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Cardiovasc Ther. 2016;34(4):245-53.

Priming mobilized peripheral blood mononuclear cells with the "activated platelet supernatant" enhances the efficacy of cell therapy for myocardial infarction of rats.

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제1저자 강지훈,허진,강진아 · 교신저자 김효수

소속 (5)
  1. Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.
  2. National Research Laboratory for Stem Cell Niche, Seoul National University College of Medicine, Seoul, Korea.
  3. Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
  4. Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
  5. Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.

Abstract

AIM 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.

METHOD 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.

RESULT 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.

CONCLUSION 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.

© 2016 John Wiley & Sons Ltd.

Keywords

Activated platelet supernatantCell TherapyCell primingGranulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cellsM2 polarizationMyocardial infarction

그 밖의 정보
출판 형태
Journal Article
저널
Cardiovascular therapeutics · eISSN 1755-5922
MeSH
Angiogenic Proteins / metabolism · Animals · Blood Platelets / metabolism · Cell Adhesion Molecules / metabolism · Cell Proliferation · Cells, Cultured · Cytokines / blood · Disease Models, Animal · Endothelial Cells / metabolism · Granulocyte Colony-Stimulating Factor / administration & dosage · Injections, Subcutaneous · Leukocytes, Mononuclear / drug effects / metabolism / transplantation · Myocardial Infarction / blood / pathology / physiopathology / surgery · Neovascularization, Physiologic · Paracrine Communication* · Phenotype · Platelet Activation* · Rats, Sprague-Dawley · Recovery of Function · Subcellular Fractions / metabolism · Time Factors · Wound Healing
Substances
Angiogenic Proteins · Cell Adhesion Molecules · Cytokines · Granulocyte Colony-Stimulating Factor