Skip to main content
Erschienen in: Current Diabetes Reports 4/2011

01.08.2011

Cell-Based Therapies for Diabetic Retinopathy

verfasst von: Lynn C. Shaw, Matthew B. Neu, Maria B. Grant

Erschienen in: Current Diabetes Reports | Ausgabe 4/2011

Einloggen, um Zugang zu erhalten

Abstract

Autologous endothelial progenitor cell (EPC) populations represent a novel treatment for therapeutic revascularization and vascular repair for diabetic patients with complications including diabetic retinopathy. Current therapies are applicable to late-stage disease and carry significant side effects, whereas cell-based therapy may provide an alternative by repairing areas of vasodegeneration and reversing ischemia. However, EPCs from diabetic patients with vascular complications are dysfunctional. Moreover, the diabetic environment poses its own challenges and complicates the use of autologous EPCs. Before EPCs become the ideal “cell therapy,” the optimal EPC must be determined, any functional dysfunction must be corrected prior to use, and the diabetic milieu will require modification to accept the EPCs. This review describes the rationale for harnessing the vascular reparative properties of EPCs with emphasis on the molecular and phenotypic nature of healthy EPCs, how diabetes alters them, and novel strategies to improve dysfunctional EPCs.
Literatur
1.
Zurück zum Zitat Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA. Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest. 2000;106:571–8.PubMedCrossRef Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA. Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest. 2000;106:571–8.PubMedCrossRef
2.
Zurück zum Zitat Loomans CJ, de Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53:195–9.PubMedCrossRef Loomans CJ, de Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53:195–9.PubMedCrossRef
3.
Zurück zum Zitat Caballero S, Sengupta N, Afzal A, Chang KH, Li Calzi S, et al. Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes. 2007;56:960–7.PubMedCrossRef Caballero S, Sengupta N, Afzal A, Chang KH, Li Calzi S, et al. Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes. 2007;56:960–7.PubMedCrossRef
4.
Zurück zum Zitat Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002;106:2781–6.PubMedCrossRef Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002;106:2781–6.PubMedCrossRef
5.
Zurück zum Zitat Fadini GP, Agostini C, Avogaro A. Endothelial progenitor cells and vascular biology in diabetes mellitus: current knowledge and future perspectives. Curr Diab Rev. 2005;1:41–58.CrossRef Fadini GP, Agostini C, Avogaro A. Endothelial progenitor cells and vascular biology in diabetes mellitus: current knowledge and future perspectives. Curr Diab Rev. 2005;1:41–58.CrossRef
6.
Zurück zum Zitat Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005;45:1449–57.PubMedCrossRef Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005;45:1449–57.PubMedCrossRef
7.
Zurück zum Zitat Zacchigna S, Ruiz de Almodovar C, Carmeliet P. Similarities between angiogenesis and neural development: what small animal models can tell us. Curr Top Dev Biol. 2008;80:1–55.PubMedCrossRef Zacchigna S, Ruiz de Almodovar C, Carmeliet P. Similarities between angiogenesis and neural development: what small animal models can tell us. Curr Top Dev Biol. 2008;80:1–55.PubMedCrossRef
8.
Zurück zum Zitat Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, et al. HMG-CoA reductase inhibitor mobilizes bone marrow–derived endothelial progenitor cells. J Clin Invest. 2001;108:399–405.PubMed Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, et al. HMG-CoA reductase inhibitor mobilizes bone marrow–derived endothelial progenitor cells. J Clin Invest. 2001;108:399–405.PubMed
9.
Zurück zum Zitat Sengupta N, Caballero S, Mames RN, Timmers AM, Saban D, et al. Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors. Invest Ophthalmol Vis Sci. 2005;46:343–8.PubMedCrossRef Sengupta N, Caballero S, Mames RN, Timmers AM, Saban D, et al. Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors. Invest Ophthalmol Vis Sci. 2005;46:343–8.PubMedCrossRef
10.
Zurück zum Zitat Tepper OM, Capla JM, Galiano RD, Ceradini DJ, Callaghan MJ, et al. Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells. Blood. 2005;105:1068–77.PubMedCrossRef Tepper OM, Capla JM, Galiano RD, Ceradini DJ, Callaghan MJ, et al. Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells. Blood. 2005;105:1068–77.PubMedCrossRef
11.
Zurück zum Zitat Lin Y, Weisdorf DJ, Solovey A, Hebbel RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000;105:71–7.PubMedCrossRef Lin Y, Weisdorf DJ, Solovey A, Hebbel RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000;105:71–7.PubMedCrossRef
12.
Zurück zum Zitat Zengin E, Chalajour F, Gehling UM, Ito WD, Treede H, et al. Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development. 2006;133:1543–51.PubMedCrossRef Zengin E, Chalajour F, Gehling UM, Ito WD, Treede H, et al. Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development. 2006;133:1543–51.PubMedCrossRef
13.
Zurück zum Zitat Yoder MC. Is endothelium the origin of endothelial progenitor cells? Arterioscler Thromb Vasc Biol. 30:1094–103 Yoder MC. Is endothelium the origin of endothelial progenitor cells? Arterioscler Thromb Vasc Biol. 30:1094–103
14.
Zurück zum Zitat Ingram DA, Mead LE, Moore DB, Woodard W, Fenoglio A, et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood. 2005;105:2783–6.PubMedCrossRef Ingram DA, Mead LE, Moore DB, Woodard W, Fenoglio A, et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood. 2005;105:2783–6.PubMedCrossRef
15.
Zurück zum Zitat Timmermans F, Velghe I, Vanwalleghem L, De Smedt M, Van Coppernolle S, et al. Generation of T cells from human embryonic stem cell-derived hematopoietic zones. J Immunol. 2009;182:6879–88.PubMedCrossRef Timmermans F, Velghe I, Vanwalleghem L, De Smedt M, Van Coppernolle S, et al. Generation of T cells from human embryonic stem cell-derived hematopoietic zones. J Immunol. 2009;182:6879–88.PubMedCrossRef
16.
Zurück zum Zitat Watt SM, Athanassopoulos A, Harris AL, Tsaknakis G. Human endothelial stem/progenitor cells, angiogenic factors and vascular repair. J R Soc Interface. 7 Suppl 6:S731-51 Watt SM, Athanassopoulos A, Harris AL, Tsaknakis G. Human endothelial stem/progenitor cells, angiogenic factors and vascular repair. J R Soc Interface. 7 Suppl 6:S731-51
17.
Zurück zum Zitat Madeddu P. Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp Physiol. 2005;90:315–26.PubMedCrossRef Madeddu P. Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp Physiol. 2005;90:315–26.PubMedCrossRef
18.
Zurück zum Zitat Gulati R, Simari RD. Cell therapy for acute myocardial infarction. Med Clin North Am. 2007;91:769–85. xiii.PubMedCrossRef Gulati R, Simari RD. Cell therapy for acute myocardial infarction. Med Clin North Am. 2007;91:769–85. xiii.PubMedCrossRef
19.
Zurück zum Zitat Sieveking DP, Ng MK. Cell therapies for therapeutic angiogenesis: back to the bench. Vasc Med. 2009;14:153–66.PubMedCrossRef Sieveking DP, Ng MK. Cell therapies for therapeutic angiogenesis: back to the bench. Vasc Med. 2009;14:153–66.PubMedCrossRef
20.
Zurück zum Zitat •• Busik JV, Tikhonenko M, Bhatwadekar A, Opreanu M, Yakubova N, et al. Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock. J Exp Med. 2009;206:2897–906. This manuscript characterizes a specific EPC defect in diabetes, the loss of circadian rhythmicity of EPC release from the bone marrow. The manuscript describes studies in a rat model of type 2 diabetes that demonstrates bone marrow neuropathy proceeds the development of diabetic retinopathy and that the loss of bone marrow innervation is responsible for the abnormal EPC release.PubMedCrossRef •• Busik JV, Tikhonenko M, Bhatwadekar A, Opreanu M, Yakubova N, et al. Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock. J Exp Med. 2009;206:2897–906. This manuscript characterizes a specific EPC defect in diabetes, the loss of circadian rhythmicity of EPC release from the bone marrow. The manuscript describes studies in a rat model of type 2 diabetes that demonstrates bone marrow neuropathy proceeds the development of diabetic retinopathy and that the loss of bone marrow innervation is responsible for the abnormal EPC release.PubMedCrossRef
21.
Zurück zum Zitat Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003;102:1340–6.PubMedCrossRef Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003;102:1340–6.PubMedCrossRef
22.
Zurück zum Zitat Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18:3964–72.PubMedCrossRef Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18:3964–72.PubMedCrossRef
23.
Zurück zum Zitat Wolfram O, Jentsch-Ullrich K, Wagner A, Hammwohner M, Steinke R, et al. G-CSF-induced mobilization of CD34(+) progenitor cells and proarrhythmic effects in patients with severe coronary artery disease. Pacing Clin Electrophysiol. 2007;30 Suppl 1:S166–169.PubMed Wolfram O, Jentsch-Ullrich K, Wagner A, Hammwohner M, Steinke R, et al. G-CSF-induced mobilization of CD34(+) progenitor cells and proarrhythmic effects in patients with severe coronary artery disease. Pacing Clin Electrophysiol. 2007;30 Suppl 1:S166–169.PubMed
24.
Zurück zum Zitat Bhatwadekar AD, Glenn JV, Curtis TM, Grant MB, Stitt AW, et al. Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells. Invest Ophthalmol Vis Sci. 2009;50:4967–73.PubMedCrossRef Bhatwadekar AD, Glenn JV, Curtis TM, Grant MB, Stitt AW, et al. Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells. Invest Ophthalmol Vis Sci. 2009;50:4967–73.PubMedCrossRef
25.
Zurück zum Zitat Ceradini DJ, Gurtner GC. Homing to hypoxia: HIF-1 as a mediator of progenitor cell recruitment to injured tissue. Trends Cardiovasc Med. 2005;15:57–63.PubMedCrossRef Ceradini DJ, Gurtner GC. Homing to hypoxia: HIF-1 as a mediator of progenitor cell recruitment to injured tissue. Trends Cardiovasc Med. 2005;15:57–63.PubMedCrossRef
26.
Zurück zum Zitat Butler JM, Guthrie SM, Koc M, Afzal A, Caballero S, et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest. 2005;115:86–93.PubMed Butler JM, Guthrie SM, Koc M, Afzal A, Caballero S, et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest. 2005;115:86–93.PubMed
27.
Zurück zum Zitat Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.PubMedCrossRef Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.PubMedCrossRef
28.
Zurück zum Zitat Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600.PubMedCrossRef Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600.PubMedCrossRef
29.
Zurück zum Zitat Urbich C, Dimmeler S. Endothelial progenitor cells functional characterization. Trends Cardiovasc Med. 2004;14:318–22.PubMedCrossRef Urbich C, Dimmeler S. Endothelial progenitor cells functional characterization. Trends Cardiovasc Med. 2004;14:318–22.PubMedCrossRef
30.
Zurück zum Zitat Sieveking DP, Buckle A, Celermajer DS, Ng MK. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations: insights from a novel human angiogenesis assay. J Am Coll Cardiol. 2008;51:660–8.PubMedCrossRef Sieveking DP, Buckle A, Celermajer DS, Ng MK. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations: insights from a novel human angiogenesis assay. J Am Coll Cardiol. 2008;51:660–8.PubMedCrossRef
31.
Zurück zum Zitat Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, et al. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol. 2005;39:733–42.PubMedCrossRef Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, et al. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol. 2005;39:733–42.PubMedCrossRef
32.
Zurück zum Zitat Mukai S, Fukushima T, Naka D, Tanaka H, Osada Y, et al. Activation of hepatocyte growth factor activator zymogen (pro-HGFA) by human kallikrein 1-related peptidases. FEBS J. 2008;275:1003–17.PubMedCrossRef Mukai S, Fukushima T, Naka D, Tanaka H, Osada Y, et al. Activation of hepatocyte growth factor activator zymogen (pro-HGFA) by human kallikrein 1-related peptidases. FEBS J. 2008;275:1003–17.PubMedCrossRef
33.
Zurück zum Zitat Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164–9.PubMedCrossRef Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164–9.PubMedCrossRef
34.
Zurück zum Zitat Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109:1801–9.PubMedCrossRef Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109:1801–9.PubMedCrossRef
35.
Zurück zum Zitat Reinisch A, Hofmann NA, Obenauf AC, Kashofer K, Rohde E, et al. Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo. Blood. 2009;113:6716–25.PubMedCrossRef Reinisch A, Hofmann NA, Obenauf AC, Kashofer K, Rohde E, et al. Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo. Blood. 2009;113:6716–25.PubMedCrossRef
36.
Zurück zum Zitat He T, Lu T, d’Uscio LV, Lam CF, Lee HC, et al. Angiogenic function of prostacyclin biosynthesis in human endothelial progenitor cells. Circ Res. 2008;103:80–8.PubMedCrossRef He T, Lu T, d’Uscio LV, Lam CF, Lee HC, et al. Angiogenic function of prostacyclin biosynthesis in human endothelial progenitor cells. Circ Res. 2008;103:80–8.PubMedCrossRef
37.
Zurück zum Zitat •• Medina RJ, O’Neill CL, Humphreys MW, Gardiner TA, Stitt AW. Outgrowth endothelial cells: characterization and their potential for reversing ischemic retinopathy. Invest Ophthalmol Vis Sci. 2010;51:5906–13. The authors show OECs are committed to an endothelial lineage and have significant proliferative and de novo tubulogenic potential. OECs closely interacted with endothelial cells through adherens and tight junctions and integrated into retinal vascular networks in vitro. Using a murine model of retinal ischemia, the authors demonstrated that OECs directly incorporate into the resident vasculature, significantly decreasing avascular areas, concomitantly increasing normovascular areas, and preventing pathologic preretinal neovascularization. The authors conclude that OECs have potential as therapeutic cells to vascularize the ischemic retina.PubMedCrossRef •• Medina RJ, O’Neill CL, Humphreys MW, Gardiner TA, Stitt AW. Outgrowth endothelial cells: characterization and their potential for reversing ischemic retinopathy. Invest Ophthalmol Vis Sci. 2010;51:5906–13. The authors show OECs are committed to an endothelial lineage and have significant proliferative and de novo tubulogenic potential. OECs closely interacted with endothelial cells through adherens and tight junctions and integrated into retinal vascular networks in vitro. Using a murine model of retinal ischemia, the authors demonstrated that OECs directly incorporate into the resident vasculature, significantly decreasing avascular areas, concomitantly increasing normovascular areas, and preventing pathologic preretinal neovascularization. The authors conclude that OECs have potential as therapeutic cells to vascularize the ischemic retina.PubMedCrossRef
38.
Zurück zum Zitat Yoon CH, Hur J, Park KW, Kim JH, Lee CS, et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: the role of angiogenic cytokines and matrix metalloproteinases. Circulation. 2005;112:1618–27.PubMedCrossRef Yoon CH, Hur J, Park KW, Kim JH, Lee CS, et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: the role of angiogenic cytokines and matrix metalloproteinases. Circulation. 2005;112:1618–27.PubMedCrossRef
39.
Zurück zum Zitat Chan-Ling T, Baxter L, Afzal A, Sengupta N, Caballero S, et al. Hematopoietic stem cells provide repair functions after laser-induced Bruch’s membrane rupture model of choroidal neovascularization. Am J Pathol. 2006;168:1031–44.PubMedCrossRef Chan-Ling T, Baxter L, Afzal A, Sengupta N, Caballero S, et al. Hematopoietic stem cells provide repair functions after laser-induced Bruch’s membrane rupture model of choroidal neovascularization. Am J Pathol. 2006;168:1031–44.PubMedCrossRef
40.
41.
Zurück zum Zitat Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L, et al. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res. 2008;103:194–202.PubMedCrossRef Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L, et al. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res. 2008;103:194–202.PubMedCrossRef
42.
Zurück zum Zitat Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105:93–8.PubMedCrossRef Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105:93–8.PubMedCrossRef
43.
Zurück zum Zitat Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–76.PubMedCrossRef Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–76.PubMedCrossRef
44.
Zurück zum Zitat Caspi O, Huber I, Kehat I, Habib M, Arbel G, et al. Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol. 2007;50:1884–93.PubMedCrossRef Caspi O, Huber I, Kehat I, Habib M, Arbel G, et al. Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol. 2007;50:1884–93.PubMedCrossRef
45.
Zurück zum Zitat Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A. Cardiac cell repair therapy: a clinical perspective. Mayo Clin Proc. 2009;84:876–92.PubMedCrossRef Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A. Cardiac cell repair therapy: a clinical perspective. Mayo Clin Proc. 2009;84:876–92.PubMedCrossRef
46.
Zurück zum Zitat Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001;65:845–7.PubMedCrossRef Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001;65:845–7.PubMedCrossRef
47.
Zurück zum Zitat Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002;106:1913–8.PubMedCrossRef Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002;106:1913–8.PubMedCrossRef
48.
Zurück zum Zitat Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med. 2003;9:702–12.PubMedCrossRef Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med. 2003;9:702–12.PubMedCrossRef
49.
Zurück zum Zitat Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355:1199–209.PubMedCrossRef Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355:1199–209.PubMedCrossRef
50.
Zurück zum Zitat Tongers J, Roncalli JG, Losordo DW. Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation. Microvasc Res. 79:200–06. Tongers J, Roncalli JG, Losordo DW. Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation. Microvasc Res. 79:200–06.
51.
Zurück zum Zitat Beeres SL, Atsma DE, van Ramshorst J, Schalij MJ, Bax JJ. Cell therapy for ischaemic heart disease. Heart. 2008;94:1214–26.PubMedCrossRef Beeres SL, Atsma DE, van Ramshorst J, Schalij MJ, Bax JJ. Cell therapy for ischaemic heart disease. Heart. 2008;94:1214–26.PubMedCrossRef
52.
Zurück zum Zitat Awad O, Jiao C, Ma N, Dunnwald M, Schatteman GC. Obese diabetic mouse environment differentially affects primitive and monocytic endothelial cell progenitors. Stem Cells. 2005;23:575–83.PubMedCrossRef Awad O, Jiao C, Ma N, Dunnwald M, Schatteman GC. Obese diabetic mouse environment differentially affects primitive and monocytic endothelial cell progenitors. Stem Cells. 2005;23:575–83.PubMedCrossRef
53.
Zurück zum Zitat Loomans CJ, van Haperen R, Duijs JM, Verseyden C, de Crom R, et al. Differentiation of bone marrow-derived endothelial progenitor cells is shifted into a proinflammatory phenotype by hyperglycemia. Mol Med. 2009;15:152–9.PubMedCrossRef Loomans CJ, van Haperen R, Duijs JM, Verseyden C, de Crom R, et al. Differentiation of bone marrow-derived endothelial progenitor cells is shifted into a proinflammatory phenotype by hyperglycemia. Mol Med. 2009;15:152–9.PubMedCrossRef
54.
Zurück zum Zitat Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation. 2002;105:1656–62.PubMedCrossRef Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation. 2002;105:1656–62.PubMedCrossRef
55.
Zurück zum Zitat Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension. 2005;45:321–5.PubMedCrossRef Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension. 2005;45:321–5.PubMedCrossRef
56.
Zurück zum Zitat Urao N, Okigaki M, Yamada H, Aadachi Y, Matsuno K, et al. Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res. 2006;98:1405–13.PubMedCrossRef Urao N, Okigaki M, Yamada H, Aadachi Y, Matsuno K, et al. Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res. 2006;98:1405–13.PubMedCrossRef
57.
Zurück zum Zitat Segal MS, Shah R, Afzal A, Perrault CM, Chang K, et al. Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes. 2006;55:102–9.PubMedCrossRef Segal MS, Shah R, Afzal A, Perrault CM, Chang K, et al. Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes. 2006;55:102–9.PubMedCrossRef
58.
Zurück zum Zitat Jarajapu YP, Grant MB. The promise of cell-based therapies for diabetic complications: challenges and solutions. Circ Res. 106:854–69. Jarajapu YP, Grant MB. The promise of cell-based therapies for diabetic complications: challenges and solutions. Circ Res. 106:854–69.
59.
Zurück zum Zitat He T, Peterson TE, Holmuhamedov EL, Terzic A, Caplice NM, et al. Human endothelial progenitor cells tolerate oxidative stress due to intrinsically high expression of manganese superoxide dismutase. Arterioscler Thromb Vasc Biol. 2004;24:2021–7.PubMedCrossRef He T, Peterson TE, Holmuhamedov EL, Terzic A, Caplice NM, et al. Human endothelial progenitor cells tolerate oxidative stress due to intrinsically high expression of manganese superoxide dismutase. Arterioscler Thromb Vasc Biol. 2004;24:2021–7.PubMedCrossRef
60.
Zurück zum Zitat Togliatto G, Trombetta A, Dentelli P, Baragli A, Rosso A, et al. Unacylated ghrelin rescues endothelial progenitor cell function in individuals with type 2 diabetes. Diabetes. 59:1016–25. Togliatto G, Trombetta A, Dentelli P, Baragli A, Rosso A, et al. Unacylated ghrelin rescues endothelial progenitor cell function in individuals with type 2 diabetes. Diabetes. 59:1016–25.
61.
Zurück zum Zitat He T, Joyner MJ, Katusic ZS. Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells. Microvasc Res. 2009;78:447–52.PubMedCrossRef He T, Joyner MJ, Katusic ZS. Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells. Microvasc Res. 2009;78:447–52.PubMedCrossRef
62.
Zurück zum Zitat Ingram DA, Krier TR, Mead LE, McGuire C, Prater DN, et al. Clonogenic endothelial progenitor cells are sensitive to oxidative stress. Stem Cells. 2007;25:297–304.PubMedCrossRef Ingram DA, Krier TR, Mead LE, McGuire C, Prater DN, et al. Clonogenic endothelial progenitor cells are sensitive to oxidative stress. Stem Cells. 2007;25:297–304.PubMedCrossRef
63.
Zurück zum Zitat Urbich C, Dernbach E, Rossig L, Zeiher AM, Dimmeler S. High glucose reduces cathepsin L activity and impairs invasion of circulating progenitor cells. J Mol Cell Cardiol. 2008;45:429–36.PubMedCrossRef Urbich C, Dernbach E, Rossig L, Zeiher AM, Dimmeler S. High glucose reduces cathepsin L activity and impairs invasion of circulating progenitor cells. J Mol Cell Cardiol. 2008;45:429–36.PubMedCrossRef
64.
Zurück zum Zitat Ii M, Takenaka H, Asai J, Ibusuki K, Mizukami Y, et al. Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circ Res. 2006;98:697–704.PubMedCrossRef Ii M, Takenaka H, Asai J, Ibusuki K, Mizukami Y, et al. Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circ Res. 2006;98:697–704.PubMedCrossRef
65.
Zurück zum Zitat Tan K, Lessieur E, Cutler A, Nerone P, Vasanji A, et al. Impaired function of circulating CD34(+) CD45(−) cells in patients with proliferative diabetic retinopathy. Exp Eye Res. 91:229–37. Tan K, Lessieur E, Cutler A, Nerone P, Vasanji A, et al. Impaired function of circulating CD34(+) CD45(−) cells in patients with proliferative diabetic retinopathy. Exp Eye Res. 91:229–37.
66.
Zurück zum Zitat Cho HJ, Kim HS, Lee MM, Kim DH, Yang HJ, et al. Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation. Circulation. 2003;108:2918–25.PubMedCrossRef Cho HJ, Kim HS, Lee MM, Kim DH, Yang HJ, et al. Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation. Circulation. 2003;108:2918–25.PubMedCrossRef
67.
Zurück zum Zitat Hwang JH, Kim SW, Park SE, Yun HJ, Lee Y, et al. Overexpression of stromal cell-derived factor-1 enhances endothelium-supported transmigration, maintenance, and proliferation of hematopoietic progenitor cells. Stem Cells Dev. 2006;15:260–8.PubMedCrossRef Hwang JH, Kim SW, Park SE, Yun HJ, Lee Y, et al. Overexpression of stromal cell-derived factor-1 enhances endothelium-supported transmigration, maintenance, and proliferation of hematopoietic progenitor cells. Stem Cells Dev. 2006;15:260–8.PubMedCrossRef
68.
Zurück zum Zitat Sorrentino SA, Bahlmann FH, Besler C, Muller M, Schulz S, et al. Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation. 2007;116:163–73.PubMedCrossRef Sorrentino SA, Bahlmann FH, Besler C, Muller M, Schulz S, et al. Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation. 2007;116:163–73.PubMedCrossRef
69.
Zurück zum Zitat Mohler 3rd ER, Shi Y, Moore J, Bantly A, Hamamdzic D, et al. Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol. Cytom A. 2009;75:75–82.CrossRef Mohler 3rd ER, Shi Y, Moore J, Bantly A, Hamamdzic D, et al. Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol. Cytom A. 2009;75:75–82.CrossRef
70.
Zurück zum Zitat Ingram DA, Lien IZ, Mead LE, Estes M, Prater DN, et al. In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell numbers and function. Diabetes. 2008;57:724–31.PubMedCrossRef Ingram DA, Lien IZ, Mead LE, Estes M, Prater DN, et al. In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell numbers and function. Diabetes. 2008;57:724–31.PubMedCrossRef
71.
Zurück zum Zitat Bhatwadekar A, Glenn JV, Figarola JL, Scott S, Gardiner TA, et al. A new advanced glycation inhibitor, LR-90, prevents experimental diabetic retinopathy in rats. Br J Ophthalmol. 2008;92:545–7.PubMedCrossRef Bhatwadekar A, Glenn JV, Figarola JL, Scott S, Gardiner TA, et al. A new advanced glycation inhibitor, LR-90, prevents experimental diabetic retinopathy in rats. Br J Ophthalmol. 2008;92:545–7.PubMedCrossRef
72.
Zurück zum Zitat Dorrell MI, Otani A, Aguilar E, Moreno SK, Friedlander M. Adult bone marrow-derived stem cells use R-cadherin to target sites of neovascularization in the developing retina. Blood. 2004;103:3420–7.PubMedCrossRef Dorrell MI, Otani A, Aguilar E, Moreno SK, Friedlander M. Adult bone marrow-derived stem cells use R-cadherin to target sites of neovascularization in the developing retina. Blood. 2004;103:3420–7.PubMedCrossRef
73.
Zurück zum Zitat Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, et al. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med. 2002;8:1004–10.PubMedCrossRef Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, et al. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med. 2002;8:1004–10.PubMedCrossRef
74.
Zurück zum Zitat Otani A, Dorrell MI, Kinder K, Moreno SK, Nusinowitz S, et al. Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest. 2004;114:765–74.PubMed Otani A, Dorrell MI, Kinder K, Moreno SK, Nusinowitz S, et al. Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest. 2004;114:765–74.PubMed
75.
Zurück zum Zitat Ritter MR, Banin E, Moreno SK, Aguilar E, Dorrell MI, et al. Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy. J Clin Invest. 2006;116:3266–76.PubMedCrossRef Ritter MR, Banin E, Moreno SK, Aguilar E, Dorrell MI, et al. Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy. J Clin Invest. 2006;116:3266–76.PubMedCrossRef
76.
Zurück zum Zitat Kramerov AA, Saghizadeh M, Caballero S, Shaw LC, Li Calzi S, et al. Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites. Mol Cell Biochem. 2008;316:177–86.PubMedCrossRef Kramerov AA, Saghizadeh M, Caballero S, Shaw LC, Li Calzi S, et al. Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites. Mol Cell Biochem. 2008;316:177–86.PubMedCrossRef
77.
Zurück zum Zitat Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol. 22:231–7. Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol. 22:231–7.
78.
Zurück zum Zitat Caballero S, Yang R, Grant MB, Chaqour B. Selective blockade of cytoskeletal actin remodeling reduces experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. Caballero S, Yang R, Grant MB, Chaqour B. Selective blockade of cytoskeletal actin remodeling reduces experimental choroidal neovascularization. Invest Ophthalmol Vis Sci.
79.
Zurück zum Zitat Chakravarthy U, Gardiner TA. Endothelium-derived agents in pericyte function/dysfunction. Prog Retin Eye Res. 1999;18:511–27.PubMedCrossRef Chakravarthy U, Gardiner TA. Endothelium-derived agents in pericyte function/dysfunction. Prog Retin Eye Res. 1999;18:511–27.PubMedCrossRef
80.
Zurück zum Zitat Ding R, Darland DC, Parmacek MS, D’Amore PA. Endothelial-mesenchymal interactions in vitro reveal molecular mechanisms of smooth muscle/pericyte differentiation. Stem Cells Dev. 2004;13:509–20.PubMed Ding R, Darland DC, Parmacek MS, D’Amore PA. Endothelial-mesenchymal interactions in vitro reveal molecular mechanisms of smooth muscle/pericyte differentiation. Stem Cells Dev. 2004;13:509–20.PubMed
81.
Zurück zum Zitat Puro DG. Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. Microcirculation. 2007;14:1–10.PubMedCrossRef Puro DG. Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. Microcirculation. 2007;14:1–10.PubMedCrossRef
82.
Zurück zum Zitat Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97:512–23.PubMedCrossRef Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97:512–23.PubMedCrossRef
83.
Zurück zum Zitat Campagnolo P, Wong MM, Xu Q. Progenitor cells in arteriosclerosis: good or bad guys? Antioxid Redox Signal. Campagnolo P, Wong MM, Xu Q. Progenitor cells in arteriosclerosis: good or bad guys? Antioxid Redox Signal.
84.
Zurück zum Zitat Assmus B, Urbich C, Aicher A, Hofmann WK, Haendeler J, et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ Res. 2003;92:1049–55.PubMedCrossRef Assmus B, Urbich C, Aicher A, Hofmann WK, Haendeler J, et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ Res. 2003;92:1049–55.PubMedCrossRef
85.
Zurück zum Zitat Besler C, Doerries C, Giannotti G, Luscher TF, Landmesser U. Pharmacological approaches to improve endothelial repair mechanisms. Expert Rev Cardiovasc Ther. 2008;6:1071–82.PubMedCrossRef Besler C, Doerries C, Giannotti G, Luscher TF, Landmesser U. Pharmacological approaches to improve endothelial repair mechanisms. Expert Rev Cardiovasc Ther. 2008;6:1071–82.PubMedCrossRef
86.
Zurück zum Zitat Bahlmann FH, De Groot K, Spandau JM, Landry AL, Hertel B, et al. Erythropoietin regulates endothelial progenitor cells. Blood. 2004;103:921–6.PubMedCrossRef Bahlmann FH, De Groot K, Spandau JM, Landry AL, Hertel B, et al. Erythropoietin regulates endothelial progenitor cells. Blood. 2004;103:921–6.PubMedCrossRef
87.
Zurück zum Zitat •• Bhatwadekar AD, Guerin EP, Jarajapu YP, Caballero S, Sheridan C, et al. Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions. Diabetes. 2010;59:2010–9. The studies presented in this manuscript show that transient inhibition of TGF-β1 in CD34+ cells ex vivo enhances repair after vascular damage. This finding may have a profound impact on disease states associated with vascular dysfunction such as ischemic heart disease and diabetic vascular complications. Autologous cellular therapy has not been feasible in diabetic patients because of dysfunctional cells. The transient inhibition of TGF-β1 may represent a promising therapeutic strategy for restoring vascular reparative function in diabetic CD34+ cells and may increase the likelihood of successful cellular therapy in diabetic individuals.PubMedCrossRef •• Bhatwadekar AD, Guerin EP, Jarajapu YP, Caballero S, Sheridan C, et al. Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions. Diabetes. 2010;59:2010–9. The studies presented in this manuscript show that transient inhibition of TGF-β1 in CD34+ cells ex vivo enhances repair after vascular damage. This finding may have a profound impact on disease states associated with vascular dysfunction such as ischemic heart disease and diabetic vascular complications. Autologous cellular therapy has not been feasible in diabetic patients because of dysfunctional cells. The transient inhibition of TGF-β1 may represent a promising therapeutic strategy for restoring vascular reparative function in diabetic CD34+ cells and may increase the likelihood of successful cellular therapy in diabetic individuals.PubMedCrossRef
88.
Zurück zum Zitat Marrotte EJ, Chen DD, Hakim JS, Chen AF. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice. J Clin Invest. 120:4207–19. Marrotte EJ, Chen DD, Hakim JS, Chen AF. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice. J Clin Invest. 120:4207–19.
89.
Zurück zum Zitat Matsuura K, Hagiwara N. The pleiotropic effects of ARB in vascular endothelial progenitor cells. Curr Vasc Pharmacol. Matsuura K, Hagiwara N. The pleiotropic effects of ARB in vascular endothelial progenitor cells. Curr Vasc Pharmacol.
90.
Zurück zum Zitat Sampaio WO, Henrique de Castro C, Santos RA, Schiffrin EL, Touyz RM. Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension. 2007;50:1093–8.PubMedCrossRef Sampaio WO, Henrique de Castro C, Santos RA, Schiffrin EL, Touyz RM. Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension. 2007;50:1093–8.PubMedCrossRef
91.
Zurück zum Zitat Benter IF, Yousif MH, Dhaunsi GS, Kaur J, Chappell MC, et al. Angiotensin-(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats. Am J Nephrol. 2008;28:25–33.PubMedCrossRef Benter IF, Yousif MH, Dhaunsi GS, Kaur J, Chappell MC, et al. Angiotensin-(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats. Am J Nephrol. 2008;28:25–33.PubMedCrossRef
92.
Zurück zum Zitat Iusuf D, Henning RH, van Gilst WH, Roks AJ. Angiotensin-(1-7): pharmacological properties and pharmacotherapeutic perspectives. Eur J Pharmacol. 2008;585:303–12.PubMedCrossRef Iusuf D, Henning RH, van Gilst WH, Roks AJ. Angiotensin-(1-7): pharmacological properties and pharmacotherapeutic perspectives. Eur J Pharmacol. 2008;585:303–12.PubMedCrossRef
93.
Zurück zum Zitat Jarajapu YPR, Bhatwadekar AD, Caballero S, et al. Protection from diabetes-induced endothelial progenitor cell dysfunction by ACE2/Angiotensin-(1-7)/Mas receptor axis. Presented at the Experimental Biology Conference. Washington, D.C. April 9–13, 2011. Jarajapu YPR, Bhatwadekar AD, Caballero S, et al. Protection from diabetes-induced endothelial progenitor cell dysfunction by ACE2/Angiotensin-(1-7)/Mas receptor axis. Presented at the Experimental Biology Conference. Washington, D.C. April 9–13, 2011.
94.
Zurück zum Zitat Chang J, Li Y, Huang Y, Lam KS, Hoo RL, et al. Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway. Diabetes. 59:2949–59. Chang J, Li Y, Huang Y, Lam KS, Hoo RL, et al. Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A signaling pathway. Diabetes. 59:2949–59.
95.
Zurück zum Zitat Sapieha P, Joyal JS, Rivera JC, Kermorvant-Duchemin E, Sennlaub F, et al. Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life. J Clin Invest. 120:3022–32. Sapieha P, Joyal JS, Rivera JC, Kermorvant-Duchemin E, Sennlaub F, et al. Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life. J Clin Invest. 120:3022–32.
96.
Zurück zum Zitat Parodi MB, Bandello F. Branch retinal vein occlusion: classification and treatment. Ophthalmologica. 2009;223:298–305.PubMedCrossRef Parodi MB, Bandello F. Branch retinal vein occlusion: classification and treatment. Ophthalmologica. 2009;223:298–305.PubMedCrossRef
97.
Zurück zum Zitat Shahid H, Hossain P, Amoaku WM. The management of retinal vein occlusion: is interventional ophthalmology the way forward? Br J Ophthalmol. 2006;90:627–39.PubMedCrossRef Shahid H, Hossain P, Amoaku WM. The management of retinal vein occlusion: is interventional ophthalmology the way forward? Br J Ophthalmol. 2006;90:627–39.PubMedCrossRef
98.
Zurück zum Zitat Hughes S, Gardiner T, Baxter L, Chan-Ling T. Changes in pericytes and smooth muscle cells in the kitten model of retinopathy of prematurity: implications for plus disease. Invest Ophthalmol Vis Sci. 2007;48:1368–79.PubMedCrossRef Hughes S, Gardiner T, Baxter L, Chan-Ling T. Changes in pericytes and smooth muscle cells in the kitten model of retinopathy of prematurity: implications for plus disease. Invest Ophthalmol Vis Sci. 2007;48:1368–79.PubMedCrossRef
99.
Zurück zum Zitat Tendera M, Wojakowski W, Ruzyllo W, Chojnowska L, Kepka C, et al. Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J. 2009;30:1313–21.PubMedCrossRef Tendera M, Wojakowski W, Ruzyllo W, Chojnowska L, Kepka C, et al. Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J. 2009;30:1313–21.PubMedCrossRef
100.
Zurück zum Zitat Sekiguchi H, Ii M, Losordo DW. The relative potency and safety of endothelial progenitor cells and unselected mononuclear cells for recovery from myocardial infarction and ischemia. J Cell Physiol. 2009;219:235–42.PubMedCrossRef Sekiguchi H, Ii M, Losordo DW. The relative potency and safety of endothelial progenitor cells and unselected mononuclear cells for recovery from myocardial infarction and ischemia. J Cell Physiol. 2009;219:235–42.PubMedCrossRef
Metadaten
Titel
Cell-Based Therapies for Diabetic Retinopathy
verfasst von
Lynn C. Shaw
Matthew B. Neu
Maria B. Grant
Publikationsdatum
01.08.2011
Verlag
Current Science Inc.
Erschienen in
Current Diabetes Reports / Ausgabe 4/2011
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-011-0197-8

Weitere Artikel der Ausgabe 4/2011

Current Diabetes Reports 4/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.