: M
authors.lastname: Hernandez
authors.affiliation: Cell Therapy Program, Foundation for Applied Medical Research, University of Navarra, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Perez-Ruiz
authors.affiliation: Department of Nuclear Medicine, MicroPET Research Unit CIMA-CUN, Clínica Universitaria, University of Navarra, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Peñuelas
authors.affiliation: Eduardo Anitua Foundation for Biomedical Research, Vitoria, Spain. Electronic address: gorka.orive@ehu.es.
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
authors.affiliation: Cell Therapy Program, Foundation for Applied Medical Research, University of Navarra, Spain; Hematology and Cell Therapy Department, Clínica Universidad de Navarra, University of Navarra, Spain. Electronic address: fprosper@unav.es.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005355:Fibrosis; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D032446:Myoblasts / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010949:Plasma; D012038:Regeneration; D015424:Reperfusion
chemical_list: D036341:Intercellular Signaling Peptides and Proteins
keywords: Angiogenesis; Controlled release; Growth factors; Myogenesis; Platelet-rich plasma