Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction

Abstract 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 combinat...

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Autores principales:	Jun Xu, Yu‐Yan Xiong, Qing Li, Meng‐Jin Hu, Pei‐Sen Huang, Jun‐Yan Xu, Xia‐Qiu Tian, Chen Jin, Jian‐Dong Liu, Li Qian, Yue‐Jin Yang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2019
Materias:	Mesenchymal stem cells Atorvastatin Timing Multiple administrations Acute myocardial infarction Medicine (General) R5-920 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/57d7d78e30a040a482f09c50611cba82
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spelling	oai:doaj.org-article:57d7d78e30a040a482f09c50611cba822021-11-30T19:15:37ZOptimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction2157-65802157-656410.1002/sctm.19-0013https://doaj.org/article/57d7d78e30a040a482f09c50611cba822019-10-01T00:00:00Zhttps://doi.org/10.1002/sctm.19-0013https://doaj.org/toc/2157-6564https://doaj.org/toc/2157-6580Abstract 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;8:1068–1083Jun XuYu‐Yan XiongQing LiMeng‐Jin HuPei‐Sen HuangJun‐Yan XuXia‐Qiu TianChen JinJian‐Dong LiuLi QianYue‐Jin YangWileyarticleMesenchymal stem cellsAtorvastatinTimingMultiple administrationsAcute myocardial infarctionMedicine (General)R5-920CytologyQH573-671ENStem Cells Translational Medicine, Vol 8, Iss 10, Pp 1068-1083 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mesenchymal stem cells Atorvastatin Timing Multiple administrations Acute myocardial infarction Medicine (General) R5-920 Cytology QH573-671
spellingShingle	Mesenchymal stem cells Atorvastatin Timing Multiple administrations Acute myocardial infarction Medicine (General) R5-920 Cytology QH573-671 Jun Xu Yu‐Yan Xiong Qing Li Meng‐Jin Hu Pei‐Sen Huang Jun‐Yan Xu Xia‐Qiu Tian Chen Jin Jian‐Dong Liu Li Qian Yue‐Jin Yang Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
description	Abstract 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
format	article
author	Jun Xu Yu‐Yan Xiong Qing Li Meng‐Jin Hu Pei‐Sen Huang Jun‐Yan Xu Xia‐Qiu Tian Chen Jin Jian‐Dong Liu Li Qian Yue‐Jin Yang
author_facet	Jun Xu Yu‐Yan Xiong Qing Li Meng‐Jin Hu Pei‐Sen Huang Jun‐Yan Xu Xia‐Qiu Tian Chen Jin Jian‐Dong Liu Li Qian Yue‐Jin Yang
author_sort	Jun Xu
title	Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
title_short	Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
title_full	Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
title_fullStr	Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
title_full_unstemmed	Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction
title_sort	optimization of timing and times for administration of atorvastatin‐pretreated mesenchymal stem cells in a preclinical model of acute myocardial infarction
publisher	Wiley
publishDate	2019
url	https://doaj.org/article/57d7d78e30a040a482f09c50611cba82
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Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction

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