Promigratory Activity of Oxytocin on Umbilical Cord Blood-Derived Mesenchymal Stem Cells
Yong Sook Kim
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorJin Sook Kwon
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorMoon Hwa Hong
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorChang Hun Song
JB Stem Cell Institute, Inc., Gwangju, South Korea
Search for more papers by this authorMyung Ho Jeong
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorCorresponding Author
Youngkeun Ahn
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Prof. Youngkeun Ahn, Heart Center of Chonnam National University Hospital, 8 Hak Dong, Dong Ku, Gwangju 501-757, South Korea. E-mail: [email protected]Search for more papers by this authorYong Sook Kim
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorJin Sook Kwon
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorMoon Hwa Hong
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorChang Hun Song
JB Stem Cell Institute, Inc., Gwangju, South Korea
Search for more papers by this authorMyung Ho Jeong
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Search for more papers by this authorCorresponding Author
Youngkeun Ahn
The Heart Center and
Heart Research Center of Chonnam National University Hospital; and
Prof. Youngkeun Ahn, Heart Center of Chonnam National University Hospital, 8 Hak Dong, Dong Ku, Gwangju 501-757, South Korea. E-mail: [email protected]Search for more papers by this authorAbstract
Recent studies show that oxytocin has various effects on cellular behaviors. Oxytocin is reported to stimulate cardiomyogenesis of embryonic stem cells and endothelial cell proliferation. Mesenchymal stem cells (MSCs) are widely used for cardiac repair, and we elucidated the effect of oxytocin on umbilical cord derived-MSCs (UCB-MSCs). UCB-MSCs were pretreated with oxytocin (100 nM) and washed with saline prior to experiments. To evaluate their angiogenic potential and migration activity, tube formation assay and Boyden chamber assay were performed. For in vivo study, ischemia-reperfusion was induced in rats, and UCB-MSCs with or without oxytocin pretreatment were injected into the infarcted myocardium to evaluate the engraftment of injected cells. Histological and hemodynamic studies were performed. Oxytocin-treated UCB-MSCs showed a decrease in tube formation but a drastic increase in transwell migration activity. The transcription level of matrix metalloproteinase (MMP)-2 was increased in oxytocin-treated UCB-MSCs. Knock-down of MMP-2 by use of siRNA restored the tube formation, while reducing transmigration activity. In rats injected with oxytocin-treated UCB-MSCs, cardiac fibrosis and CD68 infiltration in the peri-infarct zone were reduced, whereas cell engraftment and connexin43 expression were greater than in rats injected with untreated UCB-MSCs. By contrast, angiogenesis did not differ significantly between the two groups. Cardiac contractility was higher in the group injected with oxytocin-treated UCB-MSCs than in the group injected with phosphate-buffered saline alone. Collectively, oxytocin is an effective priming reagent for stem cells for application to damaged heart tissue.
REFERENCES
- 1 Abbate A, Bussani R, Amin MS, Vetrovec GW, Baldi A. Acute myocardial infarction and heart failure: role of apoptosis. Int J Biochem Cell Biol 2006; 38: 1834–40.
- 2 Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701–5.
- 3 Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 2005; 115: 572–83.
- 4 Melo LG, Pachori AS, Kong D, et al. Molecular and cell-based therapies for protection, rescue, and repair of ischemic myocardium: reasons for cautious optimism. Circulation 2004; 109: 2386–93.
- 5 Caplice NM, Deb A. Myocardial-cell replacement: the science, the clinic and the future. Nat Clin Pract 2004; 1: 90–5.
- 6 Roobrouck VD, Ulloa-Montoya F, Verfaillie CM. Self-renewal and differentiation capacity of young and aged stem cells. Exp Cell Res 2008; 314: 1937–44.
- 7 Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells (Dayton, Ohio) 2003; 21: 105–10.
- 8 Mitchell JB, McIntosh K, Zvonic S, et al. Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells (Dayton, Ohio) 2006; 24: 376–85.
- 9 Parolini O, Alviano F, Bagnara GP, et al. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells (Dayton, Ohio) 2008; 26: 300–11.
- 10 Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem cells (Dayton, Ohio) 2006; 24: 1294–301.
- 11 Kajstura J, Rota M, Whang B, et al. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 2005; 96: 127–37.
- 12 Kinnaird T, Stabile E, Burnett MS, et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109: 1543–9.
- 13 Gnecchi M, He H, Liang OD, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 2005; 11: 367–8.
- 14 Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98: 1076–84.
- 15 Schachinger V, Erbs S, Elsasser A, et al. Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J 2006; 27: 2775–83.
- 16 Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 2006; 113: 1287–94.
- 17 Assmus B, Honold J, Schachinger V, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006; 355: 1222–32.
- 18 Zhang D, Fan GC, Zhou X, et al. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol 2008; 44: 281–92.
- 19 Kucic T, Copland IB, Cuerquis J, et al. Mesenchymal stromal cells genetically engineered to overexpress IGF-I enhance cell-based gene therapy of renal failure-induced anemia. Am J Physiol 2008 295; F488–96.
- 20 Okada H, Suzuki J, Futamatsu H, Maejima Y, Hirao K, Isobe M. Attenuation of autoimmune myocarditis in rats by mesenchymal stem cell transplantation through enhanced expression of hepatocyte growth factor. Int Heart J 2007; 48: 649–61.
- 21 Lim SY, Kim YS, Ahn Y, et al. The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. Cardiovascular Res. 2006; 70: 530–42.
- 22 Pasha Z, Wang Y, Sheikh R, Zhang D, Zhao T, Ashraf M. Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium. Cardiovasc Res 2008; 77: 134–42.
- 23 Erwin GS, Crisostomo PR, Wang Y, et al. Estradiol-treated mesenchymal stem cells improve myocardial recovery after ischemia. J Surg Res 2009; 152: 319–24.
- 24 Reversi A, Cassoni P, Chini B. Oxytocin receptor signaling in myoepithelial and cancer cells. J Mammary Gland Biol Neoplasia 2005; 10: 221–9.
- 25 Yazawa H, Hirasawa A, Horie K, et al. Oxytocin receptors expressed and coupled to Ca2+ signalling in a human vascular smooth muscle cell line. Br J Pharmacol 1996; 117: 799–804.
- 26 Thibonnier M, Conarty DM, Preston JA, Plesnicher CL, Dweik RA, Erzurum SC. Human vascular endothelial cells express oxytocin receptors. Endocrinology 1999; 140: 1301–9.
- 27 Tribollet E, Barberis C, Dreifuss JJ, Jard S. Autoradiographic localization of vasopressin and oxytocin binding sites in rat kidney. Kidney Int. 1988; 33: 959–65.
- 28 Ohmichi M, Koike K, Nohara A, et al. Oxytocin stimulates mitogen-activated protein kinase activity in cultured human puerperal uterine myometrial cells. Endocrinology 1995; 136: 2082–7.
- 29 Matsuura K, Nagai T, Nishigaki N, et al. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 2004; 279: 11384–91.
- 30 Danalache BA, Paquin J, Donghao W, et al. Nitric oxide signaling in oxytocin-mediated cardiomyogenesis. Stem Cells (Dayton, Ohio) 2007; 25: 679–88.
- 31 Cattaneo MG, Chini B, Vicentini LM. Oxytocin stimulates migration and invasion in human endothelial cells. Br J Pharmacol 2008; 153: 728–36.
- 32 Ponte AL, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells (Dayton, Ohio) 2007; 25: 1737–45.
- 33 Nagata J, Kijima H, Hatanaka H, et al. Angiopoietin-1 and vascular endothelial growth factor expression in human esophageal cancer. Int J Mol Med 2002; 10: 423–6.
- 34 De Becker A, Van Hummelen P, Bakkus M, Vande Broek I, et al. Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica 2007; 92: 440–9.
- 35 Cho PS, Messina DJ, Hirsh EL, et al. Immunogenicity of umbilical cord tissue derived cells. Blood 2008; 111: 430–8.
- 36 Steingen C, Brenig F, Baumgartner L, Schmidt J, Schmidt A, Bloch W. Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells. J Mol Cell Cardiol 2008; 44: 1072–84.
- 37 Schwartz MA, Horwitz AR. Integrating adhesion, protrusion, and contraction during cell migration. Cell 2006; 125: 1223–5.
- 38 Imanishi Y, Saito A, Komoda H, et al. Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute myocardial infarction in rats. J Mol Cell Cardiol 2008; 44: 662–71.
- 39 Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 2008; 103: 1204–19.
Citing Literature
