• 1.　沈陽(yáng)軍區(qū)總醫(yī)院 心血管外科，　沈陽(yáng)　110016;;
  • 2.　寧夏人民醫(yī)院　心血管外科，　銀川　750001;

目的　體外培養(yǎng)糖尿病與非糖尿病冠心病患者的骨髓間充質(zhì)干細(xì)胞（mesenchymal stem cells, MSCs），采用Affymetrix基因芯片技術(shù)對(duì)糖尿病與非糖尿病冠心病患者的MSCs功能基因表達(dá)譜進(jìn)行比較?！》椒ā」谛牟『喜⑻悄虿〗M納入1例患者，男，53歲；診斷：冠心病、2型糖尿病。非糖尿病冠心病組納入1例患者，男，51歲；診斷：冠心病。將兩組患者的骨髓淋巴細(xì)胞分離液采用密度梯度離心法和貼壁法進(jìn)行分離、提純MSCs，再用Affymetrix全基因組芯片檢測(cè)MSCs特異性功能蛋白基因表達(dá)的差異。　結(jié)果　冠心病合并糖尿病組功能蛋白表達(dá)基因中涉及細(xì)胞凋亡、細(xì)胞因子、細(xì)胞內(nèi)信號(hào)傳導(dǎo)系統(tǒng)的基因有27個(gè)，其中13個(gè)基因表達(dá)明顯上調(diào)，分別為
TNFRSF10B、TNFRSF21、NGF、CAV2、ITGA8、TNS1、ITGA2、AKT3、MBP、MAP2、INHBA、FST、PLA2G5；有14個(gè)基因表達(dá)明顯下調(diào)，分別為EPR1、BIRC5、HELLS、BCL2、HGF、CASP1、SEPP1、ITGA9、MAP2K6、RUNX3、TGFBR2、RUNX2、CTNNB1、CDC42?！〗Y(jié)論　糖尿病合并冠心病患者的MSCs在功能基因表達(dá)方面存在顯著變化。

引用本文： 劉宇,王輝山,黃建華,薛曉東,張哲俊. 糖尿病與非糖尿病冠心病患者骨髓間充質(zhì)干細(xì)胞基因表達(dá)差異的初步研究. 中國(guó)胸心血管外科臨床雜志, 2012, 19(4): 366-370. doi: 復(fù)制

1. 　Boilson B A, Gulati R. Stem cell therapy for the heart： a perspective. Transl Res, 2010, 155 （1）：3-5.
2. 　Kanaya AM, Grady D, Barrett-Connor E. Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus： a meta-analysis. Arch Intern Med, 2002, 162 （15）：1737-1745.
3. 　Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabet mellitus： insights fromm medchanistic studies. Lancet, 2008, 371（9626）： 1800-1809.
4. 　Kestendjieva S, Kyurkchiev D, Tsvetkova G, et al. Characterization of mesenchymal stem cells isolated from the human umbilical cord. Cell Biol Int, 2008, 32 （7）： 724-732.
5. 　Kumar S, Chanda D, Ponnazhagan S. Therapeutic potential of genetically modified mesenchymal stem cells. Gene Ther, 2008, 15 （10）：711-715.
6. 　Atoui R, Asenjo JF, Duong M, et al. Marrow stromal cells as universal donor cells for myocardial regenerative therapy： their unique immune tolerance. Ann Thorac Surg, 2008, 85 （2）：571-579.
7. 　Krause U, Harter C, Seckinger A, et al. Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infracted porcine heart. Stem Cells Dev, 2007, 16 （1）：31-37.
8. 　Atoui R, Shum-Tim D, Chiu R C. Myocardial regenerative therapy： immunologic bases for the potential “universal donor cells”. Ann Thorac Surg, 2008, 86 （1）：327-334.
9. 　Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem, 2006, 98 （5）：1076-1084.
10. 　Wang M, Crisostomo P R, Herring C, et al. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol, 2006, 291 （4）：R880-R884.
11. 　Kupatt C, Hostkotte J, Vlastos GA, et al. Embroyonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia. FASEB J, 2005, 19 （11）：1576-1578.
12. 　Gnecchi M, Zhang Z, Ni A, et al. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res, 2008, 103 （11）：1204-1219.
13. 　Capla JM, Grogan RH, Callaghan MJ, et al. Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia. Plast Reconstr Surg, 2007, 119 （1）：59-70.
14. 　Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation, 2002, 106 （22）：2781-2786.
15. 　Klima M, Zajedova J, Doubravska L, et al. Functional analysis of the posttranslational modifications of the death receptor 6. Biochim　Biophys Acta, 2009, 1793 （10）：1579-1587.
16. 　Mukherjee S, Lekli I, Das M, et al. Cardioprotection with alpha-tocopheryl phosphate： amelioration of myocardial ischemia reperfusion injury is linked with its ability to generate a survival signal through Akt activation. Biochim Biophys Acta, 2008, 1782 （9）：498-503.
17. 　Martindale JJ, Wall JA, Martinez-Longoria DM, et al. Overexpression of mitogen-activated protein kinase kinase 6 in the heart improves of functional recovery from ischemia in vitro and protects against myocardial infarction in vivo. J Biol Chem, 2005, 280 （1）：669-676.
18. 　Iwata A, Morgan-Stevenson V, Schwartz B, et al. Extracellular BCL2 proteins are danger-associated molecular patterns that reduce tissue damage in murine models of ischemia-reperfusion injury. PLoS One, 2010, 5 （2）：e9103.
19. 　Li W, Ma N, Ong LL, et al. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells, 2007, 25 （8）：2118-2127.
20. 　Siltanen A, Kitabayashi K, lakkisto P, et al. hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure. PLoS One, 2011, 6 （4）：e19161.
21. 　Ellison G M, Torella D, Dellegrottaglie S, et al. Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the inrarcted pig heart. J Am Coll Cardiol, 2011, 58 （9）：977-986.
22. 　Poppe A, Golsong P, Blumenthal B, et al. Hepatocyte growth factor-transfected skeletal myoblasts to limit the development of postinfarction heart failure. Artif Organs, 2012, 36 （3）：238-246.
  1. 1. 　Boilson B A, Gulati R. Stem cell therapy for the heart： a perspective. Transl Res, 2010, 155 （1）：3-5.
  2. 2. 　Kanaya AM, Grady D, Barrett-Connor E. Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus： a meta-analysis. Arch Intern Med, 2002, 162 （15）：1737-1745.
  3. 3. 　Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabet mellitus： insights fromm medchanistic studies. Lancet, 2008, 371（9626）： 1800-1809.
  4. 4. 　Kestendjieva S, Kyurkchiev D, Tsvetkova G, et al. Characterization of mesenchymal stem cells isolated from the human umbilical cord. Cell Biol Int, 2008, 32 （7）： 724-732.
  5. 5. 　Kumar S, Chanda D, Ponnazhagan S. Therapeutic potential of genetically modified mesenchymal stem cells. Gene Ther, 2008, 15 （10）：711-715.
  6. 6. 　Atoui R, Asenjo JF, Duong M, et al. Marrow stromal cells as universal donor cells for myocardial regenerative therapy： their unique immune tolerance. Ann Thorac Surg, 2008, 85 （2）：571-579.
  7. 7. 　Krause U, Harter C, Seckinger A, et al. Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infracted porcine heart. Stem Cells Dev, 2007, 16 （1）：31-37.
  8. 8. 　Atoui R, Shum-Tim D, Chiu R C. Myocardial regenerative therapy： immunologic bases for the potential “universal donor cells”. Ann Thorac Surg, 2008, 86 （1）：327-334.
  9. 9. 　Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem, 2006, 98 （5）：1076-1084.
  10. 10. 　Wang M, Crisostomo P R, Herring C, et al. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol, 2006, 291 （4）：R880-R884.
  11. 11. 　Kupatt C, Hostkotte J, Vlastos GA, et al. Embroyonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia. FASEB J, 2005, 19 （11）：1576-1578.
  12. 12. 　Gnecchi M, Zhang Z, Ni A, et al. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res, 2008, 103 （11）：1204-1219.
  13. 13. 　Capla JM, Grogan RH, Callaghan MJ, et al. Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia. Plast Reconstr Surg, 2007, 119 （1）：59-70.
  14. 14. 　Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation, 2002, 106 （22）：2781-2786.
  15. 15. 　Klima M, Zajedova J, Doubravska L, et al. Functional analysis of the posttranslational modifications of the death receptor 6. Biochim　Biophys Acta, 2009, 1793 （10）：1579-1587.
  16. 16. 　Mukherjee S, Lekli I, Das M, et al. Cardioprotection with alpha-tocopheryl phosphate： amelioration of myocardial ischemia reperfusion injury is linked with its ability to generate a survival signal through Akt activation. Biochim Biophys Acta, 2008, 1782 （9）：498-503.
  17. 17. 　Martindale JJ, Wall JA, Martinez-Longoria DM, et al. Overexpression of mitogen-activated protein kinase kinase 6 in the heart improves of functional recovery from ischemia in vitro and protects against myocardial infarction in vivo. J Biol Chem, 2005, 280 （1）：669-676.
  18. 18. 　Iwata A, Morgan-Stevenson V, Schwartz B, et al. Extracellular BCL2 proteins are danger-associated molecular patterns that reduce tissue damage in murine models of ischemia-reperfusion injury. PLoS One, 2010, 5 （2）：e9103.
  19. 19. 　Li W, Ma N, Ong LL, et al. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells, 2007, 25 （8）：2118-2127.
  20. 20. 　Siltanen A, Kitabayashi K, lakkisto P, et al. hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure. PLoS One, 2011, 6 （4）：e19161.
  21. 21. 　Ellison G M, Torella D, Dellegrottaglie S, et al. Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the inrarcted pig heart. J Am Coll Cardiol, 2011, 58 （9）：977-986.
  22. 22. 　Poppe A, Golsong P, Blumenthal B, et al. Hepatocyte growth factor-transfected skeletal myoblasts to limit the development of postinfarction heart failure. Artif Organs, 2012, 36 （3）：238-246.