잠시만 기다려 주세요. 로딩중입니다.

Mesenchymal Stem Cell-Mediated Therapy of Peripheral Artery Disease Is Stimulated by a Lamin A-Progerin Binding Inhibitor

Journal of Lipid and Atherosclerosis 2020년 9권 3호 p.460 ~ 473
Heo Soon-Chul, Kwon Yang-Woo, 김규태, 권상모, 배선식, 박범준, 김재호,
소속 상세정보
 ( Heo Soon-Chul ) - Pusan National University School of Medicine Department of Physiology
 ( Kwon Yang-Woo ) - Pusan National University School of Medicine Department of Physiology
김규태 ( Park Gyu-Tae ) - Pusan National University School of Medicine Department of Physiology
권상모 ( Kwon Sang-Mo ) - Pusan National University School of Medicine Department of Physiology
배선식 ( Bae Sun-Sik ) - Pusan National University School of Medicine Department of Pharmacology
박범준 ( Park Bum-Joon ) - Pusan National University College of Natural Sciences Department of Molecular Biology
김재호 ( Kim Jae-Ho ) - Pusan National University School of Medicine Department of Physiology

Abstract


Objective: Human adipose tissue-derived mesenchymal stem cells (ASCs) have been reported to promote angiogenesis and tissue repair. However, poor survival and engraftment efficiency of transplanted ASCs are the major bottlenecks for therapeutic application. The present study aims to improve the therapeutic efficacy of ASCs for peripheral artery diseases.

Methods: Hydrogen peroxide (H2O2) was used to induce apoptotic cell death in ASCs. To measure apoptosis, we used flow cytometry-based apoptosis analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. A murine hindlimb ischemia model was established to measure the ASC-mediated therapeutic angiogenesis and in vivo survival ability of ASCs.

Results: We identified that the inhibitor of lamin A-progerin binding, JH4, protects ASCs against H2O2-induced oxidative stress and apoptosis. Co-administration of ASCs with JH4 improved ASC-mediated blood reperfusion recovery and limb salvage compared to that of the control group in a mouse hind limb ischemia model. Immunofluorescence showed that JH4 treatment potentiated ASC-mediated vascular regeneration via reducing ASC apoptosis post transplantation.

Conclusion: JH4 exerts anti-apoptotic effects in ASCs in conditions of oxidative stress, and contributes to the repair of ischemic hind limb injury by improving cell survival.

키워드

Mesenchymal stem cells; Apoptosis; Oxidative stress; Peripheral artery disease; Apoptosis

원문 및 링크아웃 정보

등재저널 정보