Priming mobilized peripheral blood mononuclear cells with the “activated platelet supernatant” enhances the efficacy of cell therapy for myocardial infarction of rats
Jeehoon Kang
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
These authors contributed equally to this work.Search for more papers by this authorJin Hur
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
These authors contributed equally to this work.Search for more papers by this authorJin-A Kang
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
These authors contributed equally to this work.Search for more papers by this authorHak Seung Lee
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
Search for more papers by this authorHeewon Jung
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
Search for more papers by this authorJae-Il Choi
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
Search for more papers by this authorHwan Lee
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
Search for more papers by this authorYong Sook Kim
Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
Search for more papers by this authorYoungkeun Ahn
Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
Search for more papers by this authorCorresponding Author
Hyo-Soo Kim
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
Correspondence
H.-S. Kim, M.D., Ph.D., Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, 101 DaeHak-ro, JongRo-gu, 110-744 Korea.
Email: [email protected]
Search for more papers by this authorJeehoon Kang
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
These authors contributed equally to this work.Search for more papers by this authorJin Hur
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
These authors contributed equally to this work.Search for more papers by this authorJin-A Kang
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
These authors contributed equally to this work.Search for more papers by this authorHak Seung Lee
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
Search for more papers by this authorHeewon Jung
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
Search for more papers by this authorJae-Il Choi
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
Search for more papers by this authorHwan Lee
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
Search for more papers by this authorYong Sook Kim
Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
Search for more papers by this authorYoungkeun Ahn
Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea
Search for more papers by this authorCorresponding Author
Hyo-Soo Kim
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
Correspondence
H.-S. Kim, M.D., Ph.D., Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, 101 DaeHak-ro, JongRo-gu, 110-744 Korea.
Email: [email protected]
Search for more papers by this authorSummary
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 (mobPBMCs)” and investigated the efficacy of cell-based therapy in MI.
Method
Rat mobPBMCs 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 mobPBMCs, 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, mobPBMCs showed M2 polarization and upregulation of angiogenic molecules (i.e., TEK, IL-10, CXCL1, and CX3CR1). APS-primed mobPBMCs 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 mobPBMCs showed a 1.6-fold augmented proliferation and capillary network formation. In vivo transplantation of APS-primed mobPBMCs 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 mobPBMCs. APS priming may be a promising method for cell-based therapy of MI.
Supporting Information
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