Does diabetes mellitus influence angiogenesis-promoting effects of bone marrow-derived endothelial progenitor cell transplantation?

doi:10.3969/j.issn.2095-4344.2013.06.016

Abstract

Abstract:

BACKGROUND: As an angiogenic precursor cells, endothelial progenitor cells have a good prospect in the treatment of diabetic vascular disease by promotion of angiogenesis.
OBJECTIVE: To investigate the effects of diabetes mellitus on the promotion of angiogenesis in the ischemic lower limb by transplantation of bone marrow-derived endothelial progenitor cells.
METHODS: Rat models of diabetes mellitus were developed. Bone marrow mononuclear cells from the diabetes mellitus and normal rats were extracted and in vitro cultured towards endothelial progenitor cells. At the same time, diabetes mellitus and normal rat models of ischemic lower limb were established and received local transplantation of diabetes mellitus or normal rat endothelial progenitor cells or PBS into the ischemic region. After transplantation, vascular endothelial growth factor content and microvessel density in the lesion region were determined by ELISA and immunohistochemistry, respectively.
RESULTS AND CONCLUSION: (1) When the recipients were the same, there were no significant differences in vascular endothelial growth factor content and microvessel density in the ischemic tissue between different donors after transplantation of endothelial progenitor cells from diabetes mellitus or normal rats (P > 0.05). (2) When the donors were the same, vascular endothelial growth factor content and microvessel density in the ischemic tissue were significantly greater in the normal rats than those in the diabetes mellitus rats. These findings suggest that diabetes mellitus exhibits no effects on the promotion of angiogenesis by local transplantation of the in vitro cultured endothelial progenitor cells but it greatly impacts the microenvironment of the lesion regions where angiogenesis occurs.

Key words: stem cells, stem cell transplantation, endothelial progenitor cells, transplantation, diabetes mellitus, lower limb ischemia, angiogenesis, vascular endothelial growth factor, microvascular density

CLC Number:

R394.2

Zhou Chen-guang, Gong Jing-xin, Ma Yue, Zhou Ya-ru, Luan Feng, Yang Yan, Meng Jian-bo. Does diabetes mellitus influence angiogenesis-promoting effects of bone marrow-derived endothelial progenitor cell transplantation?[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(6): 1044-1048.

Figures/Tables 2

References

[1] Werner N, Kosiol S,Schiegl T,et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353(10):999-1007.

[2] Schmidtl C, Rossig L, Fichtlscherer S, et al. Reduced number of circulating endothelial progenitor ceils predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005; 111(22):2981-2987.

[3] Ai J, Wang N, Du J, et al. Zhongguo Yaolixue Tongbao. 2004; 20(11):1309-1312. 艾静,王宁,杜杰,等. Wistar大鼠2型糖尿病动物模型的建立[J].中国药理学通报,2004,20(11):1309-1312.

[4] Akarte AS, Srinivasan BP, Gandhi S. Vildagliptin selectively ameliorates GLP-1, GLUT4, SREBP-1c mRNA levels and stimulates β-Cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes. J Diabetes Complications. 2012 May 22.

[5] Bogoslovsky T, Chaudhry A, Latour L, et al. Endothelial progenitor cells correlate with lesion volume and growth in acute stroke. Neurology. 2010;75(23):2059-2062.

[6] Muthuraman A, Ramesh M, Sood S. Development of animal model for vasculatic neuropathy: Induction by ischemic-reperfusion in the rat femoral artery. J Neurosci Methods. 2010;186(2):215-221.

[7] Li Calzi S, Neu MB, Shaw LC,et al. Endothelial progenitor dysfunction in the pathogenesis of diabetic retinopathy: treatment concept to correct diabetes-associated deficits. EPMA J. 2010;1(1):88-100.

[8] Isner JM, Asahara T. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. Clin Invest. 1999;103(9):1231-1236.

[9] Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res. 2000; 55:15-36.

[10] Brea D, Rodríguez-González R,Sobrino T,et al. Proteomic analysis shows differential protein expression in endothelial progenitor cells between healthy subjects and ischemic stroke patients. Neurol Res. 2011;33(10):1057-1063.

[11] Grisar JC, Haddad F, Gomari FA, et al. Endothelial progenitor cells in cardiovascular disease and chronic inflammation: from biomarker to therapeutic agent. Biomark Med. 2011; 5(6):731-744.

[12] Lee MO, Song SH, Jung S, et al. Effect of ionizing radiation induced damage of endothelial progenitor cells in vascular regeneration.Arterioscler Thromb Vasc Biol. 2012;32(2): 343-352.

[13] Zeng L, Ding S, Yan Z, et al. Irradiation induces homing of donor endothelial progenitor cells in allogeneic hematopoietic stem cell transplantation. Hematol. 2012;95(2):189-197.

[14] Biscetti F, Straface G, De Cristofaro R, et al. High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism. Diabetes. 2010;59(6):1496-1505.

[15] Gehling UM, Ergün S, Schumacher U, et al. In vitro differentiation of endothelial cells form AC133-positive progenitor cells. Blood. 2000;95(10):3106-3112.

[16] Capobianco S, Chennamaneni V, Mittal M, et al. Endothelial progenitor cells as factors in neovascularization and endothelial repair. World J Cardiol. 2010;2(12):411-420.

[17] Suzukj T, NishdaM, Frtami S, et al. Neoendothelializalion after peripheral blood stem cell transplantation in humans: a case report of a Tokaimura nuclear accident victim. Cardiovasc Res. 2003;58(2):487-492.

[18] Jialal I, Fadini GP, Pollock K, et al.Circulating levels of endothelial progenitor cell mobilizing factors in the metabolic syndrome. Cardiol. 2010;106(11):1606-1608.

[19] Napoli C, Hayashi T, Cacciatore F, et al. Endothelial progenitor cells as therapeutic agents in the microcirculation: an update. Atherosclerosis. 2011;215(1):9-22.

[20] Jie KE, van der Putten K, Bergevoet MW, et al. Short- and long-term effects of erythropoietin treatment on endothelial progenitor cell levels in patients with cardiorenal syndrome. Heart. 2011;97(1):60-65.

[21] Smadja DM, Duong-van-Huyen JP, Dal Cortivo L, et al. Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia. Cytotherapy. 2012;14(2):232-239.

[22] Huang C, Zhang L, Wang Z, Pan H, et al. Endothelial progenitor cells are associated with plasma homocysteine in coronary artery disease.Acta Cardiol. 2011;66(6):773-777.

[23] McClung JA, Nasser N, Saleem M, et al. Circulating endothelial cells are elevated in patients with type 2 diabetes mellitus independently of HbA1c. Diabetologia. 2005;48(2): 345-350.

[24] Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53(1):195-199.

[25] Kuki S, Imanishi T, Kobayashi K. Hyperglycemia accelerated endothelial progenitor cell senescence via the activation of p38 mitogen activated protein kinase. Circ J, 2006;70(8): 1076-1081.

[26] Cubbon RM, Kahn MB, Wheatcroft SB. Effects of insulin resistance on endothelial progenitor cells and vascular repair. Clin Sci (Lond). 2009;117(5):173-190.