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Volumn 1, Issue 4, 2013, Pages 533-540

Vascular regenerative therapies for the treatment of erectile dysfunction: Current approaches

Author keywords

Endothelial progenitor cells; Erectile dysfunction; Vascular regenerative therapy

Indexed keywords

BIOLOGICAL MARKER; CD133 ANTIGEN; CD34 ANTIGEN; CYCLIC GMP; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FIBROBLAST GROWTH FACTOR 2; LARGE CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL; MELATONIN; NITRIC OXIDE SYNTHASE; PHOSPHODIESTERASE V INHIBITOR; REACTIVE OXYGEN METABOLITE; RETROVIRUS VECTOR; SUPEROXIDE; TADALAFIL; VARDENAFIL; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; VASCULOTROPIN RECEPTOR 2;

EID: 84879496815     PISSN: 20472919     EISSN: 20472927     Source Type: Journal    
DOI: 10.1111/j.2047-2927.2013.00087.x     Document Type: Review
Times cited : (25)

References (43)
  • 2
    • 33847711835 scopus 로고    scopus 로고
    • Mesenchymalstem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction
    • Bivalacqua TJ, Deng W, Kendirci M, Usta MF, Robinson C, Taylor BK et al. (2007) Mesenchymalstem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am J Physiol Heart Circ Physiol 292, 1278-1290.
    • (2007) Am J Physiol Heart Circ Physiol , vol.292 , pp. 1278-1290
    • Bivalacqua, T.J.1    Deng, W.2    Kendirci, M.3    Usta, M.F.4    Robinson, C.5    Taylor, B.K.6
  • 3
    • 0032919721 scopus 로고    scopus 로고
    • Expression of messenger ribonucleic acid splice variants for vascular endothelial growth factor in the penis of adult rats and humans
    • Burchardt M, Burchardt T, Chen MW, Shabsigh A, de la Taille A, Buttyan R et al. (1999) Expression of messenger ribonucleic acid splice variants for vascular endothelial growth factor in the penis of adult rats and humans. Biol Reprod 60, 398-404.
    • (1999) Biol Reprod , vol.60 , pp. 398-404
    • Burchardt, M.1    Burchardt, T.2    Chen, M.W.3    Shabsigh, A.4    de la Taille, A.5    Buttyan, R.6
  • 4
    • 36248932643 scopus 로고    scopus 로고
    • Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing
    • Chamberlain G, Fox J, Ashton B & Middleton J. (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25, 2739-2749.
    • (2007) Stem Cells , vol.25 , pp. 2739-2749
    • Chamberlain, G.1    Fox, J.2    Ashton, B.3    Middleton, J.4
  • 5
    • 70350571204 scopus 로고    scopus 로고
    • Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys
    • Christ GJ, Andersson KE, Williams K, Zhao W, D'Agostino R Jr, Kaplan J et al. (2009) Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys. Eur Urol 56, 1055-1066.
    • (2009) Eur Urol , vol.56 , pp. 1055-1066
    • Christ, G.J.1    Andersson, K.E.2    Williams, K.3    Zhao, W.4    D'Agostino Jr, R.5    Kaplan, J.6
  • 6
    • 84874410566 scopus 로고    scopus 로고
    • Arterial erectile dysfunction and peripheral arterial disease: reliability of a new phenotype of endothelial progenitor cells and endothelial microparticles
    • Condorelli RA, Calogero AE, Vicari E, di Pino L, Giacone F, Mongioì L et al. (2012) Arterial erectile dysfunction and peripheral arterial disease: reliability of a new phenotype of endothelial progenitor cells and endothelial microparticles. J Androl 33, 1268-1275.
    • (2012) J Androl , vol.33 , pp. 1268-1275
    • Condorelli, R.A.1    Calogero, A.E.2    Vicari, E.3    di Pino, L.4    Giacone, F.5    Mongioì, L.6
  • 7
    • 84875223304 scopus 로고    scopus 로고
    • Arterial erectile dysfunction: different severities of endothelial apoptosis between diabetic patients "responders" and "non responders" to sildenafil
    • doi:pii: S0953-6205(13)00003-4.
    • Condorelli RA, Calogero AE, Favilla V, Morgia G, Johnson EO, Castiglione R et al. (2013) Arterial erectile dysfunction: different severities of endothelial apoptosis between diabetic patients "responders" and "non responders" to sildenafil. Eur J Intern Med 24, 234-240. doi:pii: S0953-6205(13)00003-4.
    • (2013) Eur J Intern Med , vol.24 , pp. 234-240
    • Condorelli, R.A.1    Calogero, A.E.2    Favilla, V.3    Morgia, G.4    Johnson, E.O.5    Castiglione, R.6
  • 10
    • 70449713762 scopus 로고    scopus 로고
    • Sildenafil increases endothelial progenitor cell function and improves ischemia-induced neovascularization in hypercholesterolemic apolipoprotein E-deficient mice
    • Dussault S, Maingrette F, Ménard C, Michaud SE, Haddad P, Groleau J et al. (2009) Sildenafil increases endothelial progenitor cell function and improves ischemia-induced neovascularization in hypercholesterolemic apolipoprotein E-deficient mice. Hypertension 54, 1043-1049.
    • (2009) Hypertension , vol.54 , pp. 1043-1049
    • Dussault, S.1    Maingrette, F.2    Ménard, C.3    Michaud, S.E.4    Haddad, P.5    Groleau, J.6
  • 11
  • 12
    • 33748291505 scopus 로고    scopus 로고
    • Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction
    • Foresta C, Ferlin A, De Toni L, Lana A, Vinanzi C, Galan A et al. (2006) Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction. Int J Impot Res 18, 484-488.
    • (2006) Int J Impot Res , vol.18 , pp. 484-488
    • Foresta, C.1    Ferlin, A.2    De Toni, L.3    Lana, A.4    Vinanzi, C.5    Galan, A.6
  • 13
    • 33947198649 scopus 로고    scopus 로고
    • Relationship between vascular damage degrees and endothelial progenitor cells in patients with erectile dysfunction: effect of vardenafil administration and PDE5 expression in the bone marrow
    • Foresta C, Caretta N, Lana A, De Toni L, Biagioli A, Vinanzi C et al. (2007) Relationship between vascular damage degrees and endothelial progenitor cells in patients with erectile dysfunction: effect of vardenafil administration and PDE5 expression in the bone marrow. Eur Urol 51, 1411-1417.
    • (2007) Eur Urol , vol.51 , pp. 1411-1417
    • Foresta, C.1    Caretta, N.2    Lana, A.3    De Toni, L.4    Biagioli, A.5    Vinanzi, C.6
  • 14
    • 74049113244 scopus 로고    scopus 로고
    • Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells
    • Garcia MM, Fandel TM, Lin G, Shindel AW, Banie L, Lin CS et al. (2010) Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. J Sex Med 7, 89-98.
    • (2010) J Sex Med , vol.7 , pp. 89-98
    • Garcia, M.M.1    Fandel, T.M.2    Lin, G.3    Shindel, A.W.4    Banie, L.5    Lin, C.S.6
  • 15
    • 0037376430 scopus 로고    scopus 로고
    • The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophicfactor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia
    • Gholami SS, Rogers R, Chang J, Ho HC, Grazziottin T, Lin CS et al. (2003) The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophicfactor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. J Urol 169, 1577-1581.
    • (2003) J Urol , vol.169 , pp. 1577-1581
    • Gholami, S.S.1    Rogers, R.2    Chang, J.3    Ho, H.C.4    Grazziottin, T.5    Lin, C.S.6
  • 16
    • 79952430861 scopus 로고    scopus 로고
    • Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats
    • Gou X, He WY, Xiao MZ, Qiu M, Wang M, Deng YZ et al. (2011) Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats. Asian J Androl 13, 332-338.
    • (2011) Asian J Androl , vol.13 , pp. 332-338
    • Gou, X.1    He, W.Y.2    Xiao, M.Z.3    Qiu, M.4    Wang, M.5    Deng, Y.Z.6
  • 18
    • 77949424323 scopus 로고    scopus 로고
    • Emerging gene and stem cell therapies for the treatment of erectile dysfunction
    • Harraz A, Shindel AW & Lue TF. (2010) Emerging gene and stem cell therapies for the treatment of erectile dysfunction. Nat Rev Urol 7, 143-152.
    • (2010) Nat Rev Urol , vol.7 , pp. 143-152
    • Harraz, A.1    Shindel, A.W.2    Lue, T.F.3
  • 19
    • 77955242336 scopus 로고    scopus 로고
    • The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model
    • Huang YC, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM et al. (2010) The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med 7, 1391-1400.
    • (2010) J Sex Med , vol.7 , pp. 1391-1400
    • Huang, Y.C.1    Ning, H.2    Shindel, A.W.3    Fandel, T.M.4    Lin, G.5    Harraz, A.M.6
  • 20
    • 38649108162 scopus 로고    scopus 로고
    • Human bone marrow mesenchymal stem cells in vivo
    • Jones E & McGonagle D. (2008) Human bone marrow mesenchymal stem cells in vivo. Rheumatology 47, 126-131.
    • (2008) Rheumatology , vol.47 , pp. 126-131
    • Jones, E.1    McGonagle, D.2
  • 21
    • 21344455539 scopus 로고    scopus 로고
    • Gene therapy for erectile dysfunction
    • Kendirci M, Gur S & Sikka SC. (2005) Gene therapy for erectile dysfunction. Front Biosci 10, 2758-2769.
    • (2005) Front Biosci , vol.10 , pp. 2758-2769
    • Kendirci, M.1    Gur, S.2    Sikka, S.C.3
  • 22
    • 84856950636 scopus 로고    scopus 로고
    • Circulating endothelial progenitor cells and endothelial microparticles in patients with arterial erectile dysfunction and metabolic syndrome
    • La Vignera S, Condorelli R, Vicari E, D'Agata R & Calogero AE. (2012) Circulating endothelial progenitor cells and endothelial microparticles in patients with arterial erectile dysfunction and metabolic syndrome. J Androl 33, 202-209.
    • (2012) J Androl , vol.33 , pp. 202-209
    • La Vignera, S.1    Condorelli, R.2    Vicari, E.3    D'Agata, R.4    Calogero, A.E.5
  • 23
    • 84884590991 scopus 로고    scopus 로고
    • VEGF genetic polymorphisms affect the responsiveness to sildenafil in clinical and postoperative erectile dysfunction
    • doi: 10.1038/tpj.2012.39 [Epub ahead of print].
    • Lacchini R, Muniz JJ, Nobre YT, Cologna AJ, Martins AC & Tanus-Santos JE. (2012) VEGF genetic polymorphisms affect the responsiveness to sildenafil in clinical and postoperative erectile dysfunction. Pharmacogenomics J doi: 10.1038/tpj.2012.39 [Epub ahead of print].
    • (2012) Pharmacogenomics J
    • Lacchini, R.1    Muniz, J.J.2    Nobre, Y.T.3    Cologna, A.J.4    Martins, A.C.5    Tanus-Santos, J.E.6
  • 24
    • 61849129485 scopus 로고    scopus 로고
    • Potential of adipose-derived stem cells for treatment of erectile dysfunction
    • Lin G, Banie L, Ning H, Bella AJ, Lin CS & Lue TF. (2009) Potential of adipose-derived stem cells for treatment of erectile dysfunction. J Sex Med 6, 320-327.
    • (2009) J Sex Med , vol.6 , pp. 320-327
    • Lin, G.1    Banie, L.2    Ning, H.3    Bella, A.J.4    Lin, C.S.5    Lue, T.F.6
  • 25
    • 33845774784 scopus 로고    scopus 로고
    • hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial
    • Melman A, Bar-Chama N, McCullough A, Davies K & Christ G. (2006) hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial. Hum Gene Ther 17, 1165-1176.
    • (2006) Hum Gene Ther , vol.17 , pp. 1165-1176
    • Melman, A.1    Bar-Chama, N.2    McCullough, A.3    Davies, K.4    Christ, G.5
  • 26
    • 63849294906 scopus 로고    scopus 로고
    • Fibroblast growth factor 2 promotes endothelial differentiation of adipose tissue-derived stem cells
    • Ning H, Liu G, Lin G, Yang R, Lue TF & Lin CS. (2009) Fibroblast growth factor 2 promotes endothelial differentiation of adipose tissue-derived stem cells. J Sex Med 6, 967-979.
    • (2009) J Sex Med , vol.6 , pp. 967-979
    • Ning, H.1    Liu, G.2    Lin, G.3    Yang, R.4    Lue, T.F.5    Lin, C.S.6
  • 27
    • 84856554173 scopus 로고    scopus 로고
    • Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration oferectile function in diabetic rats
    • Nishimatsu H, Suzuki E, Kumano S, Nomiya A, Liu M, Kume H et al. (2012) Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration oferectile function in diabetic rats. J Sex Med 9, 482-493.
    • (2012) J Sex Med , vol.9 , pp. 482-493
    • Nishimatsu, H.1    Suzuki, E.2    Kumano, S.3    Nomiya, A.4    Liu, M.5    Kume, H.6
  • 28
    • 84861825247 scopus 로고    scopus 로고
    • Scaffoldless tissue engineering of stem cell derived cavernous tissue for treatment of erectile function
    • Orabi H, Lin G, Ferretti L, Lin CS & Lue TF. (2012) Scaffoldless tissue engineering of stem cell derived cavernous tissue for treatment of erectile function. J Sex Med 9, 1522-1534.
    • (2012) J Sex Med , vol.9 , pp. 1522-1534
    • Orabi, H.1    Lin, G.2    Ferretti, L.3    Lin, C.S.4    Lue, T.F.5
  • 29
    • 84864501990 scopus 로고    scopus 로고
    • Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury
    • doi: 10.1111/j.1743-6109.2012.02760.x [Epub ahead of print].
    • Piao S, Kim IG, Lee JY, Hong SH, Kim SW, Hwang TK et al. (2012) Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury. J Sex Med doi: 10.1111/j.1743-6109.2012.02760.x [Epub ahead of print].
    • (2012) J Sex Med
    • Piao, S.1    Kim, I.G.2    Lee, J.Y.3    Hong, S.H.4    Kim, S.W.5    Hwang, T.K.6
  • 30
    • 79551487645 scopus 로고    scopus 로고
    • Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats
    • Qiu X, Lin H, Wang Y, Yu W, Chen Y, Wang R et al. (2011) Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med 8, 427-436.
    • (2011) J Sex Med , vol.8 , pp. 427-436
    • Qiu, X.1    Lin, H.2    Wang, Y.3    Yu, W.4    Chen, Y.5    Wang, R.6
  • 31
    • 84863504632 scopus 로고    scopus 로고
    • Effects of intravenous injection of adipose-derived stem cells in a rat model of radiation therapy-induced erectile dysfunction
    • Qiu X, Villalta J, Ferretti L, Fandel TM, Albersen M, Lin G et al. (2012a) Effects of intravenous injection of adipose-derived stem cells in a rat model of radiation therapy-induced erectile dysfunction. J Sex Med 9, 1834-1841.
    • (2012) J Sex Med , vol.9 , pp. 1834-1841
    • Qiu, X.1    Villalta, J.2    Ferretti, L.3    Fandel, T.M.4    Albersen, M.5    Lin, G.6
  • 32
    • 84863083395 scopus 로고    scopus 로고
    • Combined strategy of mesenchymal stem cell injection with vascular endothelial growth factor gene therapy for the treatment of diabetes-associated erectile dysfunction
    • Qiu X, Sun C, Yu W, Lin H, Sun Z, Chen Y et al. (2012b) Combined strategy of mesenchymal stem cell injection with vascular endothelial growth factor gene therapy for the treatment of diabetes-associated erectile dysfunction. J Androl 33, 37-44.
    • (2012) J Androl , vol.33 , pp. 37-44
    • Qiu, X.1    Sun, C.2    Yu, W.3    Lin, H.4    Sun, Z.5    Chen, Y.6
  • 33
    • 84860871817 scopus 로고    scopus 로고
    • Mobilisation of endothelial progenitor cells: one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats
    • Qiu XF, Li XX, Chen Y, Lin HC, Yu W, Wang R et al. (2012c) Mobilisation of endothelial progenitor cells: one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats. Asian J Androl 14, 481-486.
    • (2012) Asian J Androl , vol.14 , pp. 481-486
    • Qiu, X.F.1    Li, X.X.2    Chen, Y.3    Lin, H.C.4    Yu, W.5    Wang, R.6
  • 34
    • 0037300192 scopus 로고    scopus 로고
    • Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGFgene therapy prevent and reverse venogenic erectile dysfunction in rats
    • Rogers RS, Graziottin TM, Lin CS, Kan YW & Lue TF. (2003) Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGFgene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res 15, 26-37.
    • (2003) Int J Impot Res , vol.15 , pp. 26-37
    • Rogers, R.S.1    Graziottin, T.M.2    Lin, C.S.3    Kan, Y.W.4    Lue, T.F.5
  • 35
    • 34347397618 scopus 로고    scopus 로고
    • Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells
    • Song YS, Lee HJ, Park IH, Kim WK, Ku JH & Kim SU. (2007) Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells. Int J Impot Res 19, 378-385.
    • (2007) Int J Impot Res , vol.19 , pp. 378-385
    • Song, Y.S.1    Lee, H.J.2    Park, I.H.3    Kim, W.K.4    Ku, J.H.5    Kim, S.U.6
  • 36
    • 45449113410 scopus 로고    scopus 로고
    • Human neural crest stem cells transplanted in rat penile corpus cavernosum to repair erectile dysfunction
    • Song YS, Lee HJ, Park IH, Lim IS, Ku JH & Kim SU. (2008) Human neural crest stem cells transplanted in rat penile corpus cavernosum to repair erectile dysfunction. BJU Int 102, 220-224.
    • (2008) BJU Int , vol.102 , pp. 220-224
    • Song, Y.S.1    Lee, H.J.2    Park, I.H.3    Lim, I.S.4    Ku, J.H.5    Kim, S.U.6
  • 37
    • 67650661430 scopus 로고    scopus 로고
    • Transdifferentiation of rat fetal brain stem cells into penile smooth muscle cells
    • Song Y, Mehta N, Sheh B, Saljooque F & HS U, Rajasekaran M. (2009) Transdifferentiation of rat fetal brain stem cells into penile smooth muscle cells. BJU Int 104, 257-262.
    • (2009) BJU Int , vol.104 , pp. 257-262
    • Song, Y.1    Mehta, N.2    Sheh, B.3    Saljooque, F.4    HS, U.5    Rajasekaran, M.6
  • 39
    • 80053527692 scopus 로고    scopus 로고
    • Over-expression of VEGF165 in the adipose tissue-derived stem cells via the lentiviral vector
    • Sun XZ, Liu GH, Wang ZQ, Zheng FF, Bian J, Huang YP et al. (2011) Over-expression of VEGF165 in the adipose tissue-derived stem cells via the lentiviral vector. Chin Med J 124, 3093-3097.
    • (2011) Chin Med J , vol.124 , pp. 3093-3097
    • Sun, X.Z.1    Liu, G.H.2    Wang, Z.Q.3    Zheng, F.F.4    Bian, J.5    Huang, Y.P.6
  • 40
    • 84863870153 scopus 로고    scopus 로고
    • Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats
    • Sun C, Lin H, Yu W, Li X, Chen Y, Qiu X et al. (2012) Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats. Int J Androl 35, 601-607.
    • (2012) Int J Androl , vol.35 , pp. 601-607
    • Sun, C.1    Lin, H.2    Yu, W.3    Li, X.4    Chen, Y.5    Qiu, X.6
  • 41
    • 77955233814 scopus 로고    scopus 로고
    • Characterization of VEGF and angiopoietins expression in human corpus cavernosum during aging
    • Tomada N, Tomada I, Cruz F, Vendeira P & Neves D. (2010) Characterization of VEGF and angiopoietins expression in human corpus cavernosum during aging. J Sex Med 7, 1410-1418.
    • (2010) J Sex Med , vol.7 , pp. 1410-1418
    • Tomada, N.1    Tomada, I.2    Cruz, F.3    Vendeira, P.4    Neves, D.5
  • 42
    • 77950843974 scopus 로고    scopus 로고
    • Endothelial antioxidant administration ameliorates the erectile response to PDE5 regardless of the extension of the atherosclerotic process
    • Vicari E, La Vignera S, Condorelli R & Calogero AE. (2010) Endothelial antioxidant administration ameliorates the erectile response to PDE5 regardless of the extension of the atherosclerotic process. J Sex Med 7, 1247-1253.
    • (2010) J Sex Med , vol.7 , pp. 1247-1253
    • Vicari, E.1    La Vignera, S.2    Condorelli, R.3    Calogero, A.E.4
  • 43
    • 84865571698 scopus 로고    scopus 로고
    • Peripheral blood stem cells: phenotypic diversity and potential clinical applications
    • Zhang Y & Huang B. (2012) Peripheral blood stem cells: phenotypic diversity and potential clinical applications. Stem Cell Rev 8, 917-925.
    • (2012) Stem Cell Rev , vol.8 , pp. 917-925
    • Zhang, Y.1    Huang, B.2


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