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Effect of intravenous cell therapy in rats with old myocardial infarction

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Abstract

Mounting evidence shows that cell therapy provides therapeutic benefits in experimental and clinical settings of chronic heart failure. However, direct cardiac delivery of cells via transendocardial injection is logistically complex, expensive, entails risks, and is not amenable to multiple dosing. Intravenous administration would be a more convenient and clinically applicable route for cell therapy. Thus, we determined whether intravenous infusion of three widely used cell types improves left ventricular (LV) function and structure and compared their efficacy. Rats with a 30-day-old myocardial infarction (MI) received intravenous infusion of vehicle (PBS) or 1 of 3 types of cells: bone marrow mesenchymal stromal cells (MSCs), cardiac mesenchymal cells (CMCs), and c-kit-positive cardiac cells (CPCs), at a dose of 12 × 106 cells. Rats were followed for 35 days after treatment to determine LV functional status by serial echocardiography and hemodynamic studies. Blood samples were collected for Hemavet analysis to determine inflammatory cell profile. LV ejection fraction (EF) dropped ≥ 20 points in all hearts at 30 days after MI and deteriorated further at 35-day follow-up in the vehicle-treated group. In contrast, deterioration of EF was halted in rats that received MSCs and attenuated in those that received CMCs or CPCs. None of the 3 types of cells significantly altered scar size, myocardial content of collagen or CD45-positive cells, or Hemavet profile. This study demonstrates that a single intravenous administration of 3 types of cells in rats with chronic ischemic cardiomyopathy is effective in attenuating the progressive deterioration in LV function. The extent of LV functional improvement was greatest with CPCs, intermediate with CMCs, and least with MSCs.

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Acknowledgements

This study was supported in part by NIH Grants HL113530 and HL-078825.

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  1. Xian-Liang Tang and Marcin Wysoczynski have contributed equally as first authors.

Authors and Affiliations

  1. Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA

    Xian-Liang Tang, Marcin Wysoczynski, Anna M. Gumpert, Yan Li, Wen-Jian Wu, Hong Li, Heather Stowers & Roberto Bolli

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  1. Xian-Liang Tang
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  2. Marcin Wysoczynski
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  6. Hong Li
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Contributions

Conceptualization: RB; Study design: X-LT and MW; Material preparation, data collection, and analysis: X-LT, MW, AMG, YL, W-JW, HL, and HS. The first draft of the manuscript was written by X-LT and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Roberto Bolli.

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Tang, XL., Wysoczynski, M., Gumpert, A.M. et al. Effect of intravenous cell therapy in rats with old myocardial infarction. Mol Cell Biochem 477, 431–444 (2022). https://doi.org/10.1007/s11010-021-04283-2

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