Co-treating mesenchymal stem cells with IL‑1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function

Wang,Chun-Miao; Guo,Zeng; Xie,Yang-Jing; Hao,Yu-Yu; Sun,Ji‑Min; Gu,Jian; Wang,Ai-Ling

doi:10.3892/mmr.2014.2236

Co-treating mesenchymal stem cells with IL‑1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function

Authors:
- Chun-Miao Wang
- Zeng Guo
- Yang-Jing Xie
- Yu-Yu Hao
- Ji‑Min Sun
- Jian Gu
- Ai-Ling Wang
View Affiliations

Affiliations: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Emergency, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Cardiology, The First People's Hospital of Hefei, Hefei, Anhui 230051, P.R. China
Published online on: May 13, 2014 https://doi.org/10.3892/mmr.2014.2236
Pages: 792-798

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Schulman IH and Hare JM: Key developments in stem cell therapy in cardiology. Regen Med. 7(6 Suppl): 17–24. 2012. View Article : Google Scholar
2	Luo Y, Wang Y, Poynter JA, et al: Pretreating mesenchymal stem cells with interleukin-1β and transforming growth factor-β synergistically increases vascular endothelial growth factor production and improves mesenchymal stem cell-mediated myocardial protection after acute ischemia. Surgery. 151:353–363. 2012.PubMed/NCBI
3	Zheng Z, Leng Y, Zhou C, Ma Z, Zhong Z, Shi XM and Zhang W: Effects of matrix metalloproteinase-1 on the myogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. Biochem Biophys Res Commun. 428:309–314. 2012. View Article : Google Scholar : PubMed/NCBI
4	Herrmann JL, Weil BR, Abarbanell AM, Wang Y, Poynter JA, Manukyan MC and Meldrum DR: IL-6 and TGF-α costimulate mesenchymal stem cell vascular endothelial growth factor production by ERK-, JNK-, and PI3K-mediated mechanisms. Shock. 35:512–516. 2011.
5	Cui X, Wang H, Guo H, Wang C, Ao H, Liu X and Tan YZ: Transplantation of mesenchymal stem cells preconditioned with diazoxide, a mitochondrial ATP-sensitive potassium channel opener, promotes repair of myocardial infarction in rats. Tohoku J Exp Med. 220:139–147. 2010. View Article : Google Scholar : PubMed/NCBI
6	Zhang M, Methot D, Poppa V, Fujio Y, Walsh K and Murry CE: Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol. 33:907–921. 2001. View Article : Google Scholar : PubMed/NCBI
7	Nian M, Lee P, Khaper N and Liu P: Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res. 94:1543–1553. 2004. View Article : Google Scholar : PubMed/NCBI
8	Carrero R, Cerrada I, Lledó E, et al: IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB. Stem Cell Rev. 8:905–916. 2012.
9	Fan H, Zhao G, Liu L, et al: Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis. Cell Mol Immunol. 9:473–481. 2012.
10	Heo SC, Jeon ES, Lee IH, Kim HS, Kim MB and Kim JH: Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms. J Invest Dermatol. 131:1559–1567. 2011.
11	Kim YS, Park HJ, Hong MH, et al: TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium. Front Biosci (Landmark Ed). 14:2845–2856. 2009. View Article : Google Scholar : PubMed/NCBI
12	Herrmann JL, Abarbanell AM, Weil BR, et al: Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-alpha improves acute myocardial function. Am J Physiol Regul Integr Comp Physiol. 299:R371–R378. 2010. View Article : Google Scholar
13	Deten A, Volz HC, Briest W and Zimmer HG: Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovasc Res. 55:329–340. 2002. View Article : Google Scholar : PubMed/NCBI
14	Chute JP: Stem cell homing. Curr Opin Hematol. 13:399–406. 2006. View Article : Google Scholar : PubMed/NCBI
15	Segers VF, Van Riet I, Andries LJ, et al: Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms. Am J Physiol Heart Circ Physiol. 290:H1370–H1377. 2006. View Article : Google Scholar : PubMed/NCBI
16	Balzer EM and Konstantopoulos K: Intercellular adhesion: mechanisms for growth and metastasis of epithelial cancers. Wiley Interdiscip Rev Syst Biol Med. 4:171–181. 2012. View Article : Google Scholar : PubMed/NCBI
17	Bonig H, Priestley GV and Papayannopoulou T: Hierarchy of molecular-pathway usage in bone marrow homing and its shift by cytokines. Blood. 107:79–86. 2006. View Article : Google Scholar : PubMed/NCBI
18	Hu Y, Cheng P, Xue YX and Liu YH: Glioma cells promote the expression of vascular cell adhesion molecule-1 on bone marrow-derived mesenchymal stem cells: a possible mechanism for their tropism toward gliomas. J Mol Neurosci. 48:127–135. 2012. View Article : Google Scholar : PubMed/NCBI
19	Wang Y, Crisostomo PR, Wang M, Markel TA, Novotny NM and Meldrum DR: TGF-alpha increases human mesenchymal stem cell-secreted VEGF by MEK- and PI3-K- but not JNK- or ERK-dependent mechanisms. Am J Physiol Regul Integr Comp Physiol. 295:R1115–R1123. 2008. View Article : Google Scholar : PubMed/NCBI
20	Herrmann JL, Abarbanell AM, Wang Y, Weil BR, Poynter JA, Manukyan MC and Meldrum DR: Transforming growth factor-α enhances stem cell-mediated postischemic myocardial protection. Ann Thorac Surg. 92:1719–1725. 2011.
21	Böcker W, Docheva D, Prall WC, et al: IKK-2 is required for TNF-alpha-induced invasion and proliferation of human mesenchymal stem cells. J Mol Med (Berl). 86:1183–1192. 2008.PubMed/NCBI
22	Tropel P, Noël D, Platet N, Legrand P, Benabid AL and Berger F: Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res. 295:395–406. 2004. View Article : Google Scholar : PubMed/NCBI
23	Wang A, Shen F, Lang Y and Wang J: Marrow-derived MSCs and atorvastatin improve cardiac function in rat model of AMI. Int J Cardiol. 150:28–32. 2011. View Article : Google Scholar : PubMed/NCBI
24	Ren G, Roberts AI and Shi Y: Adhesion molecules: key players in mesenchymal stem cell-mediated immunosuppression. Cell Adh Migr. 5:20–22. 2011. View Article : Google Scholar : PubMed/NCBI
25	Kim HJ, Lee SI, Lee DH, Smith D, Jo H, Schellhorn HE and Boo YC: Ascorbic acid synthesis due to L-gulono-1,4-lactone oxidase expression enhances NO production in endothelial cells. Biochem Biophys Res Commun. 345:1657–1662. 2006. View Article : Google Scholar : PubMed/NCBI
26	Niagara MI, Haider HKh, Jiang S and Ashraf M: Pharmacologically preconditioned skeletal myoblasts are resistant to oxidative stress and promote angiomyogenesis via release of paracrine factors in the infarcted heart. Circ Res. 100:545–555. 2007. View Article : Google Scholar
27	Mias C, Lairez O, Trouche E, et al: Mensenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiacventricular fibrosis after myocardial infarction. Stem Cells. 27:2734–2743. 2009. View Article : Google Scholar
28	Xiao Q, Wang SK, Tian H, et al: TNF-α increases bone marrow mesenchymal stem cell migration to ischemic tissues. Cell Biochem Biophys. 62:409–414. 2012.
29	Thankamony SP and Sackstein R: Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression primes transendothelial migration of human mesenchymal stem cells. Proc Natl Acad Sci USA. 108:2258–2263. 2011. View Article : Google Scholar
30	Hyun YM, Chung HL, McGrath JL, Waugh RE and Kim M: Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-1. J Immunol. 183:359–369. 2009. View Article : Google Scholar : PubMed/NCBI
31	Yilmaz G and Granger DN: Leukocyte recruitment and ischemic brain injury. Neuromolecular Med. 12:193–204. 2010. View Article : Google Scholar : PubMed/NCBI
32	Armiñán A, Gandía C, García-Verdugo JM, et al: Mesenchymal stem cells provide better results than hematopoietic precursors for the treatment of myocardial infarction. J Am Coll Cardiol. 55:2244–2253. 2010.PubMed/NCBI
33	Kawada H, Fujita J, Kinjo K, et al: Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood. 104:3581–3587. 2004. View Article : Google Scholar : PubMed/NCBI
34	Horwitz EM and Prather WR: Cytokines as the major mechanism of mesenchymal stem cell clinical activity: expanding the spectrum of cell therapy. Isr Med Assoc J. 11:209–211. 2009.PubMed/NCBI
35	Shake JG, Gruber PJ, Baumgartner WA, et al: Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg. 73:1919–1925. 2002. View Article : Google Scholar : PubMed/NCBI
36	Mangi AA, Noiseux N, Kong D, et al: Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 9:1195–1201. 2003. View Article : Google Scholar : PubMed/NCBI
37	Tsoyi K, Jang HJ, Nizamutdinova IT, et al: PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3β/GATA-6 signaling pathways in TNF-α-activated human endothelial cells. Atherosclerosis. 213:115–121. 2010.PubMed/NCBI
38	Ward SG, Westwick J and Harris S: Sat-Nav for T cells: role of PI3K isoforms and lipid phosphatases in migration of T lymphocytes. Immunol Lett. 138:15–18. 2011. View Article : Google Scholar : PubMed/NCBI