Co-treating mesenchymal stem cells with IL‑1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function.
Inflammatory mediators are released by the myocardium following myocardial ischemia as a response to tissue injury, and contribute to cardiac repair and adaptive responses. Treating mesenchymal stem cells (MSCs) with various inflammatory factors activates a series of biological processes that enhance cell-mediated cardioprotection following myocardial infarction (MI). The present study was designed to examine the effect of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) treatment on vascular cell adhesion molecule-1 (VCAM-1) expression in MSCs, and to identify whether cytokine-treated MSCs improve post-ischemic myocardial function in a rat model. MSCs were stimulated with IL-1β and/or TNF-α for 24 h, the production of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion ability of MSCs were assessed by flow cytometry, adhesion assays, quantitative polymerase chain reaction and western blot analysis. The cardiac function was examined by two-dimensional echocardiography. The results demonstrated that in treated MSCs, the secretion of VCAM-1 and the cell adhesion ability were significantly increased, thus markedly improving cardiac function compared with that of the control group (P<0.01). Of all the groups, the rats stimulated with a combination of IL-1β and TNF-α exhibited the greatest cardiac improvements. However, there was no significant difference between the 10 and 20 ng/ml groups which were stimulated with one of the cytokines alone (P>0.05). In conclusion, stimulating MSCs with IL-1β and TNF-α promoted the expression of VCAM-1 and improved post-ischemic cardiac function recovery. Treating MSCs with two cytokines in combination may be a useful method to maximize the potential of cell-based therapy for MI.
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Chun-Miao
CM
Wang
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Zeng
Z
Guo
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Yang-Jing
YJ
Xie
Department of Emergency, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China.
Yu-Yu
YY
Hao
Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Ji-Min
JM
Sun
Department of Cardiology, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China.
Jian
J
Gu
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Ai-Ling
AL
Wang
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000503:physiopathology; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1