Exosomes derived from adipose tissue, bone marrow, and umbilical cord blood for cardioprotection after myocardial infarction
Authors: Zhongchao Wang
Baoxia Zhang
Longmei Liu
Huiyu Xu
Bao Li
Journal: Journal of Cellular Biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: adipose tissue-derived mesenchymal stem cell; bone marrow mesenchymal stem cell; exosome; myocardial infarction; umbilical cord blood-derived mesenchymal stem cell.
Affiliations: Shanxi Medical University Taiyuan Shanxi China, Department of CardiologyShanxi Cardiovascular Hospital Taiyuan Shanxi China, Department of Cardiovascular laboratoryShanxi Cardiovascular Hospital Taiyuan Shanxi China

Abstract:  Human mesenchymal stem cells (MSCs) have the potential for improving cardiac function following myocardial infarction (MI). This study was performed to explore the cardioprotection of bone marrow mesenchymal stem cells (BMMSCs), adipose tissue-derived mesenchymal stem cells (ADMSCs), and umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) for myocardium in rats after MI. MI models were established in rats, which were injected with PBS, BMMSCs, ADMSCs, and UCMSCs. Cardiac function was detected by ultrasonic cardiogram. TTC staining, TUNEL staining, and immunohistochemistry were adopted to determine infarction area, cardiomyocyte apoptosis, and microvascular density (MVD), respectively. Exosomes were derived from BMMSCs, ADMSCs, and UCBMSCs, and identified by morphological observation and CD63 expression detection. Neonatal rat cardiomyocytes (NRCMs) were isolated and cultured with hypoxia, subjected to PBS and exosomes derived from BMMSCs, ADMSCs, and UCMSCs. Flow cytometry and enzyme-linked immunosorbent assay were used to determine NRCM apoptosis and the levels of angiogenesis-related markers (VEGF, bFGF, and HGF). According to ultrasonic cardiogram, BMMSCs, ADMSCs, and UCMSCs facilitated the cardiac function of MI rats. Furthermore, three kinds of MSCs inhibited cardiomyocyte apoptosis, infarction area, and increased MVD. NRCMs treated with exosomes derived from BMMSCs, ADMSCs, and UCMSCs reduced the NRCM apoptosis and promoted angiogenesis by increasing levels of VEGF, bFGF, and HGF. Notably, exosomes from ADMSCs had the most significant effect. On the basis of the results obtained from this study, exosomes derived from BMMSCs, ADMSCs, and UCBMSCs inhibited the cardiomyocyte apoptosis and promoted angiogenesis, thereby improving cardiac function and protecting myocardium. Notably, exosomes from ADMSCs stimulated most of the cardioprotection factors. 

Retracted: No

PubPeer comments:
 Fig 4 B-G.  BMMSCs, ADMSCs, and UCMSCs in addition to their exosomes conferred cardioprotection in rats with MI, n = 10.... B, HE staining to observe pathological changes of myocardial tissues (u00d7200); C, TUNEL staining to evaluate cardiomyocyte apoptosis (u00d7400); D, the apoptosis rate of cardiomyocytes of MI rats among different groups; **E, TTC staining for the infarction of rats**; F, the infarction area of MI rats among different groups; G, immunohistochemical analysis for microvascular density ![file] Two panels of G overlap at the corners after a 180-deg flip. Of more concern, perhaps, is that a row of images of **brain slices** is illustrating some purported findings for **heart injury**. , 
 Kind of a nit-picky thing compared with confusing brain with heart, but the  exosome preparation was simply a 50 kDa retentate. Yes, there will be extracellular vesicles there, but this method is not specific to EVs much less exosomes. Any effects of this fraction were likely due to free proteins that were concentrated along with EVs and who knows what else. Yet another  exosome paper that s not... , 
 #2 Then there are these two panels from 4B. ![file] When two purportedly HE-stained slides overlap except for the part where one has an enclave of cells that s not present in the other, it kind of undermines one s faith in the reality of any of the reported results. ,