514 438

Cited 75 times in

Mesenchymal stem cells pretreated with delivered Hph-1-Hsp70 protein are protected from hypoxia-mediated cell death and rescue heart functions from myocardial injury

Authors
 WOOCHUL CHANG  ;  BYEONG-WOOK SONG  ;  SOYEON LIM  ;  HEESANG SONG  ;  CHI YOUNG SHIM  ;  MIN-JI CHA  ;  DONG HYUCK AHN  ;  YOUNG-GOOK JUNG  ;  DONG-HO LEE  ;  JI HYUNG CHUNG  ;  KI-DOO CHOI  ;  SEUNG-KYOU LEE  ;  NAMSIK CHUNG  ;  SANG-KYOU LEE  ;  YANGSOO JANG  ;  KI-CHUL HWANG 
Citation
 STEM CELLS, Vol.27(9) : 2283-2292, 2009 
Journal Title
 STEM CELLS 
ISSN
 1066-5099 
Issue Date
2009
MeSH
Adenosine Triphosphate/metabolism ; Animals ; Carrier Proteins/genetics* ; Caspase 3/metabolism ; Cell Death/genetics ; Cell Death/physiology* ; Cell Hypoxia/genetics ; Cell Hypoxia/physiology* ; Cell Survival/genetics ; Cell Survival/physiology ; Cells, Cultured ; HSP70 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/physiology* ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stromal Cells/cytology* ; Mesenchymal Stromal Cells/metabolism* ; Myocardial Infarction/therapy* ; Polycomb Repressive Complex 1 ; Rats ; Rats, Sprague-Dawley
Keywords
Mesenchymal stem cells ; Protein transduction domains ; Myocardial infarction
Abstract
Mesenchymal stem cell (MSC) therapy for myocardial injury has inherent limitations due to the poor viability of MSCs after cell transplantation. In this study, we directly delivered Hsp70, a protein with protective functions against stress, into MSCs, using the Hph-1 protein transduction domain ex vivo for high transfection efficiency and low cytotoxicity. Compared to control MSCs in in vitro hypoxic conditions, MSCs delivered with Hph-1-Hsp70 (Hph-1-Hsp70-MSCs) displayed higher viability and anti-apoptotic properties, including Bcl2 increase, reduction of Bax, JNK phosphorylation and caspase-3 activity. Hsp70 delivery also attenuated cellular ATP-depleting stress. Eight animals per group were used for in vivo experiments after occlusion of the left coronary artery. Transplantation of Hph-1-Hsp70-MSCs led to a decrease in the fibrotic heart area, and significantly reduced the apoptotic positive index by 19.5 +/- 2%, compared to no-treatment controls. Hph-1-Hsp70-MSCs were well-integrated into the infarcted host myocardium. The mean microvessel count per field in the infarcted myocardium of the Hph-1-Hsp70-MSC-treated group (122.1 +/- 13.5) increased relative to the MSC-treated group (75.9 +/- 10.4). By echocardiography, transplantation of Hph-1-Hsp70-MSCs resulted in additional increases in heart function, compared to the MSCs-transplanted group. Our results may help formulate better clinical strategies for in vivo MSC cell therapy for myocardial damage.
Files in This Item:
T200903417.pdf Download
DOI
10.1002/stem.153
Appears in Collections:
5. Research Institutes (연구소) > Cardiovascular Product Evaluation Center (심혈관제품유효성평가센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Song, Byeong Wook(송병욱)
Shim, Chi Young(심지영) ORCID logo https://orcid.org/0000-0002-6136-0136
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Chung, Nam Sik(정남식)
Chung, Ji Hyung(정지형)
Cha, Min Ji(차민지)
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105014
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse