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Xu et al. Vessel Plus 2023;7:33 Vessel Plus
DOI: 10.20517/2574-1209.2023.98

Original Article Open Access

Lack of cardiac benefit after intramyocardial or

intravenous injection of mesenchymal stem cell-
derived extracellular vesicles supports the need for

optimized cardiac delivery

1,2
1,2
1,2
2
Cynthia M. Xu , Mark Broadwin 1,2 , Patrick Faherty , Rayane Brinck Teixeira , Mohamed Sabra , Frank
1,2
W. Sellke , M. Ruhul Abid 1,2
1
Cardiovascular Research Center, Rhode Island Hospital, Providence, RI 02903, USA.
2
Division of Cardiothoracic Surgery Alpert Medical School of Brown University and Rhode Island Hospital Providence,
Providence, RI 02903, USA.
Correspondence to: Dr. M. Ruhul Abid, Cardiovascular Research Center, Rhode Island Hospital, Coro West, 5.231, 1 Hoppin
Street, Providence, RI 02903, USA. E-mail: ruhul_abid@brown.edu
How to cite this article: Xu CM, Broadwin M, Faherty P, Teixeira RB, Sabra M, Sellke FW, Abid MR. Lack of cardiac benefit after
intramyocardial or intravenous injection of mesenchymal stem cell-derived extracellular vesicles supports the need for optimized
cardiac delivery. Vessel Plus 2023;7:33. https://dx.doi.org/10.20517/2574-1209.2023.98

Received: 1 Aug 2023 First Decision: 12 Oct 2023 Revised: 28 Nov 2023 Accepted: 13 Dec 2023 Published: 22 Dec 2023
Academic Editor: Manel SabatéCopy Editor: Fangyuan Liu Production Editor: Fangyuan Liu

Abstract
Aim: To determine the differences in improvement in cardiac function by intramyocardial (IM) vs. intravenous (IV)
injection of human bone mesenchymal stem cell-derived extracellular vesicles (HBMSC-EV) after acute MI.

Methods: FVB mice underwent acute MI via left anterior descending coronary artery ligation and subsequent
injection of: (1) IM saline control; (2) IM HBMSC-EV; (3) IV saline control; and (4) IV HBMSC-EV. Cardiac function
was evaluated with weekly postoperative echocardiography. On postoperative day 28, the mice were euthanized,
and the heart, lungs, liver, spleen, and kidneys were harvested. Given previous studies showing HBMSC-EV hepatic
uptake after IV injection, the liver was evaluated for changes in inflammation, fibrosis, and proliferation.

Results: On postoperative day 28, there were no significant differences in left ventricular ejection fraction
(P = 0.6151), fractional shortening (P = 0.1135), or anterior border zone fibrosis (P = 0.6333) in any of the
experimental groups. Interestingly, there was a strong trend demonstrating improvement in infarct size on fibrosis
staining, which did not reach significance (P = 0.05620). There were no differences in hepatic inflammation,
fibrosis, and proliferation.

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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