Evaluation of Multiple Biological Therapies for Ischemic Cardiac Disease
Authors: Francisco J Silva
Edward W Hsu
Courtney E Bartlett
Amalia A Winters
Alonso P Moreno
Donald L Atkinson
Hallie Thorp
Jose A Hawayek
Amit N Patel
David A Grainger
Sophia Bou-Ghannam
Journal: Cell Transplantation (2016)
Discipline: CLINICAL MEDICINE
Keywords: Regenerative medicine; Stem cells; Cardiac tissue repair; Myocardial infarction; Gene therapy
Affiliations: University of Utah School of Medicine, Salt Lake City, UT, USA., Department of Bioengineering, University of Utah, Salt Lake City, UT, USA, University of Utah School of Medicine, Salt Lake City, UT, USA, Nora Eccles Cardiovascular and Training Research Institute, Salt Lake City, UT, USA

Abstract:  The development of cell- and gene-based strategies for regenerative medicine offers a therapeutic option for the repair and potential regeneration of damaged cardiac tissue post-myocardial infarction (MI). Human umbilical cord subepithelial cell-derived stem cells (hUC-SECs), human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all derived from human tissue, have been shown to have in vitro and in vivo therapeutic potential. Additionally, S100a1, VEGF165, and stromal-derived factor-1α (SDF-1α) genes all have the potential to improve cardiac function and/or effect adverse remodeling. In this study, we compared the therapeutic potential of hBM-MSCs, hUC-SECs, and hiPSC-CMs along with plasmid-based genes to evaluate the in vivo potential of intramyocardially injected biologics to enhance cardiac function in a mouse MI model. Human cells derived from various tissue types were expanded under hypoxic conditions and injected intramyocardially into mice that had undergone left anterior descending (LAD) artery ligation. Similarly, plasmids were also injected into three groups of mice after LAD ligation. Seven experimental groups were studied in total: (1) control (saline), (2) hBM-MSCs, (3) hiPSC-CMs, (4) hUC-SECs, (5) S100a1 plasmid, (6) VEGF165 plasmid, and (7) SDF-1α plasmid. We evaluated echocardiography, hemodynamic catheterization measurements, and histology at 4 and 12 weeks post-biologic injection. Significant improvement was observed in cardiac function and contractility in hiPSC-CM and S100a1 groups and a significant reduction in left ventricle scar within the hUC-SEC group and a slight improvement in the SDF-1α and VEGF165 groups compared to the control group. These results demonstrate the potential for new biologic therapies to reduce scar burden and improve contractile function. 

Retracted: No

PubPeer comments:
 Table 1. Several rows of data are identical to each other. These values are highlighted below with boxes of the same color. ![file] Could the authors please clarify? There might be a perfectly good reason for these identical data, so I look forward to their reply. , 
 Table 3. Some values appear to be reported twice. Always in the same row or same column. Could the authors please check? ![file] , 
 Figure 3. * Blue boxes. The insets of F (hUC-SECs) and G (hiPSC-CMs) appear to look very similar. Could the authors please check? ![file] , 
 Figure 3 does appear similar but were verified to be different animals but roughly taken from that same place in the heart. However, the other cross sections that are shown are from different areas in each heart. As this is data from over 4 years ago, I have contacted each tech student to verify each group and await their response. , 
 October 6, 2020 u201cWinters, A. A., Bou-Ghannam, S., Thorp, H., Hawayek, J. A., Atkinson, D. L., Bartlett, C. E.,u2026Patel, A. N. (2016). Evaluation of Multiple Biological Therapies for Ischemic Cardiac Disease. Cell Transplantation, 1591u20131607. https: doi.org 10.3727 096368916X691501 In the above-referenced article, please find the correct versions of Tables 1 and 3 and Figure 3. Due to errors in copying and pasting data from the original datasets, certain rows were incorrect in Tables 1 3, and in panels G F in Figure 3. The online versions has been updated to reflect the correct information. The changes did not lead to substantive changes in the overall findings. The changes are not listed in full detail due to the limited significance. These errors do not affect the overall results of the study.u201c , 
 Images in Figure 3 (yellow boxes) appear to be the same. Based on [this article] , the corresponding author may no longer have access to the utah.edu address. Could one of the co-authors comment on the image similarities that he said he was investigating? *** ![file] ,