Left Ventricular Geometry and Angiogenesis Improvement in Rat Chronic Ischemic Cardiomyopathy following Injection of Encapsulated Mesenchymal Stem Cells

Document Type : Original Article


1 Tissue Engineering and Applied Cell Sciences Division, Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Rajaie Cardiovascular, Medical, and Research Center, Iran university of Medical Sciences, Tehran, Iran

3 Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

4 Biionix (Bionic Materials, Implants and Interfaces) Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, Florida, United States


Injection of hydrogel and cells into myocardial infarction (MI) patients is one of the emerging treatment
techniques, however, it has some limitations such as a lack of electromechanical properties and neovascularization.
We investigated the therapeutic potential of new electroactive hydrogel [reduced graphene oxide (rGO)/Alginate (ALG)]
encapsulated human bone marrow mesenchymal stem cells (BMSCs).

Materials and Methods
The experimental study involved ligating the left anterior descending coronary artery (LAD) in
rat models of chronic ischemic cardiomyopathy. Echocardiograms were analyzed at 4 and 8 weeks after MI treatment.
In the eighth week after injection in the heart, the rats were sacrificed. Histological and immunohistochemical analyses
were performed using Hematoxylin and Eosin (H&E) staining, Masson’s trichrome staining and anti-CD31 antibody to
analyze tissue structure and detect neovascularization.

In comparison to the control and other treatment groups, MSCs encapsulated in rGO-ALG showed significant
improvements in fractional shortening (FS), ejection fraction (EF), wall thickness and internal diameters (P<0.05). The
morphological observation showed several small blood vessels formed around the transplantation site in all treated
groups especially in the MSC-ALG-rGO group 8 weeks after the transplantation. Also, Masson’s trichrome staining
indicated an increased amount of collagen fibers in rGO-ALG-MSC. Microvessel density was significantly higher using
MSC-ALG-rGO compared to controls (P<0.01).

This study demonstrates that intramyocardial injection of rGO/ALG, a bio-electroactive hydrogel, is safe
for increasing LV function, neovascularization, and adjusting electrical characteristics following MI. The results confirm
ALG promising capability as a natural therapeutic for cardiac regeneration.


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