title: Priming mobilized peripheral blood mononuclear cells with the "activated platelet supernatant" enhances the efficacy of cell therapy for myocardial infarction of rats.
abstract: OBJECTIVE
  Various methods are used to augment the efficacy of cell therapy in myocardial infarction (MI). In this study, we used the "activated platelet supernatant (APS)" to prime autologous "granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells ((mob) PBMCs)" and investigated the efficacy of cell-based therapy in MI.
  
  
  METHODS
  Rat (mob) PBMCs were isolated after daily subcutaneous injections of G-CSF at 100 μg/kg for 3 days. APS was isolated separately after activating rat platelets with thrombin 0.5 U/mL for 2 hours. Priming was performed with APS for 6 hours. To check the paracrine effect of primed (mob) PBMCs, we used the 36-hour culture supernatant of the primed cells. A rat MI model was used for an in vivo model.
  
  
  RESULTS
  Cytokines such as IL-1β, IL-10, and TGFβ were 3.7±0.9-fold, 3.4±1.2-fold, and 1.2±0.1-fold higher in APS, respectively, compared with naïve platelet supernatant. By APS priming, (mob) PBMCs showed M2 polarization and upregulation of angiogenic molecules (i.e., TEK, IL-10, CXCL1, and CX3CR1). APS-primed (mob) PBMCs had a 2.3-fold increased adhesion ability, induced by upregulated integrins. Rat endothelial cells cultured in the 36-hour culture supernatant of APS-primed (mob) PBMCs showed a 1.6-fold augmented proliferation and capillary network formation. In vivo transplantation of APS-primed (mob) PBMCs into rat MI models showed a significant trend of reduction in fibrosis area (P=.001) and wall thinning (P=.030), which lead to improvement in cardiac function measured by echocardiography.
  
  
  CONCLUSIONS
  Our data reveal that APS priming can enhance the wound-healing potential of (mob) PBMCs. APS priming may be a promising method for cell-based therapy of MI.
authors.affiliation: Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.|National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jeehoon
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.|National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.affiliation: National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.|National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Hak Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
authors.forename: Heewon
authors.initials: H
authors.lastname: Jung
authors.affiliation: National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Hwan
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.|National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.|Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.|Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D010641:Phenotype; D015539:Platelet Activation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing
chemical_list: D042501:Angiogenic Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor
keywords: Activated platelet supernatant; Cell Therapy; Cell priming; Granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells; M2 polarization; Myocardial infarction