A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction
Authors: Saeed Yakhkeshi
Mohammad-Hossein Ghanian
Shima Tavakol
Sara Pahlavan
Elena Mahmoudi
Hossein Baharvand
Mansoureh Soleymani
Saman Firoozi
Shahram Rabbani
Maryam Barekat
Journal: Biomolecules (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: cardiac cell therapy; mesenchymal stem cells; myocardial infarction; self-assembling peptide hydrogel.
Affiliations: Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran., Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran., Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran., Research center for advanced technologies in cardiovascular medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran 1416753955, Iran., Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran 1449614535, Iran., Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran., Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Department of Developmental Biology, University of Science and Culture, ACECR, Tehran 1461968151, Iran.

Abstract:  Biomaterials in conjunction with stem cell therapy have recently attracted attention as a new therapeutic approach for myocardial infarction (MI), with the aim to solve the delivery challenges that exist with transplanted cells. Self-assembling peptide (SAP) hydrogels comprise a promising class of synthetic biomaterials with cardiac-compatible properties such as mild gelation, injectability, rehealing ability, and potential for sequence modification. Herein, we developed an SAP hydrogel composed of a self-assembling gel-forming core sequence (RADA) modified with SDKP motif with pro-angiogenic and anti-fibrotic activity to be used as a cardioprotective scaffold. The RADA-SDKP hydrogel was intramyocardially injected into the infarct border zone of a rat model of MI induced by left anterior descending artery (LAD) ligation as a cell-free or a cell-delivering scaffold for bone marrow mesenchymal stem cells (BM-MSCs). The left ventricular ejection fraction (LVEF) was markedly improved after transplantation of either free hydrogel or cell-laden hydrogel. This cardiac functional repair coincided very well with substantially lower fibrotic tissue formation, expanded microvasculature, and lower inflammatory response in the infarct area. Interestingly, BM-MSCs alone or in combination with hydrogel could not surpass the cardiac repair effects of the SDKP-modified SAP hydrogel. Taken together, we suggest that the RADA-SDKP hydrogel can be a promising cell-free construct that has the capability for functional restoration in the instances of acute myocardial infarction (AMI) that might minimize the safety concerns of cardiac cell therapy and facilitate clinical extrapolation. 

Retracted: No

PubPeer comments:
 Some figure panels in this paper appear to overlap with panels in another paper by the same research group, i.e. Saman Firoozi et al., Mesenchymal stem cell-derived extracellular vesicles alone or in conjunction with a SDKP-conjugated self-assembling peptide improve a rat model of myocardial infarction, Biochemical and Biophysical Research Communications 2020, DOI 10.1016 j.bbrc.2020.02.009, https: pubpeer.com publications 822065A8562E1384AE25D3D855644F Could the authors clarify if both papers used the same control animals? Even though some of the images and graphs of the  Vehicle group appear to look identical, other graphs appear to show different measurements. Here is a comparison of the heart sections and measurements in both papers: ![file] And here is a comparison of the angiogenesis microscopy images. Note here that the same image appears to have been used to represent the  Gel experiment in DOI: 10.3390 biom10020205 , and the  Gel + EV experiment in DOI: 10.1016 j.bbrc.2020.02.009. Also note that while the  Vehicle images are identical across both papers, the measured numbers of vessels appears to be different. ![file] , 
 From my understanding, the vehicle group is negative control group (If Ms Bik bother to read the paper and understand the experiment procedure), and the two animal studies may be conducted at the same time and used the same control group. That being said, Gel and Gel+EV group have similar figure, which is hard to explain. , 
 I did bother to read both papers, actually. As you can see in my comment #1, I was asking the authors if the same control animals were used in both papers. The reason I asked is because the bars reporting the numbers of the vesicles in the  Vehicle group appeared to be showing different values in the two papers (~10 in the Biomolecules paper, and ~7 in the jBBRC paper). And it is Dr. Bik for you. , 
 #1 Dear Dr. Bik, Thank you so much for your analysis of my articles! Currently, we are carefully checking each of your comments and concerns regarding  image concerns and undisclosed conflict of interest in some of my papers. We have also started to contact the related journals to ask for corrective notes on those articles that need correction or other potential actions. We will update, on Pubpeer, the final changes and actions communicated with the journals once we get feedback from the journals. Thank you again for your time and concern! Sincerely yours, Hossein Baharvand , 
 #1 Thank you for your concern. We have explained to the editor and asked to publish an Erratum to our manuscript to avoid any potential ambiguities in the future and they accepted. , 
 #5 Could you post an explanation and revised figures here please? ,