scholarly journals Dodging COVID-19 infection: Low expression and localization of Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in Mesenchymal Stem Cells derived from human umbilical cord (hUC-MSCs). 

2020 ◽  
Author(s):  
Jonathan J Hernandez ◽  
Doyle E Beaty ◽  
Logan L Fruhwirth ◽  
J M Sloan ◽  
Ana P Lopez Chaves ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Mesenchymal Stem Cells ◽  
Angiotensin Converting Enzyme ◽  
Western Blot ◽  
Human Umbilical Cord ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Transmembrane Serine Protease ◽  
Low Expression

Abstract Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al. recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). In this report, the expression of ACE2 and TMPRSS2 was analyzed in 24 lots of hUC-MSCs derived from 24 different donors via quantitative polymerase chain reaction (qPCR), Western Blot, immunofluorescence and flow cytometry. hUC-MSCs had significantly lower ACE2 (p=0.002) and TMPRSS2 (p=0.008) expression compared with human lung tissue homogenates in Western blot analyses. Little to no expression of ACE2 or TMPRSS2 was observed in hUC-MSC by qPCR, and they were not observable with immunofluorescence in hUC-MSCs cell membranes. A double negative ACE2 and TMPRSS2 population percentage of 94.30% ±15.55 was obtained for hUC-MSCs via flow cytometry, with only 0.011% ACE2 and 10.91% TMPRSS2 observable positive populations. We have demonstrated negative expression of ACE2 and low expression of TMPRSS2 in 24 lots of hUC-MSCs. This has crucial implications for the design of future therapeutic options for COVID-19, since hUC-MSCs would have the ability to “dodge” viral infection to exert their immunomodulatory effects.

scholarly journals Dodging COVID-19 infection: low expression and localization of ACE2 and TMPRSS2 in multiple donor-derived lines of human umbilical cord-derived mesenchymal stem cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jonathan J. Hernandez ◽  
Doyle E. Beaty ◽  
Logan L. Fruhwirth ◽  
Ana P. Lopes Chaves ◽  
Neil H. Riordan
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Viral Infection ◽  
Umbilical Cord ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Umbilical Cord ◽  
Human Lung Tissue ◽  
Low Expression

Abstract Background Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al. recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). The purpose of this study was to quantify the expression of ACE2 and TMPRSS2 in hUC-MSCs lots derived from multiple donors using molecular-based techniques in order to demonstrate their inability to be a host to SARS-CoV-2. Methods Expression of ACE2 and TMPRSS2 was analyzed in 24 lots of hUC-MSCs derived from Wharton's jelly via quantitative polymerase chain reaction (qPCR), Western Blot, immunofluorescence and flow cytometry using 24 different donors. Results hUC-MSCs had significantly lower ACE2 (p = 0.002) and TMPRSS2 (p = 0.008) expression compared with human lung tissue homogenates in Western blot analyses. Little to no expression of ACE2 was observed in hUC-MSC by qPCR, and they were not observable with immunofluorescence in hUC-MSCs cell membranes. A negative ACE2 and TMPRSS2 population percentage of 95.3% ± 15.55 was obtained for hUC-MSCs via flow cytometry, with only 4.6% ACE2 and 29.5% TMPRSS2 observable positive populations. Conclusions We have demonstrated negative expression of ACE2 and low expression of TMPRSS2 in 24 lots of hUC-MSCs. This has crucial implications for the design of future therapeutic options for COVID-19, since hUC-MSCs would have the ability to “dodge” viral infection to exert their immunomodulatory effects.

scholarly journals Mesenchymal stem cells with overexpression of Angiotensin-converting enzyme-2 improved the microenvironment and cardiac function in a rat model of myocardial infarction

2020 ◽  
Author(s):  
Chao Liu ◽  
Yue Fan ◽  
Hong-Yi Zhu ◽  
Lu zhou ◽  
Yu Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Angiotensin Converting Enzyme ◽  
Cardiac Function ◽  
Heart Function ◽  
Tube Formation ◽  
Border Zone ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

AbstractBackgroundAngiotensin-converting enzyme-2 (ACE2) overexpression improves left ventricular remodeling and function in diabetic cardiomyopathy; however, the effect of ACE2-overexpressed mesenchymal stem cells (MSCs) on myocardial infarction (MI) remains unexplored. This study aimed to investigate the effect of ACE2-overexpression on the function of MSCs and the therapeutic efficacy of MSCs for MI.MethodsMSCs were transfected with Ace2 gene using lentivirus, and then transplanted into the border zone of ischemic heart. The renin-angiotensin system (RAS) expression, nitric oxide synthase (NOS) expression, paracrine factors, anti-hypoxia ability, tube formation of MSCs, and heart function were determined.ResultsMSCs expressed little ACE2. ACE2-overexpression decreased the expression of AT1 and VEGF apparently, up-regulated the paracrine of HGF, and increased the synthesis of Angiotensin 1-7 in vitro. ACE2-overexpressed MSCs showed a cytoprotective effect on cardiomyocyte, and an interesting tube formation ability, decreased the heart fibrosis and infarct size, and improved the heart function.ConclusionTherapies employing MSCs with ACE2 overexpression may represent an effective treatment for improving the myocardium microenvironment and the cardiac function after MI.

Abstract TP102: Human Placental Mesenchymal Stem Cells Derived Exosome-Angiotensin Converting Enzyme-2 Dependent Protection in Ischemic Stroke Injury

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mansoureh Barzegar ◽  
Yuping Wang ◽  
Jungmi W. Yun ◽  
Oleg Chernyshev ◽  
Roger Kelley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Flow ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Angiotensin Converting Enzyme ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Placental Mesenchymal Stem Cells

Following thrombolytic therapy for stroke, ischemia/reperfusion (I/R) mediated inflammation often disrupts the blood brain barrier (BBB). This can enhance expression of endothelial adhesion markers and perturb normal blood flow regulation. Proposed benefits of stem cell therapy (SCT) in stroke, besides long-term trans-differentiation into neural cells, include secretion of protective factors, which partly depends on exosomes released by stem cells. We evaluated human placenta mesenchymal stem cells (hPMSC) as potential ameliorative SCT in an acute ischemic stroke model. We hypothesize that hPMSC would achieve site-specific suppression of post-ischemic immune cell transmigration, preservation of the BBB and maintenance of blood flow via ‘paracrine’ signaling pathways in acute stroke injury.We found that intraperitoneal (IP) administration of hPMSC at the time of reperfusion, using the middle cerebral artery occlusion (MCAO)/reperfusion model, produced significant protection ( p =0.0001) of the ipsilateral hemisphere. We also demonstrated that hPMSC-treated MCAO mice exhibited significantly greater neurological recovery ( p <0.0001) compared to untreated MCAO, an effect which was accompanied by significant restoration of blood flow ( p <0.01) to the MCAO-stressed brains. Using Evans Blue dye assay, we also observed significant ( p =0.004) improvement of BBB integrity in ipsilateral hemispheres of hPMSC-treated mice vs MCAO controls. Furthermore, we determined that hPMSC-derived exosomes contribute to paracrine based protection of hPMSC in MCAO model. Importantly, we found that hPMSC/exosome protection is mediated partly by the function of angiotensin converting enzyme 2 (ACE2). To evaluate the contribution of ACE2 in protection of the brain after ischemic stroke, we first demonstrated that hPMSC and their exosomes express ACE2. Second, mice injected with hPMSC which had been pre-treated with the specific ACE2 inhibitor (10μM) MLN-4760, showed tissue injury and neurological behavior similar to that seen in untreated MCAO.We conclude that pleiotropic factors associated with hPMSC administration can have a favorable impact on blood flow, BBB integrity potentially alleviating the detrimental effects of ischemic stroke.

scholarly journals Dodging COVID-19 Infection: Low Expression and Localization of ACE2 and TMPRSS2 in Human Umbilical Cord-Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Jonathan J Hernandez ◽  
Doyle E Beaty ◽  
Logan L Fruhwirth ◽  
Ana P Lopes Chaves ◽  
Neil H Riordan
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Western Blot ◽  
Viral Infection ◽  
Umbilical Cord ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Umbilical Cord ◽  
Human Lung Tissue ◽  
Novel Coronavirus ◽  
Low Expression

Abstract BackgroundMesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al. recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). MethodsExpression of ACE2 and TMPRSS2 was analyzed in 24 lots of hUC-MSCs derived fromWharton's jelly via quantitative polymerase chain reaction (qPCR), Western Blot, immunofluorescence and flow cytometry using 24 different donors. ResultshUC-MSCs had significantly lower ACE2 (p=0.002) and TMPRSS2 (p=0.008) expression compared with human lung tissue homogenates in Western blot analyses. Little to no expression of ACE2 was observed in hUC-MSC by qPCR, and they were not observable with immunofluorescence in hUC-MSCs cell membranes. A negative ACE2 and TMPRSS2 population percentage of 95.3% ±15.55 was obtained for hUC-MSCs via flow cytometry, with only 4.6% ACE2 and 29.5% TMPRSS2 observable positive populations. ConclusionsWe have demonstrated negative expression of ACE2 and low expression of TMPRSS2 in 24 lots of hUC-MSCs. This has crucial implications for the design of future therapeutic options for COVID-19, since hUC-MSCs would have the ability to “dodge” viral infection to exert their immunomodulatory effects.

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