cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.2023.5.n2257cardio-2257Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИRESEARCH ARTICLESST266 ингибирует процесс гиперплазии неоинтимы после баллонного повреждения артерии у крысST266 inhibits neointimal hyperplasia after arterial balloon injury in ratsЧенгСинь-МэнChengXin-Meng

PhD

Тайюань, Шаньси , Китай

PhD

Taiyuan, Shanxi 030032, China

chengxm0909@126.comЯнТаоYangTao

PhD

Тайюань, Шаньси , Китай

PhD

Taiyuan, Shanxi 030032, China

chengxm0909@126.comЦзыЯньZiYan

PhD

кафедра физиологии, Тайюань, Шаньси, Китай

PhD

Department of Physiology, Taiyuan, Shanxi, China

chengxm0909@126.comЧжанЛи-КуйZhangLi-Kui

MD，PhD

 Тайюань, Шаньси , Китай

MD，PhD

Taiyuan, Shanxi 030032, China

chengxm0909@126.comЯнЛин-БоYangLing-Bo

MD，PhD

Тайюань, Шаньси , Китай

MD，PhD

Taiyuan, Shanxi 030032, China

chengxm0909@126.comВанУильямWangWilliam

MD，PhD

отделение кардиохирургии, Ла-Хойя, Калифорния, США

MD，PhD

Department of Cardiac Surgery, La Jolla, CA, USA

chengxm0909@126.comВанСюэ-НинWangXue-Ning

MD，PhD

Тайюань, Шаньси , Китай

MD，PhD

Taiyuan, Shanxi 030032, China

chengxm0909@126.comТретья больница Медицинского университета Шаньси, Отделение сердечно-сосудистой хирургии, больница Шаньси Бетьюн, Академия медицинских наук Шаньси, больница Тунцзи ШаньсиКитайDivision of Cardiovascular Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi HospitalChinaМедицинский университет Шаньси, кафедра физиологииКитайShanxi Medical UniversityChinaМемориальная больница СкриппсаСоединённые Штаты АмерикиScripps Memorial HospitalUnited StatesТретья больница Медицинского университета Шаньси, Отделение сердечно-сосудистой хирургии , больница Шаньси Бетьюн, Академия медицинских наук Шаньси, больница Тунцзи ШаньсиКитайDivision of Cardiovascular Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi HospitalChina2023310520236355361Copyright © Kardiomag, 20232023KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/2257Цель

Цель. Изучить влияние мультипотентных клеток-предшественников (МКП) человеческого амниона и их нового секретома ST266 на гиперплазию неоинтимы после баллонного повреждения артерии у крыс.Материал и методы. Самцов крыс линии Спрег-Доули случайным образом разделили на четыре группы (n=7): контрольную группу, группу системного введения ST266, группу системного введения МКП и группу местной имплантации МКП. Гиперплазию неоинтимы индуцировали в подвздошной кости с помощью катетера для эмболэктомии 2F Fogarty. После операции крысам в группе ST266 вводили 0,1, 0,5 или 1 мл ST266 внутривенно ежедневно. В группе системного введения МКП однократная доза (SD) 0,5 × 106 или 1 × 106  клеток МКП вводилась через нижнюю полую вену после баллонного  повреждения артерии. В группе локальной имплантатации МКП 1×106, 5×106 или 20×106 клеток МКП имплантировали в 300 мкл Матригеля (Mtgl) вокруг подвздошной артерии после повреждения баллоном. Подвздошные артерии были удалены для гистологического анализа через 28 дней после операции. Индекс реэндотелизации измеряли через 10 дней после баллонного повреждения.Результаты. Группа ST266 (1 мл) имела более низкий уровень соотношения неоинтима/неоинтима+медиа (N/N+M) 0,3±0,1 против 0,5±0,1, p=0,004) и степень сужения просвета артерии (стеноз артерии - СА) (18,2±1,9)% против 39,2±5,8%, р=0,008) по сравнению с контрольной группой. Однократная доза МКП (1×106) снижала выраженность СА по сравнению с контрольной группой (19,5±5,4% против 39,2±5,8%, p=0,033). Значительное снижение N/N+M было обнаружено между имплантированными МКП (20 × 106) и контрольной группой (0,4 ± 0,1 против 0,5 ± 0,1, p = 0,003) и группой, получавшей только Матригель (0,5 ± 0,1, p = 0,007).  Имплантированные МКП (20 × 106) снижали СА по сравнению как с контролем (39,2 ± 5,8%, p = 0,001), так и с группой, получавшей только Матригель (37,5 ± 8,6%, p = 0,016). ST266 (1 мл) статистически значимо увеличивал индекс повторной эндотелизации по сравнению с контролем (0,4±0,1 против 0,1±0,1, р=0,002).Заключение. ST266 и МКП снижают образование неоинтимы и увеличивают индекс реэндотелизации после баллонного повреждения артерии. ST266 потенциально является новым терапевтическим средством для предотвращения рестеноза сосудов у человека.

 

 

Objective    To examine the effect of Human Amnion-Derived Multipotent Progenitor (AMP) cells and their novel ST266 secretome on neointimal hyperplasia after arterial balloon injury in rats.Material and Methods    Sprague-Dawley male rats were randomly divided into four groups (n=7): Control (PBS) group, systemic ST266 group, systemic AMP group and local AMP implant group. Neointimal hyperplasia was induced in the iliac using a 2F Fogarty embolectomy catheter. After surgery, the rats in the ST266 group were treated with 0.1, 0.5, or 1ml ST266 iv daily. In the systemic AMP groups, a single dose (SD) of 0.5 ×106 or 1×106 AMP cells was injected via the inferior vena cava after arterial balloon injury. In local AMP implant groups, 1×106, 5×106, or 20×106 AMP cells were implanted in 300 µl Matrigel (Mtgl) around the iliac artery after balloon injury. The iliac arteries were removed for histologic analysis at 28 days after the surgery. Re-endothelialization index was measured at 10 days after balloon injury.Results    ST266 (1 ml) group had a lower level of the Neointima / Neointima+Media ratio (N / N+M) 0.3±0.1 vs 0.5±0.1, p=0.004) and luminal stenosis (LS) percentage (18.2±1.9 % vs 39.2±5.8 %, p=0.008) compared with the control group. Single-dose AMP (1×106) decreased LS compared to the control group (19.5±5.4 % vs 39.2±5.8 %, p=0.033). Significant reduction in N / N+M were found between implanted AMPs (20×106) and the control group (0.4±0.1 vs 0.5±0.1, p=0.003) and the Mtgl-only group (0.5±0.1, p=0.007). Implanted AMPs (20×106) decreased the LS compared with both the control (39.2±5.8 %, p=0.001) and Mtgl-only group (37.5±8.6 %, p=0.016). ST266 (1 ml) significantly increased the re-endothelialization index compared to the control (0.4±0.1 vs 0.1±0.1, p=0.002).Conclusion    ST266 and AMP cells reduce neointimal formation and increase the re-endothelialization index after arterial balloon injury. ST266 is potentially a novel, therapeutic agent to prevent vascular restenosis in human.

 

Рестенознеоинтимабаллонная ангиопластикамультипотентный амнионклетки-предшественникиRestenosisneointimaballoon angioplastyamnion-derived multipotentprogenitor cellsResearch Project Supported by Shanxi Scholarship Council of China (grant number 2017-125) and by the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province (grant number 2016-07).No conflict of interest is reported.ReferencesGarg S, Serruys PW. Coronary Stents. Journal of the American College of Cardiology. 2010;56(10 Suppl):S1–42. DOI: 10.1016/j.jacc.2010.06.007Garg S, Serruys PW. Coronary Stents. Journal of the American College of Cardiology. 2010;56(10 Suppl):S1–42. DOI: 10.1016/j.jacc.2010.06.007Tanaka H, Sukhova GK, Swanson SJ, Clinton SK, Ganz P, Cybulsky MI et al. Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury. Circulation. 1993;88(4):1788–803. DOI: 10.1161/01.CIR.88.4.1788Tanaka H, Sukhova GK, Swanson SJ, Clinton SK, Ganz P, Cybulsky MI et al. Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury. Circulation. 1993;88(4):1788–803. DOI: 10.1161/01.CIR.88.4.1788Banas RA, Trumpower C, Bentlejewski C, Marshall V, Sing G, Zeevi A. Immunogenicity and immunomodulatory effects of amnion-derived multipotent progenitor cells. Human Immunology. 2008;69(6):321–8. DOI: 10.1016/j.humimm.2008.04.007Banas RA, Trumpower C, Bentlejewski C, Marshall V, Sing G, Zeevi A. Immunogenicity and immunomodulatory effects of amnion-derived multipotent progenitor cells. Human Immunology. 2008;69(6):321–8. DOI: 10.1016/j.humimm.2008.04.007Baker R, Urso-Baiarda F, Linge C, Grobbelaar A. Cutaneous scarring: a clinical review. Dermatology Research and Practice. 2009;2009:625376. DOI: 10.1155/2009/625376Baker R, Urso-Baiarda F, Linge C, Grobbelaar A. Cutaneous scarring: a clinical review. Dermatology Research and Practice. 2009;2009:625376. DOI: 10.1155/2009/625376Philip J, Hackl F, Canseco JA, Kamel RA, Kiwanuka E, Diaz-Siso JR et al. Amnion-derived multipotent progenitor cells improve achilles tendon repair in rats. Eplasty. 2013;13:e31. PMID: 23814634Philip J, Hackl F, Canseco JA, Kamel RA, Kiwanuka E, Diaz-Siso JR et al. Amnion-derived multipotent progenitor cells improve achilles tendon repair in rats. Eplasty. 2013;13:e31. PMID: 23814634Steed DL, Trumpower C, Duffy D, Smith C, Marshall V, Rupp R et al. Amnion-derived cellular cytokine solution: a physiological combination of cytokines for wound healing. Eplasty. 2008;8:e18. PMID: 18461121Steed DL, Trumpower C, Duffy D, Smith C, Marshall V, Rupp R et al. Amnion-derived cellular cytokine solution: a physiological combination of cytokines for wound healing. Eplasty. 2008;8:e18. PMID: 18461121Franz MG, Payne WG, Xing L, Naidu DK, Salas RE, Marshall VS et al. The use of amnion-derived cellular cytokine solution to improve healing in acute and chronic wound models. Eplasty. 2008;8:e21. PMID: 18470282Franz MG, Payne WG, Xing L, Naidu DK, Salas RE, Marshall VS et al. The use of amnion-derived cellular cytokine solution to improve healing in acute and chronic wound models. Eplasty. 2008;8:e21. PMID: 18470282Uberti MG, Lufkin AE, Pierpont YN, Ko F, Smith CA, Robson MC et al. Amnion–Derived Cellular Cytokine Solution Promotes Macrophage Activity. Annals of Plastic Surgery. 2011;66(5):575–80. DOI: 10.1097/SAP.0b013e318212f1d0Uberti MG, Lufkin AE, Pierpont YN, Ko F, Smith CA, Robson MC et al. Amnion–Derived Cellular Cytokine Solution Promotes Macrophage Activity. Annals of Plastic Surgery. 2011;66(5):575–80. DOI: 10.1097/SAP.0b013e318212f1d0Deng-Bryant Y, Readnower RD, Leung LY, Cunningham TL, Shear DA, Tortella FC. Treatment with amnion-derived cellular cytokine solution (ACCS) induces persistent motor improvement and ameliorates neuroinflammation in a rat model of penetrating ballistic-like brain injury. Restorative Neurology and Neuroscience. 2015;33(2):189–203. DOI: 10.3233/RNN-140455Deng-Bryant Y, Readnower RD, Leung LY, Cunningham TL, Shear DA, Tortella FC. Treatment with amnion-derived cellular cytokine solution (ACCS) induces persistent motor improvement and ameliorates neuroinflammation in a rat model of penetrating ballistic-like brain injury. Restorative Neurology and Neuroscience. 2015;33(2):189–203. DOI: 10.3233/RNN-140455Deng-Bryant Y, Chen Z, van der Merwe C, Liao Z, Dave JR, Rupp R et al. Long-term administration of amnion-derived cellular cytokine suspension promotes functional recovery in a model of penetrating ballistic-like brain injury. Journal of Trauma and Acute Care Surgery. 2012;73(2 Suppl 1):S156–64. DOI: 10.1097/TA.0b013e3182625f5fDeng-Bryant Y, Chen Z, van der Merwe C, Liao Z, Dave JR, Rupp R et al. Long-term administration of amnion-derived cellular cytokine suspension promotes functional recovery in a model of penetrating ballistic-like brain injury. Journal of Trauma and Acute Care Surgery. 2012;73(2 Suppl 1):S156–64. DOI: 10.1097/TA.0b013e3182625f5fVazquez-Padron RI, Mateu D, Rodriguez-Menocal L, Wei Y, Webster KA, Pham SM. Novel role of Egr-1 in nicotine-related neointimal formation. Cardiovascular Research. 2010;88(2):296–303. DOI: 10.1093/cvr/cvq213Vazquez-Padron RI, Mateu D, Rodriguez-Menocal L, Wei Y, Webster KA, Pham SM. Novel role of Egr-1 in nicotine-related neointimal formation. Cardiovascular Research. 2010;88(2):296–303. DOI: 10.1093/cvr/cvq213Niu C, Wang X, Zhao M, Cai T, Liu P, Li J et al. Macrophage Foam Cell–Derived Extracellular Vesicles Promote Vascular Smooth Muscle Cell Migration and Adhesion. Journal of the American Heart Association. 2016;5(10):e004099. DOI: 10.1161/JAHA.116.004099Niu C, Wang X, Zhao M, Cai T, Liu P, Li J et al. Macrophage Foam Cell–Derived Extracellular Vesicles Promote Vascular Smooth Muscle Cell Migration and Adhesion. Journal of the American Heart Association. 2016;5(10):e004099. DOI: 10.1161/JAHA.116.004099Li L, Zhang H-N, Chen H-Z, Gao P, Zhu L-H, Li H-L et al. SIRT1 Acts as a Modulator of Neointima Formation Following Vascular Injury in Mice. Circulation Research. 2011;108(10):1180–9. DOI: 10.1161/CIRCRESAHA.110.237875Li L, Zhang H-N, Chen H-Z, Gao P, Zhu L-H, Li H-L et al. SIRT1 Acts as a Modulator of Neointima Formation Following Vascular Injury in Mice. Circulation Research. 2011;108(10):1180–9. DOI: 10.1161/CIRCRESAHA.110.237875Khan RS, Dine K, Bauman B, Lorentsen M, Lin L, Brown H et al. Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model. Scientific Reports. 2017;7(1):41768. DOI: 10.1038/srep41768Khan RS, Dine K, Bauman B, Lorentsen M, Lin L, Brown H et al. Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model. Scientific Reports. 2017;7(1):41768. DOI: 10.1038/srep41768Forte A, Rinaldi B, Sodano L, Berrino L, Rossi F, Finicelli M et al. Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells. Cardiovascular Drugs and Therapy. 2012;26(1):9–21. DOI: 10.1007/s10557-011-6359-8Forte A, Rinaldi B, Sodano L, Berrino L, Rossi F, Finicelli M et al. Stem Cell Therapy for Arterial Restenosis: Potential Parameters Contributing to the Success of Bone Marrow-Derived Mesenchymal Stromal Cells. Cardiovascular Drugs and Therapy. 2012;26(1):9–21. DOI: 10.1007/s10557-011-6359-8Payne WG, Wachtel TL, Smith CA, Uberti MG, Ko F, Robson MC. Effect of Amnion-Derived Cellular Cytokine Solution on Healing of Experimental Partial-Thickness Burns. World Journal of Surgery. 2010;34(7):1663–8. DOI: 10.1007/s00268-010-0420-9Payne WG, Wachtel TL, Smith CA, Uberti MG, Ko F, Robson MC. Effect of Amnion-Derived Cellular Cytokine Solution on Healing of Experimental Partial-Thickness Burns. World Journal of Surgery. 2010;34(7):1663–8. DOI: 10.1007/s00268-010-0420-9Swanson N, Hogrefe K, Javed Q, Malik N, Gershlick AH. Vascular endothelial growth factor (VEGF)-eluting stents: in vivo effects on thrombosis, endothelialization and intimal hyperplasia. The Journal of Invasive Cardiology. 2003;15(12):688–92. PMID: 14660819Swanson N, Hogrefe K, Javed Q, Malik N, Gershlick AH. Vascular endothelial growth factor (VEGF)-eluting stents: in vivo effects on thrombosis, endothelialization and intimal hyperplasia. The Journal of Invasive Cardiology. 2003;15(12):688–92. PMID: 14660819Tang C, Wang G, Wu X, Li Z, Shen Y, Lee JC-M et al. The impact of vascular endothelial growth factor-transfected human endothelial cells on endothelialization and restenosis of stainless steel stents. Journal of Vascular Surgery. 2011;53(2):461–71. DOI: 10.1016/j.jvs.2010.08.020Tang C, Wang G, Wu X, Li Z, Shen Y, Lee JC-M et al. The impact of vascular endothelial growth factor-transfected human endothelial cells on endothelialization and restenosis of stainless steel stents. Journal of Vascular Surgery. 2011;53(2):461–71. DOI: 10.1016/j.jvs.2010.08.020Lijnen HR, Soloway P, Collen D. Tissue Inhibitor of Matrix Metalloproteinases-1 Impairs Arterial Neointima Formation After Vascular Injury in Mice. Circulation Research. 1999;85(12):1186–91. DOI: 10.1161/01.RES.85.12.1186Lijnen HR, Soloway P, Collen D. Tissue Inhibitor of Matrix Metalloproteinases-1 Impairs Arterial Neointima Formation After Vascular Injury in Mice. Circulation Research. 1999;85(12):1186–91. DOI: 10.1161/01.RES.85.12.1186Cho A, Reidy MA. Matrix Metalloproteinase-9 Is Necessary for the Regulation of Smooth Muscle Cell Replication and Migration After Arterial Injury. Circulation Research. 2002;91(9):845–51. DOI: 10.1161/01.RES.0000040420.17366.2ECho A, Reidy MA. Matrix Metalloproteinase-9 Is Necessary for the Regulation of Smooth Muscle Cell Replication and Migration After Arterial Injury. Circulation Research. 2002;91(9):845–51. DOI: 10.1161/01.RES.0000040420.17366.2EHatzi E, Badet J. Expression of receptors for human angiogenin in vascular smooth muscle cells. European Journal of Biochemistry. 1999;260(3):825–32. DOI: 10.1046/j.1432-1327.1999.00222.xHatzi E, Badet J. Expression of receptors for human angiogenin in vascular smooth muscle cells. European Journal of Biochemistry. 1999;260(3):825–32. DOI: 10.1046/j.1432-1327.1999.00222.xOrlidge A, D’Amore PA. Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. The Journal of Cell Biology. 1987;105(3):1455–62. DOI: 10.1083/jcb.105.3.1455Orlidge A, D’Amore PA. Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. The Journal of Cell Biology. 1987;105(3):1455–62. DOI: 10.1083/jcb.105.3.1455Dodge AB, Lu X, D’Amore PA. Density-dependent endothelial cell production of an inhibitor of smooth muscle cell growth. Journal of Cellular Biochemistry. 1993;53(1):21–31. DOI: 10.1002/jcb.240530104Dodge AB, Lu X, D’Amore PA. Density-dependent endothelial cell production of an inhibitor of smooth muscle cell growth. Journal of Cellular Biochemistry. 1993;53(1):21–31. DOI: 10.1002/jcb.240530104Feige JN, Auwerx J. Transcriptional targets of sirtuins in the coordination of mammalian physiology. Current Opinion in Cell Biology. 2008;20(3):303–9. DOI: 10.1016/j.ceb.2008.03.012Feige JN, Auwerx J. Transcriptional targets of sirtuins in the coordination of mammalian physiology. Current Opinion in Cell Biology. 2008;20(3):303–9. DOI: 10.1016/j.ceb.2008.03.012Zhang Q -j., Wang Z, Chen H -z., Zhou S, Zheng W, Liu G et al. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovascular Research. 2008;80(2):191–9. DOI: 10.1093/cvr/cvn224Zhang Q -j., Wang Z, Chen H -z., Zhou S, Zheng W, Liu G et al. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovascular Research. 2008;80(2):191–9. DOI: 10.1093/cvr/cvn224Welt FG, Tso C, Edelman ER, Kjelsberg MA, Paolini JF, Seifert P et al. Leukocyte recruitment and expression of chemokines following different forms of vascular injury. Vascular Medicine. 2003;8(1):1–7. DOI: 10.1191/1358863x03vm462oaWelt FG, Tso C, Edelman ER, Kjelsberg MA, Paolini JF, Seifert P et al. Leukocyte recruitment and expression of chemokines following different forms of vascular injury. Vascular Medicine. 2003;8(1):1–7. DOI: 10.1191/1358863x03vm462oaDanenberg HD, Welt FGP, Walker M, Seifert P, Toegel GS, Edelman ER. Systemic Inflammation Induced by Lipopolysaccharide Increases Neointimal Formation After Balloon and Stent Injury in Rabbits. Circulation. 2002;105(24):2917–22. DOI: 10.1161/01.CIR.0000018168.15904.BBDanenberg HD, Welt FGP, Walker M, Seifert P, Toegel GS, Edelman ER. Systemic Inflammation Induced by Lipopolysaccharide Increases Neointimal Formation After Balloon and Stent Injury in Rabbits. Circulation. 2002;105(24):2917–22. DOI: 10.1161/01.CIR.0000018168.15904.BBMaiguel D, Faridi MH, Wei C, Kuwano Y, Balla KM, Hernandez D et al. Small Molecule–Mediated Activation of the Integrin CD11b/CD18 Reduces Inflammatory Disease. Science Signaling. 2011;4(189):ra57. DOI: 10.1126/scisignal.2001811Maiguel D, Faridi MH, Wei C, Kuwano Y, Balla KM, Hernandez D et al. Small Molecule–Mediated Activation of the Integrin CD11b/CD18 Reduces Inflammatory Disease. Science Signaling. 2011;4(189):ra57. DOI: 10.1126/scisignal.2001811Banas R, Miller C, Guzik L, Zeevi A. Amnion-Derived Multipotent Progenitor Cells Inhibit Blood Monocyte Differentiation into Mature Dendritic Cells. Cell Transplantation. 2014;23(9):1111–25. DOI: 10.3727/096368913X670165Banas R, Miller C, Guzik L, Zeevi A. Amnion-Derived Multipotent Progenitor Cells Inhibit Blood Monocyte Differentiation into Mature Dendritic Cells. Cell Transplantation. 2014;23(9):1111–25. DOI: 10.3727/096368913X670165Rey FE, Pagano PJ. The Reactive Adventitia: Fibroblast Oxidase in Vascular Function. Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22(12):1962–71. DOI: 10.1161/01.ATV.0000043452.30772.18Rey FE, Pagano PJ. The Reactive Adventitia: Fibroblast Oxidase in Vascular Function. Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22(12):1962–71. DOI: 10.1161/01.ATV.0000043452.30772.18Conte MS, Nugent HM, Gaccione P, Roy-Chaudhury P, Lawson JH. Influence of diabetes and perivascular allogeneic endothelial cell implants on arteriovenous fistula remodeling. Journal of Vascular Surgery. 2011;54(5):1383–9. DOI: 10.1016/j.jvs.2011.05.005Conte MS, Nugent HM, Gaccione P, Roy-Chaudhury P, Lawson JH. Influence of diabetes and perivascular allogeneic endothelial cell implants on arteriovenous fistula remodeling. Journal of Vascular Surgery. 2011;54(5):1383–9. DOI: 10.1016/j.jvs.2011.05.005Nugent HM, Ng Y-S, White D, Groothius A, Kanner G, Edelman ER. Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model. Journal of Vascular Surgery. 2012;56(4):1078–88. DOI: 10.1016/j.jvs.2012.03.002Nugent HM, Ng Y-S, White D, Groothius A, Kanner G, Edelman ER. Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model. Journal of Vascular Surgery. 2012;56(4):1078–88. DOI: 10.1016/j.jvs.2012.03.002Hughes D, Fu AA, Puggioni A, Glockner JF, Anwer B, McGuire AM et al. Adventitial transplantation of blood outgrowth endothelial cells in porcine haemodialysis grafts alleviates hypoxia and decreases neointimal proliferation through a matrix metalloproteinase-9-mediated pathway--a pilot study. Nephrology Dialysis Transplantation. 2008;24(1):85–96. DOI: 10.1093/ndt/gfn433Hughes D, Fu AA, Puggioni A, Glockner JF, Anwer B, McGuire AM et al. Adventitial transplantation of blood outgrowth endothelial cells in porcine haemodialysis grafts alleviates hypoxia and decreases neointimal proliferation through a matrix metalloproteinase-9-mediated pathway--a pilot study. Nephrology Dialysis Transplantation. 2008;24(1):85–96. DOI: 10.1093/ndt/gfn433

The authors declare that there are no conflicts of interest present.