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Current Stem Cell Research & Therapy


ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Harnessing Stem Cell Potential for the Treatment of Erectile Function in Men with Diabetes Mellitus: From Preclinical/Clinical Perspectives to Penile Tissue Engineering

Author(s): Serap Gur and Wayne J.G. Hellstrom*

Volume 15 , Issue 4 , 2020

Page: [308 - 320] Pages: 13

DOI: 10.2174/1574888X14666190828142045

Price: $65


Background: According to the World Health Organization, more than 150 million people are diabetic, and this number will increase twofold by the year 2025. Diabetes-related complications affect all body organ systems, including the penis. Diabetes-induced Erectile Dysfunction (ED) is caused by neuropathy of the penile nerves and vasculopathy involving the smooth muscle and endothelium of the corpus cavernosum.

Objective: This study aims to present an overview of Stem Cell (SC) research in diabetic animal models of ED, focusing on the function, signaling, and niches that have a prominent role in the regeneration of cavernosal cells and penile tissues. We highlight common erectile pathologies caused by diabetes and review relevant preclinical trials. We also discuss paracrine mechanisms of various SC therapies involved in the repair of endothelial cells and cavernous nerves in these diabetic models.

Methods: A PubMed search was performed, with dates ranging from inception until Mar 31, 2019.

Results: This review provides a comprehensive evaluation of the various strategies that have been investigated for improving SC delivery methods, through preclinical literature and published clinical trials regarding ED in men with diabetes. Various cell-type applications have benefited erectile function in diabetic models of ED.

Conclusion: This review examines the progress and remaining challenges in diabetes-related SC research regarding ED. Moving forward, it is only with a combined effort of basic biology and translational work that the potential of SC-based therapies in diabetes in ED can be realized.

Keywords: Stem cell, diabetes mellitus, preclinical, erectile dysfunction, clinical trials, tissue engineering.

Cheng SK, Park EY, Pehar A, Rooney AC, Gallicano GI. Current progress of human trials using stem cell therapy as a treatment for diabetes mellitus. Am J Stem Cells 2016; 5(3): 74-86.
[PMID: 27853629]
Habtemariam S, Lentini G. The therapeutic potential of rutin for diabetes: an update. Mini Rev Med Chem 2015; 15(7): 524-8.
[] [PMID: 25934979]
Giuliano FA, Leriche A, Jaudinot EO, de Gendre AS. Prevalence of erectile dysfunction among 7689 patients with diabetes or hypertension, or both. Urology 2004; 64(6): 1196-201.
[] [PMID: 15596196]
De Berardis G, Franciosi M, Belfiglio M, et al. Quality of Care and Outcomes in Type 2 Diabetes (QuED) Study Group. Erectile dysfunction and quality of life in type 2 diabetic patients: a serious problem too often overlooked. Diabetes Care 2002; 25(2): 284-91.
[] [PMID: 11815497]
Cho NH, Ahn CW, Park JY, et al. Prevalence of erectile dysfunction in Korean men with Type 2 diabetes mellitus. Diabet Med 2006; 23(2): 198-203.
[] [PMID: 16433719]
Teles AG, Carreira M, Alarcão V, et al. Prevalence, severity, and risk factors for erectile dysfunction in a representative sample of 3,548 portuguese men aged 40 to 69 years attending primary healthcare centers: results of the Portuguese erectile dysfunction study. J Sex Med 2008; 5(6): 1317-24.
[] [PMID: 18194181]
Yang G, Pan C, Lu J. Prevalence of erectile dysfunction among Chinese men with type 2 diabetes mellitus. Int J Impot Res 2010; 22(5): 310-7.
[] [PMID: 20811390]
Malavige LS, Levy JC. Erectile dysfunction in diabetes mellitus. J Sex Med 2009; 6(5): 1232-47.
[] [PMID: 19210706]
Moore CR, Wang R. Pathophysiology and treatment of diabetic erectile dysfunction. Asian J Androl 2006; 8(6): 675-84.
[] [PMID: 16892168]
Hatzimouratidis K, Hatzichristou D. How to treat erectile dysfunction in men with diabetes: from pathophysiology to treatment. Curr Diab Rep 2014; 14(11): 545.
[] [PMID: 25193347]
Maiorino MI, Bellastella G, Esposito K. Diabetes and sexual dysfunction: current perspectives. Diabetes Metab Syndr Obes 2014; 7: 95-105.
[PMID: 24623985]
Zhou F, Hui Y, Xu Y, et al. Effects of adipose-derived stem cells plus insulin on erectile function in streptozotocin-induced diabetic rats. Int Urol Nephrol 2016; 48(5): 657-69.
[] [PMID: 26820518]
Wang L, Xu Y, Li H, et al. Antioxidant icariside II combined with insulin restores erectile function in streptozotocin-induced type 1 diabetic rats. J Cell Mol Med 2015; 19(5): 960-9.
[] [PMID: 25781208]
Wang L, Tian W, Uwais Z, et al. AGE-breaker ALT-711 plus insulin could restore erectile function in streptozocin-induced type 1 diabetic rats. J Sex Med 2014; 11(6): 1452-62.
[] [PMID: 24766706]
Usta MF, Kendirci M, Gur S, et al. The breakdown of preformed advanced glycation end products reverses erectile dysfunction in streptozotocin-induced diabetic rats: preventive versus curative treatment. J Sex Med 2006; 3(2): 242-50.
[] [PMID: 16490017]
Usta MF, Bivalacqua TJ, Koksal IT, Toptas B, Surmen S, Hellstrom WJ. The protective effect of aminoguanidine on erectile function in diabetic rats is not related to the timing of treatment. BJU Int 2004; 94(3): 429-32.
[] [PMID: 15291881]
Redrow GP, Thompson CM, Wang R. Treatment strategies for diabetic patients suffering from erectile dysfunction: an update. Expert Opin Pharmacother 2014; 15(13): 1827-36.
[] [PMID: 24976035]
Dorsey P, Keel C, Klavens M, Hellstrom WJ. Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of erectile dysfunction. Expert Opin Pharmacother 2010; 11(7): 1109-22.
[] [PMID: 20402554]
Yang J, Wang T, Zhang Y, Zhuan L, Xu H, Wang SG, et al. Inhibition of phosphodiesterase-5 improves therapeutic efficacy Of adipose-derived stem cells for erectile dysfunction in diabetic rats. J Urol 2014; 191(4): E481
Lin CS, Xin ZC, Wang Z, et al. Stem cell therapy for erectile dysfunction: a critical review. Stem Cells Dev 2012; 21(3): 343-51.
[] [PMID: 21793654]
Condorelli RA, Calogero AE, Vicari E, et al. Vascular regenerative therapies for the treatment of erectile dysfunction: current approaches. Andrology 2013; 1(4): 533-40.
[] [PMID: 23658196]
Yohannes E, Chang J, Tar MT, Davies KP, Chance MR. Molecular targets for diabetes mellitus-associated erectile dysfunction. Mol Cell Proteomics 2010; 9(3): 565-78.
[] [PMID: 20007950]
Gur S, Abdel-Mageed AB, Sikka SC, Hellstrom WJG. Advances in stem cell therapy for erectile dysfunction. Expert Opin Biol Ther 2018; 18(11): 1137-50.
[] [PMID: 30301368]
Piperi C, Goumenos A, Adamopoulos C, Papavassiliou AG. AGE/RAGE signalling regulation by miRNAs: associations with diabetic complications and therapeutic potential. Int J Biochem Cell Biol 2015; 60: 197-201.
[] [PMID: 25603271]
Alwaal A, Zaid UB, Lin CS, Lue TF. Stem cell treatment of erectile dysfunction. Adv Drug Deliv Rev 2015; 82-83: 137-44.
[] [PMID: 25446142]
Albersen M, Shindel AW, Mwamukonda KB, Lue TF. The future is today: emerging drugs for the treatment of erectile dysfunction. Expert Opin Emerg Drugs 2010; 15(3): 467-80.
[] [PMID: 20415601]
Albersen M, Lin G, Fandel TM, et al. Zhang H, Qiu X, Lin CS. Functional, metabolic, and morphologic characteristics of a novel rat model of type 2 diabetes-associated erectile dysfunction. Urology 2011; 78(2): e1-8.
Burke JP, Jacobson DJ, McGree ME, et al. Diabetes and sexual dysfunction: results from the Olmsted County study of urinary symptoms and health status among men. J Urol 2007; 177(4): 1438-42.
[] [PMID: 17382749]
Gur S, Kadowitz PJ, Hellstrom WJ. A critical appraisal of erectile function in animal models of diabetes mellitus. Int J Androl 2009; 32(2): 93-114.
[] [PMID: 19076258]
Bak E, Marcisz C, Krzeminska S, Dobrzyn-Matusiak D, Foltyn A, Drosdzol-Cop A. Does Type 1 Diabetes Modify Sexuality and Mood of Women and Men? Int J Environ Res Public Health 2018; 15(5): E958
[] [PMID: 29751592]
Sáenz de Tejada I, Angulo J, Cellek S, et al. Pathophysiology of erectile dysfunction. J Sex Med 2005; 2(1): 26-39.
[] [PMID: 16422902]
Tarhan F, Demirel GY, Kuyumcuoğlu U, Faydaci G, Eryildirim B. Apoptosis of corpus cavernosum in patients with organic erectile dysfunction. World J Urol 2009; 27(2): 235-40.
[] [PMID: 18846380]
Angulo J, González-Corrochano R, Cuevas P, et al. Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries. J Sex Med 2010; 7(2 Pt 1): 758-68.
[] [PMID: 19912487]
Tousoulis D, Tsarpalis K, Cokkinos D, Stefanadis C. Effects of insulin resistance on endothelial function: possible mechanisms and clinical implications. Diabetes Obes Metab 2008; 10(10): 834-42.
[] [PMID: 18034844]
Jansson PA. Endothelial dysfunction in insulin resistance and type 2 diabetes. J Intern Med 2007; 262(2): 173-83.
[] [PMID: 17645585]
Wu Z, Wang H, Ni F, et al. Islet transplantation improved penile tissue fibrosis in a rat model of type 1 diabetes. BMC Endocr Disord 2018; 18(1): 49.
[] [PMID: 30053902]
Algeffari M, Jayasena CN, MacKeith P, Thapar A, Dhillo WS, Oliver N. Testosterone therapy for sexual dysfunction in men with Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabet Med 2018; 35(2): 195-202.
[] [PMID: 29171080]
Li M, Li H, Ruan Y, Wang T, Liu J. Stem Cell Therapy for Diabetic Erectile Dysfunction in Rats: A Meta-Analysis. PLoS One 2016; 11(4): e0154341
[] [PMID: 27111659]
Bivalacqua TJ, Deng W, Kendirci M, et al. Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am J Physiol Heart Circ Physiol 2007; 292(3): H1278-90.
[] [PMID: 17071732]
Albersen M, Fandel TM, Lin G, et al. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med 2010; 7(10): 3331-40.
[] [PMID: 20561166]
Gokce A, Abd Elmageed ZY, Lasker GF, et al. Intratunical Injection of Genetically Modified Adipose Tissue-Derived Stem Cells with Human Interferon α-2b for Treatment of Erectile Dysfunction in a Rat Model of Tunica Albugineal Fibrosis. J Sex Med 2015; 12(7): 1533-44.
[] [PMID: 26062100]
Wu JH, Xia SJ. Stem cell-based therapy for erectile dysfunction. Chin Med J (Engl) 2011; 124(22): 3810-5.
[PMID: 22340246]
Liu J, Zhou F, Li GY, et al. Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats. Int J Mol Sci 2013; 14(5): 10661-73.
[] [PMID: 23698784]
Qiu X, Fandel TM, Ferretti L, et al. Both immediate and delayed intracavernous injection of autologous adipose-derived stromal vascular fraction enhances recovery of erectile function in a rat model of cavernous nerve injury. Eur Urol 2012; 62(4): 720-7.
[] [PMID: 22397847]
Musicki B, Burnett AL. Endothelial dysfunction in diabetic erectile dysfunction. Int J Impot Res 2007; 19(2): 129-38.
[] [PMID: 16775612]
Polymeri A, Giannobile WV, Kaigler D. Bone marrow stromal stem cells in tissue engineering and regenerative medicine. Horm Metab Res 2016; 48(11): 700-13.
[] [PMID: 27871114]
Dai R, Wang Z, Samanipour R, Koo KI, Kim K. Adipose-derived stem cells for tissue engineering and regenerative medicine applications. Stem Cells Int 2016; 2016: 6737345
[] [PMID: 27057174]
Kargozar S, Mozafari M, Hamzehlou S, Milan PB, Kim HW, Baino F. Bone tissue engineering using human cells: A comprehensive review on recent trends, current prospects, and recommendations. Appl Sci (Basel) 2019; 9(1)
Wu H, Mahato RI. Mesenchymal stem cell-based therapy for type 1 diabetes. Discov Med 2014; 17(93): 139-43.
[PMID: 24641956]
Lin CS, Xin ZC, Deng CH, Ning H, Lin G, Lue TF. Recent advances in andrology-related stem cell research. Asian J Androl 2008; 10(2): 171-5.
[] [PMID: 18286209]
Janeczek Portalska K, Leferink A, Groen N, et al. Endothelial differentiation of mesenchymal stromal cells. PLoS One 2012; 7(10): e46842
[] [PMID: 23056481]
Lee RH, Oh JY, Choi H, Bazhanov N. Therapeutic factors secreted by mesenchymal stromal cells and tissue repair. J Cell Biochem 2011; 112(11): 3073-8.
[] [PMID: 21748781]
Lalu MM, McIntyre L, Pugliese C, et al. Canadian Critical Care Trials Group. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One 2012; 7(10): e47559
[] [PMID: 23133515]
Long X, Tharp DL, Georger MA, et al. The smooth muscle cell-restricted KCNMB1 ion channel subunit is a direct transcriptional target of serum response factor and myocardin. J Biol Chem 2009; 284(48): 33671-82.
[] [PMID: 19801679]
He Y, He W, Qin G, Luo J, Xiao M. Transplantation KCNMA1 modified bone marrow-mesenchymal stem cell therapy for diabetes mellitus-induced erectile dysfunction. Andrologia 2014; 46(5): 479-86.
[] [PMID: 23646921]
Salkoff L, Butler A, Ferreira G, Santi C, Wei A. High-conductance potassium channels of the SLO family. Nat Rev Neurosci 2006; 7(12): 921-31.
[] [PMID: 17115074]
Bahk JY, Jung JH, Han H, Min SK, Lee YS. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant 2010; 8(2): 150-60.
[PMID: 20565373]
Qiu X, Lin H, Wang Y, et al. Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med 2011; 8(2): 427-36.
[] [PMID: 21091881]
Sun C, Lin H, Yu W, et al. Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats. Int J Androl 2012; 35(4): 601-7.
[] [PMID: 22428616]
Lei H, Liu J, Li H, et al. Low-intensity shock wave therapy and its application to erectile dysfunction. World J Mens Health 2013; 31(3): 208-14.
[] [PMID: 24459653]
Shan HT, Zhang HB, Chen WT, et al. Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats. Asian J Androl 2017; 19(1): 26-33.
[PMID: 27427555]
Zhu GQ, Jeon SH, Bae WJ, et al. Efficient promotion of autophagy and angiogenesis using mesenchymal stem cell therapy enhanced by the low-energy shock waves in the treatment of erectile dysfunction. Stem Cells Int 2018; 2018: 1302672
[] [PMID: 30228820]
Li Y, Pan E, Wang Y, Zhu X, Wei A. Flk-1+Sca-1− mesenchymal stem cells: functional characteristics in vitro and regenerative capacity in vivo. Int J Clin Exp Pathol 2015; 8(9): 9875-88.
[PMID: 26617697]
Ryu JK, Kim DH, Song KM, et al. Intracavernous delivery of clonal mesenchymal stem cells rescues erectile function in the streptozotocin-induced diabetic mouse. Andrology 2016; 4(1): 172-84.
[] [PMID: 26711324]
Chen F, Zhang H, Wang Z, et al. Adipose-derived stem cell-derived exosomes ameliorate erectile dysfunction in a rat model of type 2 diabetes. J Sex Med 2017; 14(9): 1084-94.
[] [PMID: 28781215]
Sun X, Luo LH, Feng L, Li DS. Down-regulation of lncRNA MEG3 promotes endothelial differentiation of bone marrow derived mesenchymal stem cells in repairing erectile dysfunction. Life Sci 2018; 208: 246-52.
[] [PMID: 30012476]
Qiu XF, Li XX, Chen Y, et al. 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 2012; 14(3): 481-6.
[] [PMID: 22367180]
Gou X, He WY, Xiao MZ, et al. Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats. Asian J Androl 2011; 13(2): 332-8.
[] [PMID: 21113173]
Sun K, Zhou Z, Ju X, et al. Combined transplantation of mesenchymal stem cells and endothelial progenitor cells for tissue engineering: a systematic review and meta-analysis. Stem Cell Res Ther 2016; 7(1): 151.
[] [PMID: 27724974]
Salem ESB, Fan GC. Pathological effects of exosomes in mediating diabetic cardiomyopathy. Adv Exp Med Biol 2017; 998: 113-38.
[] [PMID: 28936736]
Hassanpour M, Cheraghi O, Brazvan B, et al. Chronic exposure of human endothelial progenitor cells to diabetic condition abolished the regulated kinetics activity of exosomes. Iran J Pharm Res 2018; 17(3): 1068-80.
[PMID: 30127829]
Kim SM, Kim HS. Engineering of extracellular vesicles as drug delivery vehicles. Stem Cell Investig 2017; 4: 74.
[] [PMID: 29057246]
Conigliaro A, Fontana S, Raimondo S, Alessandro R. Exosomes: Nanocarriers of Biological Messages. Adv Exp Med Biol 2017; 998: 23-43.
[] [PMID: 28936730]
Altanerova U, Jakubechova J, Repiska V, Altaner C. Exosomes of human mesenchymal stem/stromal/medicinal signaling cells. Neoplasma 2017; 64(6): 809-15.
[] [PMID: 28895404]
Wang X, Liu C, Li S, et al. Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection. PLoS One 2015; 10(3): e0118951
[] [PMID: 25790284]
Liang L, Li Z, Ma T, et al. Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates Critical Limb Ischemia in Diabetic Nude Rats. Cell Transplant 2017; 26(1): 45-61.
[] [PMID: 27501782]
Wassef MAE, Tork OM, Rashed LA, Ibrahim W, Morsi H, Rabie DMM. Mitochondrial Dysfunction in Diabetic Cardiomyopathy: Effect of Mesenchymal Stem Cell with PPAR-γ Agonist or Exendin-4. Exp Clin Endocrinol Diabetes 2018; 126(1): 27-38.
[] [PMID: 28449155]
Jeon SH, Zhu GQ, Bae WJ, et al. Engineered Mesenchymal Stem Cells Expressing Stromal Cell-derived Factor-1 Improve Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats. Int J Mol Sci 2018; 19(12): E3730
[] [PMID: 30477146]
Al Demour S, Jafar H, Adwan S, et al. Safety and Potential Therapeutic Effect of Two Intracavernous Autologous Bone Marrow Derived Mesenchymal Stem Cells injections in Diabetic Patients with Erectile Dysfunction: An Open Label Phase I Clinical Trial. Urol Int 2018; 101(3): 358-65.
[] [PMID: 30173210]
Liu G, Sun X, Bian J, et al. Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model. PLoS One 2013; 8(8): e72790
[] [PMID: 24023647]
Nishimatsu H, Suzuki E, Kumano S, et al. Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration of erectile function in diabetic rats. J Sex Med 2012; 9(2): 482-93.
[] [PMID: 21951711]
Chen XD, Dusevich V, Feng JQ, Manolagas SC, Jilka RL. Extracellular matrix made by bone marrow cells facilitates expansion of marrow-derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts. J Bone Miner Res 2007; 22(12): 1943-56.
[] [PMID: 17680726]
Garcia MM, Fandel TM, Lin G, et al. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. J Sex Med 2010; 7(1 Pt 1): 89-98.
[] [PMID: 20104670]
Paek HJ, Kim C, Williams SK. Adipose stem cell-based regenerative medicine for reversal of diabetic hyperglycemia. World J Diabetes 2014; 5(3): 235-43.
[] [PMID: 24936245]
Das ND, Song KM, Yin GN, et al. Xenogenic transplantation of human breast adipose-derived stromal vascular fraction enhances recovery of erectile function in diabetic mice. Biol Reprod 2014; 90(3): 66.
[] [PMID: 24501171]
Skakun NP, Shman’ko VV. [Antioxidant effectiveness in isoniazid-induced lesions of the liver]. Farmakol Toksikol 1986; 49(4): 86-9.
[PMID: 3758339]
Qiu X, Sun C, Yu W, et al. Combined strategy of mesenchymal stem cell injection with vascular endothelial growth factor gene therapy for the treatment of diabetes-associated erectile dysfunction. J Androl 2012; 33(1): 37-44.
[] [PMID: 21311050]
Shen YH, Jiang HX, Qin SY, Wei LP, Meng YC, Luo W. [Activation of hepatocyte growth factor promotes apoptosis of hepatic stellate cells via the Rho pathway]. Zhonghua Gan Zang Bing Za Zhi. 2014; 22(2): 136-41. [Activation of hepatocyte growth factor promotes apoptosis of hepatic stellate cells via the Rho pathway].
[PMID: 24735597]
Yi SL, Liu XJ, Zhong JQ, Zhang Y. Role of caveolin-1 in atrial fibrillation as an anti-fibrotic signaling molecule in human atrial fibroblasts. PLoS One 2014; 9(1): e85144
[] [PMID: 24454806]
Liu T, Peng Y, Jia C, Fang X, Li J, Zhong W. Hepatocyte growth factor-modified adipose tissue-derived stem cells improve erectile function in streptozotocin-induced diabetic rats. Growth Factors 2015; 33(4): 282-9.
[] [PMID: 26339935]
Lu J, Xin Z, Zhang Q, et al. Beneficial effect of PEDF-transfected ADSCs on erectile dysfunction in a streptozotocin-diabetic rat model. Cell Tissue Res 2016; 366(3): 623-37.
[] [PMID: 27655233]
Kovanecz I, Vernet D, Masouminia M, et al. Implanted Muscle-Derived Stem Cells Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes, but Their Repair Capacity Is Impaired by Their Prior Exposure to the Diabetic Milieu. J Sex Med 2016; 13(5): 786-97.
[] [PMID: 27114192]
Zhu LL, Zhang Z, Jiang HS, Chen H, Chen Y, Dai YT. Superparamagnetic iron oxide nanoparticle targeting of adipose tissue-derived stem cells in diabetes-associated erectile dysfunction. Asian J Androl 2017; 19(4): 425-32.
[] [PMID: 27157506]
Seftel AD. Re: Combination of Mesenchymal Stem Cell Injection with Icariin for the Treatment of Diabetes-Associated Erectile Dysfunction. J Urol 2017; 198(2): 238.
[] [PMID: 29370619]
Zhu LL, Huang X, Yu W, Chen H, Chen Y, Dai YT. Transplantation of adipose tissue-derived stem cell-derived exosomes ameliorates erectile function in diabetic rats. Andrologia 2018; 50(2)
[] [PMID: 29057541]
Zhou F, Hui Y, Xin H, et al. Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats. Asian J Androl 2017; 19(1): 91-7.
[PMID: 27345005]
Castiglione F, Hedlund P, Weyne E, et al. Trauma and Reconstructive Urology Working Party of the European Association of Urology Young Academic Urologists. Intratunical Injection of Human Adipose Tissue-Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie’s Disease. Sex Med 2019; 7(1): 94-103.
[] [PMID: 30503767]
Veeraputhiran M, Ware J, Dent J. Bornhorst J, Post G, Cottler-Fox M, et al . A comparison of washed and volume-reduced platelets with respect to platelet activation, aggregation, and plasma protein removal. Transfusion 2011; 51(5): 1030-6.
Sanchez-Gonzalez DJ, Mendez-Bolaina E, Trejo-Bahena NI. Platelet-rich plasma peptides: key for regeneration. Int J Pept 2012; 2012: 532519
Reddi AS, Kuppasani K, Ende N. Human umbilical cord blood as an emerging stem cell therapy for diabetes mellitus. Curr Stem Cell Res Ther 2010; 5(4): 356-61.
[] [PMID: 20528762]
Cengiz T, Kaya E, Oral DY, et al. Intracavernous Injection of Human Umbilical Cord Blood Mononuclear Cells Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats. J Sex Med 2017; 14(1): 50-8.
[] [PMID: 28065360]
Nagaishi K, Mizue Y, Chikenji T, et al. Umbilical cord extracts improve diabetic abnormalities in bone marrow-derived mesenchymal stem cells and increase their therapeutic effects on diabetic nephropathy. Sci Rep 2017; 7(1): 8484.
[] [PMID: 28814814]
Falzarano MS, Ferlini A. Urinary Stem Cells as Tools to Study Genetic Disease: Overview of the Literature. J Clin Med 2019; 8(5): E627
[] [PMID: 31071994]
Guan J, Zhang J, Li H, et al. Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration. PLoS One 2015; 10(5): e0125253
[] [PMID: 25970295]
Pavathuparambil Abdul Manaph N, Al-Hawwas M, Bobrovskaya L, Coates PT, Zhou XF. Urine-derived cells for human cell therapy. Stem Cell Res Ther 2018; 9(1): 189.
[] [PMID: 29996911]
Zhang Y, Atala A. Urothelial cell culture: stratified urothelial sheet and three-dimensional growth of urothelial structure. Methods Mol Biol 2013; 945: 383-99.
[] [PMID: 23097119]
Ouyang B, Sun X, Han D, et al. Human urine-derived stem cells alone or genetically-modified with FGF2 Improve type 2 diabetic erectile dysfunction in a rat model. PLoS One 2014; 9(3): e92825
[] [PMID: 24663037]
Zhu Q, Li Q, Niu X, et al. Extracellular Vesicles Secreted by Human Urine-Derived Stem Cells Promote Ischemia Repair in a Mouse Model of Hind-Limb Ischemia. Cell Physiol Biochem 2018; 47(3): 1181-92.
[] [PMID: 30041250]
Jiang ZZ, Liu YM, Niu X, et al. Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats. Stem Cell Res Ther 2016; 7: 24.
[] [PMID: 26852014]
Masouminia M, Gelfand R, Kovanecz I, et al. Dyslipidemia Is a Major Factor in Stem Cell Damage Induced by Uncontrolled Long-Term Type 2 Diabetes and Obesity in the Rat, as Suggested by the Effects on Stem Cell Culture. J Sex Med 2018; 15(12): 1678-97.
[] [PMID: 30527052]
Omi M, Hata M, Nakamura N, et al. Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy. J Diabetes Investig 2016; 7(4): 485-96.
[] [PMID: 27181261]
Litwinoff E, Hurtado Del Pozo C, Ramasamy R, Schmidt AM. Emerging Targets for Therapeutic Development in Diabetes and Its Complications: The RAGE Signaling Pathway. Clin Pharmacol Ther 2015; 98(2): 135-44.
[] [PMID: 25974754]
Ramasamy R, Shekhtman A, Schmidt AM. The multiple faces of RAGE--opportunities for therapeutic intervention in aging and chronic disease. Expert Opin Ther Targets 2016; 20(4): 431-46.
[] [PMID: 26558318]
Howard AC, McNeil AK, Xiong F, Xiong WC, McNeil PL. A novel cellular defect in diabetes: membrane repair failure. Diabetes 2011; 60(11): 3034-43.
[] [PMID: 21940783]
Liu S, Chen F, Wang L, et al. 2,5-hexanedione induced apoptosis of rat bone marrow mesenchymal stem cells by reactive oxygen species. J Occup Health 2016; 58(2): 170-8.
[] [PMID: 27010086]
Lu YQ, Lu Y, Li HJ, Cheng XB. Effect of advanced glycosylation end products (AGEs) on proliferation of human bone marrow mesenchymal stem cells (MSCs) in vitro. In Vitro Cell Dev Biol Anim 2012; 48(9): 599-602.
[] [PMID: 23054442]
Hu J, Wang J. From embryonic stem cells to induced pluripotent stem cells-Ready for clinical therapy? Clin Transplant 2019; 33(6): e13573
[] [PMID: 31013374]
Bochinski D, Lin GT, Nunes L, et al. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int 2004; 94(6): 904-9.
[] [PMID: 15476533]
Zhang H, Albersen M, Jin X, Lin G. Stem cells: novel players in the treatment of erectile dysfunction. Asian J Androl 2012; 14(1): 145-55.
[] [PMID: 22002437]
Fansa H, Keilhoff G. [Factors influencing nerve regeneration]. Handchir Mikrochir Plast Chir 2003; 35(2): 72-82. [Factors influencing nerve regeneration].
[PMID: 12874718]
Sun Y, Jin K, Xie L, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 2003; 111(12): 1843-51.
[] [PMID: 12813020]
Stadtfeld M, Apostolou E, Akutsu H, et al. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 2010; 465(7295): 175-81.
[] [PMID: 20418860]
Liu L, Luo GZ, Yang W, et al. Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells. J Biol Chem 2010; 285(25): 19483-90.
[] [PMID: 20382743]
Ilic D, Devito L, Miere C, Codognotto S. Human embryonic and induced pluripotent stem cells in clinical trials. Br Med Bull 2015; 116: 19-27.
[] [PMID: 26582538]
Wespes E, Amar E, Hatzichristou D, Montorsi F, Pryor J, Vardi Y. European Association of Urology. Guidelines on erectile dysfunction. Eur Urol 2002; 41(1): 1-5.
[] [PMID: 11999460]
Stoltz JF, Bensoussan D, De Isla N, et al. Stem cells and vascular regenerative medicine: A mini review. Clin Hemorheol Microcirc 2016; 64(4): 613-33.
[] [PMID: 27791997]
Liu S, Zhang H, Zhang X, et al. Synergistic angiogenesis promoting effects of extracellular matrix scaffolds and adipose-derived stem cells during wound repair. Tissue Eng Part A 2011; 17(5-6): 725-39.
[] [PMID: 20929282]
Tobita M, Tajima S, Mizuno H. Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness. Stem Cell Res Ther 2015; 6: 215.
[] [PMID: 26541973]
Varma MJ, Breuls RG, Schouten TE, et al. Phenotypical and functional characterization of freshly isolated adipose tissue-derived stem cells. Stem Cells Dev 2007; 16(1): 91-104.
[] [PMID: 17348807]
Rombouts WJ, Ploemacher RE. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia 2003; 17(1): 160-70.
[] [PMID: 12529674]
Baer PC. Adipose-derived mesenchymal stromal/stem cells: An update on their phenotype in vivo and in vitro. World J Stem Cells 2014; 6(3): 256-65.
[] [PMID: 25126376]
Cramer C, Freisinger E, Jones RK, et al. Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Stem Cells Dev 2010; 19(12): 1875-84.
[] [PMID: 20380516]
El Osta R, Decot V, Bensoussan D, Stoltz JF, Eschwege P, Hubert J. [Treatment by stem cell therapy of erectile dysfunction of diabetic origin: State of the art]. Prog Urol 2018; 28(2): 74-84.
[] [PMID: 29170014]
Chung E. Stem cell therapy in diabetic men with erectile dysfunction: a step closer to safe and effective regenerative technology. Ann Transl Med 2019; 7(Suppl. 1): S40.
[] [PMID: 31032319]

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