Asset Details
Do you wish to reserve the book?
Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
Do you wish to request the book?
Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
2019
Overview
Our previous studies showed that the combination of atorvastatin (ATV) and single injection of ATV‐pretreated mesenchymal stem cells (MSCs) (ATV‐MSCs) at 1 week post‐acute myocardial infarction (AMI) promoted MSC recruitment and survival. This study aimed to investigate whether the combinatorial therapy of intensive ATV with multiple injections of ATV‐MSCs has greater efficacy at different stages to better define the optimal strategy for MSC therapy in AMI. In order to determine the optimal time window for MSC treatment, we first assessed stromal cell‐derived factor‐1 (SDF‐1) dynamic expression and inflammation. Next, we compared MSC recruitment and differentiation, cardiac function, infarct size, and angiogenesis among animal groups with single, dual, and triple injections of ATV‐MSCs at early (Early1, Early2, Early3), mid‐term (Mid1, Mid2, Mid3), and late (Late1, Late2, Late3) stages. Compared with AMI control, intensive ATV significantly augmented SDF‐1 expression 1.5∼2.6‐fold in peri‐infarcted region with inhibited inflammation. ATV‐MSCs implantation with ATV administration further enhanced MSC recruitment rate by 3.9%∼24.0%, improved left ventricular ejection fraction (LVEF) by 2.0%∼16.2%, and reduced infarct size in all groups 6 weeks post‐AMI with most prominent improvement in mid groups and still effective in late groups. Mechanistically, ATV‐MSCs remarkably suppressed inflammation and apoptosis while increasing angiogenesis. Furthermore, triple injections of ATV‐MSCs were much more effective than single administration during early and mid‐term stages of AMI with the best effects in Mid3 group. We conclude that the optimal strategy is multiple injections of ATV‐MSCs combined with intensive ATV administration at mid‐term stage of AMI. The translational potential of this strategy is clinically promising. Stem Cells Translational Medicine 2019;8:1068–1083 Our study first revealed that intensive atorvastatin (ATV) treatment dramatically augmented the SDF‐1 expression in peri‐infarcted myocardium over the entire period of AMI with simultaneous inhibiting the inflammation. The optimal strategy for further improving the efficacy of mesenchymal stem cells (MSCs) therapy was at least triple intravenous administrations of ATV‐pretreated MSCs in mid‐term stage of AMI combined with intensive ATV treatment. The underlying mechanisms mainly attributed to the marked enhancement of ATV‐MSCs recruitment and survival, angiogenesis in the infarcted region instead of myocardium regeneration.
Publisher
John Wiley & Sons, Inc,Oxford University Press
