Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction

Soon Jung Park; Ri Youn Kim; Bong Woo Park; Sunghun Lee; Seong Woo Choi; Jae Hyun Park; Jong Jin Choi; Seok Won Kim; Jinah Jang; Dong Woo Cho; Hyung Min Chung; Sung Hwan Moon; Kiwon Ban; Hun Jun Park

doi:10.1038/s41467-019-11091-2

Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction

Soon Jung Park, Ri Youn Kim, Bong Woo Park, Sunghun Lee, Seong Woo Choi, Jae Hyun Park, Jong Jin Choi, Seok Won Kim, Jinah Jang, Dong Woo Cho, Hyung Min Chung, Sung Hwan Moon, Kiwon Ban, Hun Jun Park

Division of Cardiology

Research output: Contribution to journal › Article › peer-review

179 Scopus citations

Abstract

Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.

Original language	English
Article number	3123
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11091-2
State	Published - 1 Dec 2019

Bibliographical note

Funding Information:
We would like to thank Mr. Joseph Seo at Konkuk University School of Medicine for instrumental discussions, directions and edits for this paper. This study was supported by CityU Research Project (9610355 to K.B.), the Hong Kong Research Grants Council (21100818 to K.B.), National Research Foundation of Korea grants (2015-M3A9C7030091, 2016R1C1B2015529 to S.H.M. and H.J.P., respectively), and the Bio & Medical Technology Development Program grant (NRF-2017M3A9B3061954 to H.J.P.) funded by the Ministry of Science & I.C.T. This study was also supported by the Technology Innovation Program funded (Grant No. 20000325 to S.H.M.) from the Ministry of Trade, Industry & Energy (MOTIE), Republic of Korea.

Publisher Copyright:
© 2019, The Author(s).

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Park, S. J., Kim, R. Y., Park, B. W., Lee, S., Choi, S. W., Park, J. H., Choi, J. J., Kim, S. W., Jang, J., Cho, D. W., Chung, H. M., Moon, S. H., Ban, K., & Park, H. J. (2019). Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction. Nature Communications, 10(1), Article 3123. https://doi.org/10.1038/s41467-019-11091-2

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abstract = "Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.",

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note = "Funding Information: We would like to thank Mr. Joseph Seo at Konkuk University School of Medicine for instrumental discussions, directions and edits for this paper. This study was supported by CityU Research Project (9610355 to K.B.), the Hong Kong Research Grants Council (21100818 to K.B.), National Research Foundation of Korea grants (2015-M3A9C7030091, 2016R1C1B2015529 to S.H.M. and H.J.P., respectively), and the Bio & Medical Technology Development Program grant (NRF-2017M3A9B3061954 to H.J.P.) funded by the Ministry of Science & I.C.T. This study was also supported by the Technology Innovation Program funded (Grant No. 20000325 to S.H.M.) from the Ministry of Trade, Industry & Energy (MOTIE), Republic of Korea. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction

Abstract

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