Hongliang Liang, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, the Fourth Military Medical University, No.127, West Changle Road, Xi'an, Shaanxi Province 710032, China
Huiyuan Hou, Eye Institute of Chinese PLA, Xijing Hospital, the Fourth Military Medical University, Xi'an, China
Wei Yi, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, the Fourth Military Medical University, No.127, West Changle Road, Xi'an, Shaanxi Province 710032, ChinaFollow
Guodong Yang, The State Key laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, China
Chunhu Gu, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, the Fourth Military Medical University, No.127, West Changle Road, Xi'an, Shaanxi Province 710032, China
Wayne Bond Lau, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Erhe Gao, Thomas Jefferson UniversityFollow
Xinliang Ma, Thomas Jefferson UniversityFollow
Zifan Lu, The State Key laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, China
Xufeng Wei, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, the Fourth Military Medical University, No.127, West Changle Road, Xi'an, Shaanxi Province 710032, ChinaFollow
Jianming Pei, Department of Physiology, the Fourth Military Medical University, Xi'an, China
Dinghua Yi, Institute of Cardiovascular Disease of Chinese PLA, Xijing Hospital, the Fourth Military Medical University, No.127, West Changle Road, Xi'an, Shaanxi Province 710032, ChinaFollow

Document Type

Article

Publication Date

6-1-2013

Comments

This article has been peer reviewed. It was published in European Health Journal.

Volume 34, Issue 22, June 2013, Pages 1681-90.

The published version is available at DOI: 10.1093/eurheartj/ehr131. Copyright © Oxford University Press.

Abstract

AIMS: Mesenchymal stem cells (MSCs) can ameliorate myocardial infarction (MI) injury. However, older-donor MSCs seem less efficacious than those from younger donors, and the contributing underlying mechanisms remain unknown. Here, we determine how age-related expression of pigment epithelium-derived factor (PEDF) affects MSC therapeutic efficacy for MI.

METHODS AND RESULTS: Reverse transcriptase-polymerized chain reaction and enzyme-linked immunosorbent assay analyses revealed dramatically increased PEDF expression in MSCs from old mice compared to young mice. Morphological and functional experiments demonstrated significantly impaired old MSC therapeutic efficacy compared with young MSCs in treatment of mice subjected to MI. Immunofluorescent staining demonstrated that administration of old MSCs compared with young MSCs resulted in an infarct region containing fewer endothelial cells, vascular smooth muscle cells, and macrophages, but more fibroblasts. Pigment epithelium-derived factor overexpression in young MSCs impaired the beneficial effects against MI injury, and induced cellular profile changes in the infarct region similar to administration of old MSCs. Knocking down PEDF expression in old MSCs improved MSC therapeutic efficacy, and induced a cellular profile similar to young MSCs administration. Studies in vitro showed that PEDF secreted by MSCs regulated the proliferation and migration of cardiac fibroblasts.

CONCLUSIONS: This is the first evidence that paracrine factor PEDF plays critical role in the regulatory effects of MSCs against MI injury. Furthermore, the impaired therapeutic ability of aged MSCs is predominantly caused by increased PEDF secretion. These findings indicate PEDF as a promising novel genetic modification target for improving aged MSC therapeutic efficacy.

PubMed ID

21606086

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