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Fadini, Gian Paolo (2013) Bone marrow dysfunction in diabetes. [Tesi di dottorato]

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Abstract (inglese)

Background. Diabetes mellitus (DM) increases cardiovascular disease (CVD) and this is attributed, at least in part, to shortage of vascular regenerative cells derived from the bone marrow (BM). Indeed, the BM harbours several subsets of progenitor cells for endothelial, smooth muscle cells and cardiomyocytes, which derive from a common CD34+ ancestor. Recent data from experimental models of type 1 and type 2 diabetes highlight BM pathologies that include microangiopathy, neuropathy, altered gene expression and niche dysfunction.
Aims. The set of experiments herein described aim to portray the alterations of BM function in clinical and experimental diabetes.
Methods. The approaches are diversified and include: 1) A prospective trial of direct BM stimulation with human recombinant granulocyte colony stimulating factor (G-CSF) in diabetic and non diabetic patients; 2) A meta-regression analysis of trials using G-CSF to stimulate cardiovascular repair in diabetic and non diabetic patients; 3) A study of stem/progenitor cell compartmentalization in the BM and peripheral blood (PB), in relation to diabetes; 4) An animal study to dissect the role of DPP-4 dysregulation in the impaired stem/progenitor cell mobilization induced by diabetes.
Results. Part 1: in response to G-CSF, levels of CD34+ cells and other progenitor cell phenotypes increased in non DM subjects. DM patients had significantly impaired mobilization of CD34+, CD133+, CD34+CD133+ hematopoietic stem cells and CD133+KDR+ endothelial progenitors, independently of potential confounders. The in vivo angiogenic capacity of circulating mononuclear cells increased after hrG-CSF in non DM controls, but not in DM patients. DM was associated with inability to upregulate CD26/DPP-4 on CD34+ cells, which is required for the mobilizing effect of G-CSF.
Part 2: for the meta-regression analysis 227 articles were screened, 96 were retrieved for evaluation and 24 retained for the analysis of the primary end-point. There was a strong negative correlation between prevalence of diabetes and achieved CD34+ cell levels after G-CSF stimulation (r=-0.68; p<0.0001), while there was no correlation with other traditional risk factors. A multiple regression analysis showed that the correlation between diabetes and mobilization was independent. In 13 articles reporting pre- and post-G-CSF cell counts, the increase in CD34+ cells was also negatively correlated with prevalence of diabetes (r=-0.82; p<0.0001).
Part 3. PB and BM CD34+ cell counts were directly correlated, and that most circulating CD34+ cells were viable, non-proliferating and derived from the BM. Then, PB and BM CD34+ cell levels were analyzed in a 2-compartment model in 72 patients with or without cardiovascular disease. Self organizing maps showed that disturbed compartmentalization of CD34+ cells was associated with aging and cardiovascular risk factors, especially diabetes. High activity of DPP-4, a regulator of the mobilizing chemokine SDF-1α, was associated with altered stem cell compartmentalization. The role of DPP-4 in the BM mobilization response of diabetic rats was then assessed. Diabetes differentially affected DPP-4 activity in PB and BM and impaired stem/progenitor cell mobilization after ischemia or G-CSF administration. DPP-4 activity in the BM was required for the mobilizing effect of G-CSF, while in PB it blunted ischemia-induced mobilization. Indeed, DPP-4 deficiency restored ischemia (but not G-CSF) -induced stem cell mobilization and improved vascular recovery in diabetic animals.
Conclusion. Evidences from multiple clinical and experimental approaches indicate that diabetes impairs the mobilization of stem/progenitor cells from the BM to PB. This primary BM defect is related to a maladaptive and tissue-specific DPP-4 dysregulation

Abstract (italiano)

Presupposti. Il diabete mellito (DM) aumenta il rischio cardiovascolare e ciò viene attribuito almeno in parte alla riduzione delle cellule vasculo-rigenerative di origine midollare. Infatti il midollo osseo contiene precursori per cellule endoteliali, muscolari lisce e cardiomiociti, che derivano da un progenitore CD34+. Dati recenti ottenuti da modelli sperimentali di diabete tipo 1 e tipo 2 indicano l’esistenza di difetti midollari che includono microangiopatia, neuropatia, alterazione dell’espressione genica e disfunzione della nicchia staminale.
Obiettivi. Questo set di esperimenti ha avuto l’obiettivo di descrivere in dettaglio le alterazioni della funzione midollare nel diabete clinico e sperimentale.
Metodi. Gli approcci metodologici sono diversificati e comprendono: 1) un trial di stimolazione midollare diretta con G-CSF ricombinante umano in pazienti con e senza diabete; 2) un’analisi di meta-regressione dei trials in cui il G-CSF è stato somministrato per indurre rigenerazione cardiovascolare in pazienti con e senza diabete; 3) lo studio della compartimentalizzazione delle cellule staminali/progenitrici nel midollo e nel sangue periferico, in relazione al diabete; 4) un modello animale per la definizione del ruolo di DPP-4 nel difetto di mobilizzazione midollare associato al diabete.
Risultati. Parte 1: in risposta al G-CSF, le cellule CD34+ circolanti aumentavano significativamente nel paziente non diabetico, ma non nel diabetico, che mostrava anche una difettosa mobilizzazione di cellule ematopoietiche CD133+ e CD34+CD133+, nonché di cellule progenitrici endoteliali CD133+KDR+, indipendentemente dai possibili fattori confondenti. La capacità angiogenica in vivo delle cellule mononucleate aumentava significativamente dopo G-CSF nei soggetti diabetici ma non nei non diabetici, rispetto al basale. Il diabete risultava associato ad una incapacità di upregolare DPP-4 sulle cellule CD34+ in risposta al G-CSF.
Parte 2: per la meta-regressione sono stati individuati 227 articoli, recuperati 96 e trattenuti 24 per l’analisi primaria. È stata identificata una forte correlazione negativa tra prevalenza del diabete all’interno di ogni trial e livello delle cellule CD34+ raggiunte dopo mobilizzazione con G-CSF (r=-0.68; p<0.0001). Una analisi di regressione multipla ha confermato che il risultato era indipendente da possibili fattori confondenti. In 13 articoli contenenti dati sui livelli di cellule CD34+ pre- e post-G-CSF, la correlazione negativa tra prevalenza del diabete e mobilizzazione appariva ancora più stretta (r=-0.82; p<0.0001).
Parte 3: i livelli delle cellule CD34+ nel midollo e nel sangue periferico risultano essere direttamente correlati e la maggior parte delle cellule CD34+ erano di origine midollare, non proliferanti e non apoptotiche. Lo studio della compartimentalizzazione delle cellule CD34+ in 72 pazienti con e senza malattia cardiovascolare mediante l’uso delle mappe auto-organizzanti ha permesso di rilevare alterazioni della mobilizzazione in presenza di diabete ed elevato rischio cardiovascolare. Inoltre, un’elevata attività plasmatica di DPP-4 si associava ad alterata compartimentalizzazione delle cellule CD34+. In ratti diabetici rispetto ai controlli, l’attività di DPP-4 risultava significativamente aumentata nel sangue periferico e ridotta nel midollo osseo. Lo studio di ratti geneticamente deficienti dell’enzima DPP-4 ha permesso di stabilire che l’alterazione tessuto-specifica di DPP-4 nel diabete è responsabile del difetto di mobilizzazione post-G-CSF e post-ischemia. La delezione di DPP-4 ripristinava la mobilizzazione post-ischemica di cellule staminali ematopoietiche e progenitrici endoteliali e favoriva il recupero del tessuto ischemico nel diabete.
Conclusioni. Diversi tipi di evidenze sperimentali indicano chiaramente che il diabete induce un difetto nella mobilizzazione delle cellule staminali/progenitrici midollari. Questo difetto primitivo del midollo osseo nel diabete è correlato ad una disregolazione tessuto-specifica dell’attività dell’enzima DPP-4

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Tipo di EPrint:Tesi di dottorato
Relatore:Avogaro, Angelo
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > METODOLOGIA CLINICA, SCIENZE ENDOCRINOLOGICHE E DIABETOLOGICHE
Data di deposito della tesi:15 Gennaio 2013
Anno di Pubblicazione:15 Gennaio 2013
Parole chiave (italiano / inglese):Diabete / diabetes Midollo osseo / bone marrow Vasculopatia / vascular disease Ischemia / ischemia Angiogenesi / angiogenesis Dipeptidil-peptidase-4 / dipeptidyl-peptidase-4
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/11 Malattie dell'apparato cardiovascolare
Area 06 - Scienze mediche > MED/15 Malattie del sangue
Area 06 - Scienze mediche > MED/13 Endocrinologia
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Dipartimenti > Dipartimento di Medicina
Codice ID:5352
Depositato il:15 Ott 2013 09:09
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1. Fadini GP, Avogaro A: It is all in the blood: the multifaceted contribution of circulating progenitor cells in diabetic complications. Exp Diabetes Res 2012:742976, 2012 Cerca con Google

2. Fadini GP: An underlying principle for the study of circulating progenitor cells in diabetes and its complications. Diabetologia 51:1091-1094, 2008 Cerca con Google

3. Fadini GP, Sartore S, Agostini C, Avogaro A: Significance of endothelial progenitor cells in subjects with diabetes. Diabetes Care 30:1305-1313, 2007 Cerca con Google

4. Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A, Agostini C, Avogaro A: Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia 49:3075-3084, 2006 Cerca con Google

5. Oikawa A, Siragusa M, Quaini F, Mangialardi G, Katare RG, Caporali A, van Buul JD, van Alphen FP, Graiani G, Spinetti G, Kraenkel N, Prezioso L, Emanueli C, Madeddu P: Diabetes mellitus induces bone marrow microangiopathy. Arterioscler Thromb Vasc Biol 30:498-508, 2010 Cerca con Google

6. Busik JV, Tikhonenko M, Bhatwadekar A, Opreanu M, Yakubova N, Caballero S, Player D, Nakagawa T, Afzal A, Kielczewski J, Sochacki A, Hasty S, Li Calzi S, Kim S, Duclas SK, Segal MS, Guberski DL, Esselman WJ, Boulton ME, Grant MB: Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock. J Exp Med 206:2897-2906, 2009 Cerca con Google

7. Orlandi A, Chavakis E, Seeger F, Tjwa M, Zeiher AM, Dimmeler S: Long-term diabetes impairs repopulation of hematopoietic progenitor cells and dysregulates the cytokine expression in the bone marrow microenvironment in mice. Basic Res Cardiol 105:703-712, 2010 Cerca con Google

8. Ferraro F, Lymperi S, Mendez-Ferrer S, Saez B, Spencer JA, Yeap BY, Masselli E, Graiani G, Prezioso L, Rizzini EL, Mangoni M, Rizzoli V, Sykes SM, Lin CP, Frenette PS, Quaini F, Scadden DT: Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci Transl Med 3:104ra101, 2011 Cerca con Google

9. DiPersio JF: Diabetic stem-cell "mobilopathy". N Engl J Med 365:2536-2538, 2011 Cerca con Google

10. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM: Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964-967, 1997 Cerca con Google

11. Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z: Transdifferentiation of human peripheral blood CD34+-enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 108:2070-2073, 2003 Cerca con Google

12. Fadini GP, Losordo D, Dimmeler S: Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circ Res 110:624-637, 2012 Cerca con Google

13. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T: Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434-438, 1999 Cerca con Google

14. Iekushi K, Seeger F, Assmus B, Zeiher AM, Dimmeler S: Regulation of Cardiac MicroRNAs by Bone Marrow Mononuclear Cell Therapy in Myocardial Infarction. Circulation 125:1765-1773, 2012 Cerca con Google

15. Ohtani K, Dimmeler S: Control of cardiovascular differentiation by microRNAs. Basic Res Cardiol 106:5-11, 2011 Cerca con Google

16. Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, Zeiher AM, Dimmeler S: Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol 39:733-742, 2005 Cerca con Google

17. Wu J, Li J, Zhang N, Zhang C: Stem cell-based therapies in ischemic heart diseases: a focus on aspects of microcirculation and inflammation. Basic Res Cardiol 106:317-324, 2011 Cerca con Google

18. Assmus B, Iwasaki M, Schachinger V, Roexe T, Koyanagi M, Iekushi K, Xu Q, Tonn T, Seifried E, Liebner S, Kranert WT, Grunwald F, Dimmeler S, Zeiher AM: Acute myocardial infarction activates progenitor cells and increases Wnt signalling in the bone marrow. Eur Heart J, 2011 Cerca con Google

19. Werner N, Nickenig G: Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy? Arterioscler Thromb Vasc Biol 26:257-266, 2006 Cerca con Google

20. Fadini GP, Agostini C, Sartore S, Avogaro A: Endothelial progenitor cells in the natural history of atherosclerosis. Atherosclerosis 194:46-54, 2007 Cerca con Google

21. Fadini GP, Maruyama S, Ozaki T, Taguchi A, Meigs J, Dimmeler S, Zeiher AM, de Kreutzenberg S, Avogaro A, Nickenig G, Schmidt-Lucke C, Werner N: Circulating progenitor cell count for cardiovascular risk stratification: a pooled analysis. PLoS One 5:e11488, 2010 Cerca con Google

22. Chavakis E, Koyanagi M, Dimmeler S: Enhancing the outcome of cell therapy for cardiac repair: progress from bench to bedside and back. Circulation 121:325-335, 2010 Cerca con Google

23. Zohlnhofer D, Dibra A, Koppara T, de Waha A, Ripa RS, Kastrup J, Valgimigli M, Schomig A, Kastrati A: Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis. J Am Coll Cardiol 51:1429-1437, 2008 Cerca con Google

24. Fadini GP, Boscaro E, de Kreutzenberg S, Agostini C, Seeger F, Dimmeler S, Zeiher A, Tiengo A, Avogaro A: Time course and mechanisms of circulating progenitor cell reduction in the natural history of type 2 diabetes. Diabetes Care 33:1097-1102, 2010 Cerca con Google

25. Roberts AW: G-CSF: a key regulator of neutrophil production, but that's not all! Growth Factors 23:33-41, 2005 Cerca con Google

26. Fadini GP, Albiero M, Menegazzo L, de Kreutzenberg SV, Avogaro A: The increased dipeptidyl peptidase-4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin-treated patients. Diabetes Obes Metab 14:518-522, 2012 Cerca con Google

27. Fadini GP: Is bone marrow another target of diabetic complications? Eur J Clin Invest 41:457-463, 2011 Cerca con Google

28. van Der Auwera P, Platzer E, Xu ZX, Schulz R, Feugeas O, Capdeville R, Edwards DJ: Pharmacodynamics and pharmacokinetics of single doses of subcutaneous pegylated human G-CSF mutant (Ro 25-8315) in healthy volunteers: comparison with single and multiple daily doses of filgrastim. Am J Hematol 66:245-251, 2001 Cerca con Google

29. Fadini GP, de Kreutzenberg SV, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A: Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J 27:2247-2255, 2006 Cerca con Google

30. Rehman J, Li J, Orschell CM, March KL: Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 107:1164-1169, 2003 Cerca con Google

31. Pucci F, Venneri MA, Biziato D, Nonis A, Moi D, Sica A, Di Serio C, Naldini L, De Palma M: A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships. Blood 114:901-914, 2009 Cerca con Google

32. Christopherson KW, 2nd, Uralil SE, Porecha NK, Zabriskie RC, Kidd SM, Ramin SM: G-CSF- and GM-CSF-induced upregulation of CD26 peptidase downregulates the functional chemotactic response of CD34+CD38- human cord blood hematopoietic cells. Exp Hematol 34:1060-1068, 2006 Cerca con Google

33. Tepper OM, Carr J, Allen RJ, Jr., Chang CC, Lin CD, Tanaka R, Gupta SM, Levine JP, Saadeh PB, Warren SM: Decreased circulating progenitor cell number and failed mechanisms of stromal cell-derived factor-1alpha mediated bone marrow mobilization impair diabetic tissue repair. Diabetes 59:1974-1983, 2010 Cerca con Google

34. Christopherson KW, 2nd, Cooper S, Broxmeyer HE: Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells. Blood 101:4680-4686, 2003 Cerca con Google

35. Nishimura Y, Ii M, Qin G, Hamada H, Asai J, Takenaka H, Sekiguchi H, Renault MA, Jujo K, Katoh N, Kishimoto S, Ito A, Kamide C, Kenny J, Millay M, Misener S, Thorne T, Losordo DW: CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice. J Invest Dermatol 132:711-720, 2012 Cerca con Google

36. Fiorina P, Jurewicz M, Vergani A, Petrelli A, Carvello M, D'Addio F, Godwin JG, Law K, Wu E, Tian Z, Thoma G, Kovarik J, La Rosa S, Capella C, Rodig S, Zerwes HG, Sayegh MH, Abdi R: Targeting the CXCR4-CXCL12 axis mobilizes autologous hematopoietic stem cells and prolongs islet allograft survival via programmed death ligand 1. J Immunol 186:121-131, 2011 Cerca con Google

37. Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M: Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest 108:1341-1348, 2001 Cerca con Google

38. Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeler S: Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 9:1370-1376, 2003 Cerca con Google

39. de Resende MM, Huw LY, Qian HS, Kauser K: Role of endothelial nitric oxide in bone marrow-derived progenitor cell mobilization. Handb Exp Pharmacol:37-44, 2007 Cerca con Google

40. Fadini GP, Boscaro E, Albiero M, Menegazzo L, Frison V, de Kreutzenberg S, Agostini C, Tiengo A, Avogaro A: The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care 33:1607-1609, 2010 Cerca con Google

41. Boodhwani M, Sodha NR, Mieno S, Xu SH, Feng J, Ramlawi B, Clements RT, Sellke FW: Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes. Circulation 116:I31-37, 2007 Cerca con Google

42. Caporali A, Meloni M, Vollenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, Agami R, le Sage C, Condorelli G, Madeddu P, Martelli F, Emanueli C: Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation 123:282-291, 2011 Cerca con Google

43. Loomans CJ, de Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, de Boer HC, Verhaar MC, Braam B, Rabelink TJ, van Zonneveld AJ: Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 53:195-199, 2004 Cerca con Google

44. Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC: Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106:2781-2786, 2002 Cerca con Google

45. Fadini GP, Agostini C, Avogaro A: Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis 209:10-17, 2010 Cerca con Google

46. Higgins JPT, Green S, (Editors): Assessment of study quality. Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 [updated September 2006]. The Cochrane Library Issue 4 Chichester, UK: John Wiley & Sons, Ltd; , 2006 Cerca con Google

47. Thompson SG, Higgins JP: How should meta-regression analyses be undertaken and interpreted? Stat Med 21:1559-1573, 2002 Cerca con Google

48. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700, 2009 Cerca con Google

49. Burt RK, Testori A, Oyama Y, Rodriguez HE, Yaung K, Villa M, Bucha JM, Milanetti F, Sheehan J, Rajamannan N, Pearce WH: Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia. Bone Marrow Transplant 45:111-116, 2010 Cerca con Google

50. Onodera R, Teramukai S, Tanaka S, Kojima S, Horie T, Matoba S, Murohara T, Matsubara H, Fukushima M: Bone marrow mononuclear cells versus G-CSF-mobilized peripheral blood mononuclear cells for treatment of lower limb ASO: pooled analysis for long-term prognosis. Bone Marrow Transplant 46:278-284, 2011 Cerca con Google

51. Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B: Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation 126:551-568, 2012 Cerca con Google

52. Clifford DM, Fisher SA, Brunskill SJ, Doree C, Mathur A, Watt S, Martin-Rendon E: Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev 2:CD006536, 2012 Cerca con Google

53. Leone AM, Rutella S, Bonanno G, Abbate A, Rebuzzi AG, Giovannini S, Lombardi M, Galiuto L, Liuzzo G, Andreotti F, Lanza GA, Contemi AM, Leone G, Crea F: Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function. Eur Heart J 26:1196-1204, 2005 Cerca con Google

54. Leone AM, Rutella S, Bonanno G, Contemi AM, de Ritis DG, Giannico MB, Rebuzzi AG, Leone G, Crea F: Endogenous G-CSF and CD34+ cell mobilization after acute myocardial infarction. Int J Cardiol 111:202-208, 2006 Cerca con Google

55. Fadini GP, Albiero M, Menegazzo L, de Kreutzenberg SV, Avogaro A: The increased dipeptidyl peptidase-4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin-treated patients. Diabetes Obes Metab, 2011 Cerca con Google

56. Bolego C, Rossoni G, Fadini GP, Vegeto E, Pinna C, Albiero M, Boscaro E, Agostini C, Avogaro A, Gaion RM, Cignarella A: Selective estrogen receptor-alpha agonist provides widespread heart and vascular protection with enhanced endothelial progenitor cell mobilization in the absence of uterotrophic action. FASEB J 24:2262-2272, 2010 Cerca con Google

57. Kohonen T: Self-Organizing Maps. Springer-Verlag Heidelberg, 2000 Cerca con Google

58. Bertolini F, Shaked Y, Mancuso P, Kerbel RS: The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 6:835-845, 2006 Cerca con Google

59. Angelini A, Castellani C, Tona F, Gambino A, Caforio AP, Feltrin G, Della Barbera M, Valente M, Gerosa G, Thiene G: Continuous engraftment and differentiation of male recipient Y-chromosome-positive cardiomyocytes in donor female human heart transplants. J Heart Lung Transplant 26:1110-1118, 2007 Cerca con Google

60. Sorrentino SA, Doerries C, Manes C, Speer T, Dessy C, Lobysheva I, Mohmand W, Akbar R, Bahlmann F, Besler C, Schaefer A, Hilfiker-Kleiner D, Luscher TF, Balligand JL, Drexler H, Landmesser U: Nebivolol exerts beneficial effects on endothelial function, early endothelial progenitor cells, myocardial neovascularization, and left ventricular dysfunction early after myocardial infarction beyond conventional beta1-blockade. J Am Coll Cardiol 57:601-611, 2011 Cerca con Google

61. Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP, Gurtner GC: Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10:858-864, 2004 Cerca con Google

62. Zaruba MM, Theiss HD, Vallaster M, Mehl U, Brunner S, David R, Fischer R, Krieg L, Hirsch E, Huber B, Nathan P, Israel L, Imhof A, Herbach N, Assmann G, Wanke R, Mueller-Hoecker J, Steinbeck G, Franz WM: Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction. Cell Stem Cell 4:313-323, 2009 Cerca con Google

63. Fadini GP, Avogaro A: Cardiovascular effects of DPP-4 inhibition: Beyond GLP-1. Vascul Pharmacol 55:10-16, 2011 Cerca con Google

64. Christopherson KW, Cooper S, Hangoc G, Broxmeyer HE: CD26 is essential for normal G-CSF-induced progenitor cell mobilization as determined by CD26-/- mice. Exp Hematol 31:1126-1134, 2003 Cerca con Google

65. Albiero M, Menegazzo L, Boscaro E, Agostini C, Avogaro A, Fadini GP: Defective recruitment, survival and proliferation of bone marrow-derived progenitor cells at sites of delayed diabetic wound healing in mice. Diabetologia 54:945-953, 2011 Cerca con Google

66. Dong L, Kang L, Ding L, Chen Q, Bai J, Gu R, Li L, Xu B: Insulin modulates ischemia-induced endothelial progenitor cell mobilization and neovascularization in diabetic mice. Microvasc Res 82:227-236, 2011 Cerca con Google

67. Sanganalmath SK, Abdel-Latif A, Bolli R, Xuan YT, Dawn B: Hematopoietic cytokines for cardiac repair: mobilization of bone marrow cells and beyond. Basic Res Cardiol 106:709-733, 2011 Cerca con Google

68. Broxmeyer HE, Hoggatt J, O'Leary HA, Mantel C, Chitteti BR, Cooper S, Messina-Graham S, Hangoc G, Farag S, Rohrabaugh SL, Ou X, Speth J, Pelus LM, Srour EF, Campbell TB: Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis. Nat Med, 2012 Cerca con Google

69. Achilli F, Malafronte C, Lenatti L, Gentile F, Dadone V, Gibelli G, Maggiolini S, Squadroni L, Di Leo C, Burba I, Pesce M, Mircoli L, Capogrossi MC, Di Lelio A, Camisasca P, Morabito A, Colombo G, Pompilio G: Granulocyte colony-stimulating factor attenuates left ventricular remodelling after acute anterior STEMI: results of the single-blind, randomized, placebo-controlled multicentre STem cEll Mobilization in Acute Myocardial Infarction (STEM-AMI) Trial. Eur J Heart Fail 12:1111-1121, 2010 Cerca con Google

70. Arai M, Misao Y, Nagai H, Kawasaki M, Nagashima K, Suzuki K, Tsuchiya K, Otsuka S, Uno Y, Takemura G, Nishigaki K, Minatoguchi S, Fujiwara H: Granulocyte colony-stimulating factor: a noninvasive regeneration therapy for treating atherosclerotic peripheral artery disease. Circ J 70:1093-1098, 2006 Cerca con Google

71. Boyle AJ, Whitbourn R, Schlicht S, Krum H, Kocher A, Nandurkar H, Bergmann S, Daniell M, O'Day J, Skerrett D, Haylock D, Gilbert RE, Itescu S: Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: a 12-month follow-up. Int J Cardiol 109:21-27, 2006 Cerca con Google

72. Chih S, Macdonald PS, McCrohon JA, Ma D, Moore J, Feneley MP, Law M, Kovacic JC, Graham RM: Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial. Heart 98:282-290, 2012 Cerca con Google

73. Ellis SG, Penn MS, Bolwell B, Garcia M, Chacko M, Wang T, Brezina KJ, McConnell G, Topol EJ: Granulocyte colony stimulating factor in patients with large acute myocardial infarction: results of a pilot dose-escalation randomized trial. Am Heart J 152:1051 e1059-1014, 2006 Cerca con Google

74. Engelmann MG, Theiss HD, Hennig-Theiss C, Huber A, Wintersperger BJ, Werle-Ruedinger AE, Schoenberg SO, Steinbeck G, Franz WM: Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial. J Am Coll Cardiol 48:1712-1721, 2006 Cerca con Google

75. Huttmann A, Duhrsen U, Stypmann J, Noppeney R, Nuckel H, Neumann T, Gutersohn A, Nikol S, Erbel R: Granulocyte colony-stimulating factor-induced blood stem cell mobilisation in patients with chronic heart failure--Feasibility, safety and effects on exercise tolerance and cardiac function. Basic Res Cardiol 101:78-86, 2006 Cerca con Google

76. Ince H, Petzsch M, Kleine HD, Eckard H, Rehders T, Burska D, Kische S, Freund M, Nienaber CA: Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: final 1-year results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial. Circulation 112:I73-80, 2005 Cerca con Google

77. Ince H, Petzsch M, Kleine HD, Schmidt H, Rehders T, Korber T, Schumichen C, Freund M, Nienaber CA: Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI). Circulation 112:3097-3106, 2005 Cerca con Google

78. Karimabad HM, Shabestari M, Baharvand H, Vosough A, Gourabi H, Shahverdi A, Shamsian A, Abdolhoseini S, Moazzami K, Marjanimehr MM, Emami F, Bidkhori HR, Hamedanchi A, Talebi S, Farrokhi F, Jabbari-Azad F, Fadavi M, Garivani U, Mahmoodi M, Aghdami N: Lack of beneficial effects of granulocyte colony-stimulating factor in patients with subacute myocardial infarction undergoing late revascularization: a double-blind, randomized, placebo-controlled clinical trial. Acta Cardiol 66:219-224, 2011 Cerca con Google

79. Kuethe F, Figulla HR, Herzau M, Voth M, Fritzenwanger M, Opfermann T, Pachmann K, Krack A, Sayer HG, Gottschild D, Werner GS: Treatment with granulocyte colony-stimulating factor for mobilization of bone marrow cells in patients with acute myocardial infarction. Am Heart J 150:115, 2005 Cerca con Google

80. Kovacic JC, Macdonald P, Feneley MP, Muller DW, Freund J, Dodds A, Milliken S, Tao H, Itescu S, Moore J, Ma D, Graham RM: Safety and efficacy of consecutive cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: the G-CSF in angina patients with IHD to stimulate neovascularization (GAIN I) trial. Am Heart J 156:954-963, 2008 Cerca con Google

81. Leone AM, Galiuto L, Garramone B, Rutella S, Giannico MB, Brugaletta S, Perfetti M, Liuzzo G, Porto I, Burzotta F, Niccoli G, Biasucci LM, Leone G, Rebuzzi AG, Crea F: Usefulness of granulocyte colony-stimulating factor in patients with a large anterior wall acute myocardial infarction to prevent left ventricular remodeling (the rigenera study). Am J Cardiol 100:397-403, 2007 Cerca con Google

82. Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M, Poh KK, Weinstein R, Kearney M, Chaudhry M, Burg A, Eaton L, Heyd L, Thorne T, Shturman L, Hoffmeister P, Story K, Zak V, Dowling D, Traverse JH, Olson RE, Flanagan J, Sodano D, Murayama T, Kawamoto A, Kusano KF, Wollins J, Welt F, Shah P, Soukas P, Asahara T, Henry TD: Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 115:3165-3172, 2007 Cerca con Google

83. Ripa RS, Haack-Sorensen M, Wang Y, Jorgensen E, Mortensen S, Bindslev L, Friis T, Kastrup J: Bone marrow derived mesenchymal cell mobilization by granulocyte-colony stimulating factor after acute myocardial infarction: results from the Stem Cells in Myocardial Infarction (STEMMI) trial. Circulation 116:I24-30, 2007 Cerca con Google

84. Ripa RS, Wang Y, Jorgensen E, Johnsen HE, Hesse B, Kastrup J: Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease. Eur Heart J 27:1785-1792, 2006 Cerca con Google

85. Sprigg N, Bath PM, Zhao L, Willmot MR, Gray LJ, Walker MF, Dennis MS, Russell N: Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem cell Trial of recovery EnhanceMent after Stroke (STEMS) pilot randomized, controlled trial (ISRCTN 16784092). Stroke 37:2979-2983, 2006 Cerca con Google

86. Stein A, Zohlnhofer D, Pogatsa-Murray G, von Wedel J, Steppich BA, Schomig A, Kastrati A, Ott I: Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction. Thromb Haemost 103:638-643, 2010 Cerca con Google

87. Suzuki K, Nagashima K, Arai M, Uno Y, Misao Y, Takemura G, Nishigaki K, Minatoguchi S, Watanabe S, Tei C, Fujiwara H: Effect of granulocyte colony-stimulating factor treatment at a low dose but for a long duration in patients with coronary heart disease. Circ J 70:430-437, 2006 Cerca con Google

88. Takano H, Hasegawa H, Kuwabara Y, Nakayama T, Matsuno K, Miyazaki Y, Yamamoto M, Fujimoto Y, Okada H, Okubo S, Fujita M, Shindo S, Kobayashi Y, Komiyama N, Takekoshi N, Imai K, Himi T, Ishibashi I, Komuro I: Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction. Int J Cardiol 122:41-47, 2007 Cerca con Google

89. Valgimigli M, Rigolin GM, Cittanti C, Malagutti P, Curello S, Percoco G, Bugli AM, Della Porta M, Bragotti LZ, Ansani L, Mauro E, Lanfranchi A, Giganti M, Feggi L, Castoldi G, Ferrari R: Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile. Eur Heart J 26:1838-1845, 2005 Cerca con Google

90. Wang S, Cui J, Peng W, Lu M: Intracoronary autologous CD34+ stem cell therapy for intractable angina. Cardiology 117:140-147, 2010 Cerca con Google

91. Wolfram O, Jentsch-Ullrich K, Wagner A, Hammwohner M, Steinke R, Franke A, Zupan I, Klein HU, Goette A: G-CSF-induced mobilization of CD34(+) progenitor cells and proarrhythmic effects in patients with severe coronary artery disease. Pacing Clin Electrophysiol 30 Suppl 1:S166-169, 2007 Cerca con Google

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