Yu Mingming,Chen Fang.Research progress of tissue engineering in pediatric urology[J].Journal of Clinical Pediatric Surgery,2020,19(04):285-291.[doi:10.3969/j.issn.1671-6353.2020.04.001]
组织工程技术在儿童下尿路重建修复中的若干问题
- Title:
- Research progress of tissue engineering in pediatric urology
- Keywords:
- Tissue Engineering; Urinary Bladder; Urethra; Stem Cells Transplantion; Child
- 分类号:
- R726.9;R691.1
- 摘要:
- 组织工程的发展日新月异,并且在儿童下尿路重建修复的临床前研究中取得了不错的成效。但临床前研究在向临床转化时效果都不太理想。临床转化失败的原因很多,其中最重要的一点是临床前研究常使用的是健康动物模型,从而不能准确模拟病态组织的结构和功能。针对当前组织工程向临床转化的困境,很多新的研究方案也应运而生,包括使用多种来源的干细胞,改善移植物血供,应用可控释放生长因子的新型支架,探究深层次的信号通路以及细胞间相互作用等,但单用其中一种方法很难在临床应用中获得成功。本文阐述组织工程技术在儿童下尿路重建修复中已取得的研究进展及当前面临的主要问题。
- Abstract:
- Tissue engineering undergoes constant evolutions and it has achieved considerable progress in pediatric urology.However,almost all outcomes of clinical application have been unsatisfactory.Many reasons may explain a failure of clinical transformation and the most important one is that healthy animal models,employed frequently for preclinical studies,fail to accurately imitate the structures and functions of pathological tissues.For overcoming current difficulties of clinical transformation,many new research programs have emerged,including using stem cells from various sources,improving blood supply of grafts,employing new scaffolds with a controllable release of growth factors,exploring deep signaling pathways and cellular interactions.None of the methods alone can achieve final success in clinical practice.This paper reviews the progress and major dilemmas of tissue engineering in pediatric lower urinary tract and discusses their solutions.
参考文献/References:
1 Ross JPJ,Keays M,Neville C,et al.Pediatric bladder augmentation-Panacea or Pandora’s box?[J].Can Urol Assoc J,2020,14(6):1-13.DOI:10.5489/cuaj.6024.
2 Stein R,Zahn K,Huck N.Current indications and techniques for the use of bowel segments in pediatric urinary tract reconstruction[J].Front Pediatr,2019,7:236.DOI:10.3389/fped.2019.00236.eCollection2019.
3 贾幸,谢华.尿道下裂阴茎下弯的组织学和手术治疗研究进展[J].临床小儿外科杂志,2019,18(9):795-799,802.DOI:10.3969/j.issn.1671-6353.2019.09.018. Jia X,Xie H.Research advances in histology and surgery of ventral penile curvature in hypospadias[J].J Clin Ped Sur,2019,18(9):795-799,802.DOI:10.3969/j.issn.1671-6353.2019.09.018.
4 Versteegden LR,de Jonge PK,IntHout J,et al.Tissue engineering of the urethra:a systematic review and meta-analysis of preclinical and clinical studies[J].Eur Urol,2017,72(4):594-606.DOI:10.1016/j.eururo.2017.03.026.
5 Sharma S,Gupta DK.Tissue Engineering and Stem Cell Therapy in Pediatric Urology[J].J Indian Assoc Pediatr Surg,2019,24(4):237-246.DOI:10.4103/jiaps.JIAPS_77_18.
6 Wang F,Song Q,Du L,et al.Development and characterization of an acellular porcine small intestine submucosa scaffold for use in corneal epithelium tissue engineering[J].Curr Eye Res,2020,45(2):134-143.DOI:10.1080/02713683.2019.1663386.
7 Zhao F,Zhou L,Liu J,et al.Construction of a vascularized bladder with autologous adipose-derived stromal vascular fraction cells combined with bladder acellular matrix via tissue engineering[J].J Tissue Eng,2019,10:2041731419891256.DOI:10.1177/2041731419891256.
8 Nguyen TP,Nguyen QV,Nguyen VH,et al.Silk fibroin-based biomaterials for biomedical applications:a review[J].Polymers (Basel),2019,11(12):E1933.DOI:10.3390/polym11121933.
9 Versteegden LR,van Kampen KA,Janke HP,et al.Tubular collagen scaffolds with radial elasticity for hollow organ regeneration[J].Acta Biomater,2017,52:1-8.DOI:10.1016/j.actbio.2017.02.005.
10 Qiu YL,Chen X,Hou YL,et al.Characterization of different biodegradable scaffolds in tissue engineering[J].Mol Med Rep,2019,19(5):4043-4056.DOI:10.3892/mmr.2019.10066.
11 Xu ZC,Zhang Q,Li H.Elastic large muscular vessel wall engineered with bone marrow-derived cells under pulsatile stimulation in a bioreactor[J].Mol Med Rep,2015,12(4):6005-6012.DOI:10.3892/mmr.2015.4147.
12 Wang DJ,Li MY,Huang WT,et al.Repair of urethral defects with polylactid acid fibrous membrane seeded with adipose-derived stem cells in a rabbit model[J].Connect Tissue Res,2015,56(6):434-439.DOI:10.3109/03008207.2015.1035376.
13 Zhou Z,Yan H,Liu Y,et al.Adipose-derived stem-cell-implanted poly(ε-caprolactone)/chitosan scaffold improves bladder regeneration in a rat model[J].Regen Med,2018,13(3):331-342.DOI:10.2217/rme-2017-0120.
14 Tan HL,Kai D,Pasbakhsh P,et al.Electrospun cellulose acetate butyrate/polyethylene glycol (CAB/PEG) composite nanofibers:A potential scaffold for tissue engineering[J].Colloids Surf B Biointerfaces,2019,188:110713.DOI:10.1016/j.colsurfb.2019.110713.
15 Sánchez-Pech JC,Rosales-Ibá?es R,Cauich-Rodriguez JV,et al.Design,synthesis,characterization,and cytotoxicity of PCL/PLGA scaffolds through plasma treatment in the presence of pyrrole for possible use in urethral tissue engineering[J].J Biomater Appl,2020,34(6):840-850.DOI:10.1177/0885328219882638.
16 Culenova M,Ziaran S,Danisovic L.Cells involved in urethral tissue engineering:systematic review[J].Cell Transplant,2019,28(9-10):1106-1115.DOI:10.1177/0963689719854363.
17 Xia D,Yang Q,Fung KM,et al.Immunomodulatory response of layered small intestinal submucosa in a rat bladder regeneration model[J].J Biomed Mater Res B Appl Biomater,2019,107(6):1960-1969.DOI:10.1002/jbm.b.34289.
18 Wang C,Chen C,Guo M,et al.Stretchable collagen-coated polyurethane-urea hydrogel seeded with bladder smooth muscle cells for urethral defect repair in a rabbit model[J].J Mater Sci Mater Med,2019,30(12):135.DOI:10.1007/s10856-019-6342-7.
19 Lv X,Feng C,Liu Y,et al.A smart bilayered scaffold supporting keratinocytes and muscle cells in micro/nano-scale for urethral reconstruction[J].Theranostics,2018,8(11):3153-3163.DOI:10.7150/thno.22080.
20 Pokrywczynska M,Jundzill A,Rasmus M,et al.Understanding the role of mesenchymal stem cells in urinary bladder regeneration-a preclinical study on a porcine model[J].Stem Cell Res Ther,2018,9(1):328.DOI:10.1186/s13287-018-1070-3.
21 Atala A,Bauer SB,Soker S,et al.Tissue-engineered autologous bladders for patients needing cystoplasty[J].Lancet,2006,367(9518):1241-1246.DOI:10.1016/S0140-6736(06)68438-9.
22 Joseph DB,Borer JG,De Filippo RE,et al.Autologous cell seeded biodegradable scaffold for augmentation cystoplasty:phase II study in children and adolescents with spina bifida[J].J Urol,2014,191(15):1389-1395.DOI:10.1016/j.juro.2013.10.103.
23 Caione P,Boldrini R,Salerno A,et al.Bladder augmentation using acellular collagen biomatrix:a pilot experience in exstrophic patients[J].Pediatr Surg Int,2012,28(4):421-428.DOI:10.1007/s00383-012-3063-0.
24 Schaefer M,Kaiser A,Stehr M,et al.Bladder augmentation with small intestinal submucosa leads to unsatisfactory long term results[J].J Pediatr Urol,2013,9(6 Pt A):878-883.DOI:10.1016/j.jpurol.2012.12.001.
25 Zhang F,Liao L.Long-term follow-up of neurogenic bladder patients after bladder augmentation with small intestinal submucosa[J].World J Urol,2019.DOI:10.1007/s00345-019-03008-x.[Epub ahead of print]
26 Eastman R Jr,Leaf EM,Zhang D,et al.Fibroblast growth factor-10 signals development of von Brunn’s nests in the exstrophic bladder[J].Am J Physiol Renal Physiol,2010,299(5):F1094-F1110.DOI:10.1152/ajprenal.00056.2010.
27 Fossum M,Svensson J,Kratz G,et al.Autologous in vitro cultured urothelium in hypospadias repair[J].J Pediatr Urol,2007,3(1):10-18.DOI:10.1016/j.jpurol.2006.01.018.
28 Bhargava S,Patterson JM,Inman RD,et al.Tissue-engineered buccal mucosa urethroplasty-clinical outcomes[J].Eur Urol,2008,53(6):1263-1269.DOI:10.1016/j.eururo.2008.01.061.
29 Raya-Rivera A,Esquiliano DR,Yoo JJ,et al.Tissue-engineered autologous urethras for patients who need reconstruction:an observational study[J].Lancet,2011,377(9772):1175-1182.DOI:10.1016/S0140-6736(10)62354-9.
30 孙宁.关于提高尿道下裂手术技能的一些思考[J].临床小儿外科杂志,2018,17(8):561-563.DOI:10.3969/j.issn.1671-6353.2018.08.001. Sun N.Thoughts on refining surgical techniques for hypospadias[J].J Clin Ped Sur,2018,17(8):561-563.DOI:10.3969/j.issn.1671-6353.2018.08.001.
31 Lin HK,Cowan R,Moore P,et al.Characterization of neuropathic bladder smooth muscle cells in culture[J].J Urol,2004,171(3):1348-1352.DOI:10.1097/01.ju.0000108800.47594.8b.
32 Dozmorov MG,Kropp BP,Hurst RE,et al.Differentially expressed gene networks in cultured smooth muscle cells from normal and neuropathic bladder[J].J Smooth Muscle Res,2007,43(2):55-72.DOI:10.1540/jsmr.43.55.
33 Subramaniam R,Hinley J,Stahlschmidt J,et al.Tissue engineering potential of urothelial cells from diseased bladders[J].J Urol,2011,186(5):2014-2020.DOI:10.1016/j.juro.2011.07.031.
34 Laschke MW,Menger MD.Prevascularization in tissue engineering:Current concepts and future Directions[J].Biotechnol Adv,2016,34(2):112-121.DOI:10.1016/j.biotechadv.2015.12.004.
35 Utzinger U,Baggett B,Weiss JA,et al.Large-scale time series microscopy of neovessel growth during angiogenesis[J].Angiogenesis,2015,18(3):219-232.DOI:10.1007/s10456-015-9461-x.
36 Adamowicz J,Kuffel B,Van Breda SV,et al.Reconstructive urology and tissue engineering:Converging developmental paths[J].J Tissue Eng Regen Med,2019,13(3):522-533.DOI:10.1002/term.2812.
37 Horst M,Eberli D,Gobet R,et al.Tissue engineering in pediatric bladder reconstruction-the road to success[J].Front Pediatr,2019,7:91.DOI:10.3389/fped.2019.00091.
38 Mirzaii-Dizgah I,Salmanyan B.Renal function in a rat model of neurogenic bladder,effect of statins and phosphodiesterase-5 inhibitors[J].Eur Spine J,2013,22(12):2766-2769.DOI:10.1007/s00586-013-2927-x.
39 Lin D,Liu P,Wang G,et al.The distribution of Preputial vessels in different severity of rat congenital hypospadias model:imaging study using micro-computerized tomography[J].BMC Urol,2019,19(1):111.DOI:10.1186/s12894-019-0547-4.
40 Vasquez E,Cristofaro V,Lukianov S,et al.Deletion of neuropilin 2 enhances detrusor contractility following bladder outlet obstruction[J].JCI Insight,2017,2(3):e90617.DOI:10.1172/jci.insight.90617.
41 Farhat WA.Tissue engineering of the bladder-when will we get there?[J].J Urol,2014,192(4):1021-1022.DOI:10.1016/j.juro.2014.07.079.
42 Iannaccone PM,Galat V,Bury MI,et al.The utility of stem cells in pediatric urinary bladder regeneration[J].Pediatr Res,2018,83(1-2):258-266.DOI:10.1038/pr.2017.229.
43 Sharma AK,Hota PV,Matoka DJ,et al.Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films[J].Biomaterials,2010,31(24):6207-6217.DOI:10.1016/j.biomaterials.2010.04.054.
44 Sharma AK,Bury MI,Fuller NJ,et al.Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration[J].Proc Natl Acad Sci USA,2013,110(10):4003-4008.DOI:10.1073/pnas.1220764110.
45 Yudintceva NM,Nashchekina YA,Blinova MI,et al.Experimental bladder regeneration using a poly-l-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells[J].Int J Nanomedicine,2016,11:4521-4533.DOI:10.2147/IJN.S111656.
46 Zhe Z,Jun D,Yang Z,et al.Bladder acellular matrix grafts seeded with adipose-derived stem cells and incubated intraperitoneally promote the regeneration of bladder smooth muscle and nerve in arat model of bladder augmentation[J].Stem Cells Dev,2016,25(5):405-414.DOI:10.1089/scd.2015.0246.
47 Wan Q,Xiong G,Liu G,et al.Urothelium with barrier function differentiated from human urine-derived stem cells for potential use in urinary tract reconstruction[J].Stem Cell Res Ther,2018,9(1):304.DOI:10.1186/s13287-018-1035-6.
48 Jia Z,Guo H,Xie H,et al.Harvesting prevascularized smooth muscle cell sheets from common polystyrene culture dishes[J].PLoS ONE,2018,13(9):e0204677.DOI:10.1371/journal.pone.0204677.
49 Guduric V,Siadous R,Babilotte J,et al.Layer-by-layer bioassembly of poly(lactic) acid membranes loaded with coculture of HBMSCs and EPCs improves vascularization in vivo[J].J Biomed Mater Res A,2019,107(12):2629-2642.DOI:10.1002/jbm.a.36769.
50 Nguyen BB,Moriarty RA,Kamalitdinov T,et al.Collagen hydrogel scaffold promotes mesenchymal stem cell and endothelial cell coculture for bone tissue engineering[J].J Biomed Mater Res A,2017,105(4):1123-1131.DOI:10.1002/jbm.a.36008.
51 Zhou F,Zhang L,Chen L,et al.Prevascularized mesenchymal stem cell-sheets increase survival of random skin flaps in a nude mouse model[J].Am J Transl Res,2019,11(3):1403-1416.
52 Sekine H,Shimizu T,Sakaguchi K,et al.In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels[J].Nat Commun,2013,4:1399.DOI:10.1038/ncomms2406.
53 He J,Han X,Wang S,et al.Cell sheets of co-cultured BMP-2-modified bone marrow stromal cells and endothelial progenitor cells accelerate bone regeneration in vitro[J].Exp Ther Med,2019,18(5):3333-3340.DOI:10.3892/etm.2019.7982.
54 Yap KK,Yeoh GC,Morrison WA,et al.The Vascularised Chamber as an In Vivo Bioreactor[J].Trends Biotechnol,2018,36(10):1011-1024.DOI:10.1016/j.tibtech.2018.05.009.
55 Ding Y,Zhao AS,Liu T,et al.An injectable nanocomposite hydrogel for potential application of vascularization and tissue repair[J].Ann Biomed Eng,2020.DOI:10.1007/s10439-020-02471-7.[Epub ahead of print]
56 Abdullah MF,Nuge T,Andriyana A,et al.Core-shell fibers:design,roles,and controllable release strategies in tissue engineering and drug delivery[J].Polymers (Basel),2019,11(12):E2008.DOI:10.3390/polym11122008.
57 Nagase K,Nagumo Y,Kim M,et al.Local release of VEGF using fiber mats enables effective transplantation of layered cardiomyocyte sheets[J].Macromol Biosci,2017,17(8).DOI:10.1002/mabi.201700073.
58 Spiller KL,Freytes DO,Vunjak-Novakovic G.Macrophages modulate engineered human tissues for enhanced vascularization and healing[J].Ann Biomed Eng,2015,43(3):616-627.DOI:10.1007/s10439-014-1156-8.
59 Ley K.M1 means kill; M2 means heal[J].J Immunol,2017,199(7):2191-2193.DOI:10.4049/jimmunol.1701135.
60 Garg K,Pullen NA,Oskeritzian CA,et al.Macrophage functional polarization (M1/M2) in response tovarying fiber and pore dimensions of electrospun scaffolds[J].Biomaterials,2013,34(18):4439-4451.DOI:10.1016/j.biomaterials.2013.02.065.
61 Pokrywczynska M,Rasmus M,Jundzill A,et al.Mesenchymal stromal cells modulate the molecular pattern of healing process in tissue-engineered urinary bladder:the microarray data[J].Stem Cell Res Ther,2019,10(1):176.DOI:10.1186/s13287-019-1266-1.
相似文献/References:
[1]鲁中原 张建 张潍平 冀圆琦 李明磊 屈彦超. 脊髓脊膜膨出患儿尿动力学改变与上尿路损害的关系探讨[J].临床小儿外科杂志,2011,10(06):420.
[J].Journal of Clinical Pediatric Surgery,2011,10(04):420.
[2]李守林 刘晓东 姜俊海. 血浆和尿中内皮素、一氧化氮在神经源性膀胱中的检测及意义[J].临床小儿外科杂志,2014,13(06):488.
[3]吴少峰,何蓉,孙杰,等.组织工程补片在重度尿道下裂分期手术中的应用[J].临床小儿外科杂志,2018,17(08):577.
Wu Shaofeng,He Rong,Sun Jie,et al.Twostaged urethroplasty with tissueengineered graft for proximal hypospadias with severe chordee.[J].Journal of Clinical Pediatric Surgery,2018,17(04):577.
[4]张旭辉,罗添华,王计文,等.UPJO手术中双J管置入膀胱失败的危险因素分析[J].临床小儿外科杂志,2020,19(03):224.[doi:10.3969/j.issn.1671-6353.2020.03.007]
Zhang Xuhui,Luo Tianhua,Wang Jiwen,et al.Analysis of risk factors for failure of double J inserting into bladder during operation of ureteropelvic junction obstruction[J].Journal of Clinical Pediatric Surgery,2020,19(04):224.[doi:10.3969/j.issn.1671-6353.2020.03.007]
[5]曾甜,李新宁,黄晶晶,等.同种异体脱细胞真皮修补术治疗巨型脐膨出的疗效分析[J].临床小儿外科杂志,2020,19(04):306.[doi:10.3969/j.issn.1671-6353.2020.04.005]
Zeng Tian,Li Xinning,Huang Jingjing,et al.Efficacy of allogeneic acellular dermal mantrix in repairing giant omphalocele[J].Journal of Clinical Pediatric Surgery,2020,19(04):306.[doi:10.3969/j.issn.1671-6353.2020.04.005]
[6]石志康,张胜利,赵敏利,等.脂肪干细胞和血管内皮细胞共培养复合脱细胞基质材料修复兔尿道缺损的实验研究[J].临床小儿外科杂志,2020,19(04):310.[doi:10.3969/j.issn.1671-6353.2020.04.006]
Shi Zhikang,Zhang Shengli,Zhao Minli,et al.Repair of urethral defects in rabbits using adipose stem cells and vascular endothelial cells co-cultured with acellular matrix materials[J].Journal of Clinical Pediatric Surgery,2020,19(04):310.[doi:10.3969/j.issn.1671-6353.2020.04.006]
[7]陈峰,沈立.CorMatrix在心脏外科中的应用[J].临床小儿外科杂志,2020,19(04):321.[doi:10.3969/j.issn.1671-6353.2020.04.008]
Chen Feng,Shen Li.Application of CorMatrix in cardiac surgery[J].Journal of Clinical Pediatric Surgery,2020,19(04):321.[doi:10.3969/j.issn.1671-6353.2020.04.008]
[8]呼和,蒋飞,姬广春,等.光修复对脊髓栓系伴神经源性膀胱大鼠的作用研究[J].临床小儿外科杂志,2020,19(07):648.[doi:10.3969/j.issn.1671-6353.2020.07.017]
Hu He,Jiang Fei,Ji Guangchun,et al.Effect of light repair on spinal cord tether with neurogenic bladder in rats[J].Journal of Clinical Pediatric Surgery,2020,19(04):648.[doi:10.3969/j.issn.1671-6353.2020.07.017]
[9]杨丹,李明磊,谢向辉,等.盆底肌电图滞后时间诊断儿童特发性逼尿肌过度活跃的初步评价[J].临床小儿外科杂志,2020,19(11):981.[doi:10.3969/j.issn.1671-6353.2020.11.004]
Yang Dan,Li Minglei,Xie Xianghui,et al.A preliminary evaluation of pelvic floor electromyography lag time in the diagnosis of idiopathic detrusor overactivity disorder in children[J].Journal of Clinical Pediatric Surgery,2020,19(04):981.[doi:10.3969/j.issn.1671-6353.2020.11.004]
[10]李琦,蔡淼,吴盛德,等.神经源性膀胱上尿路损害的危险因素分析[J].临床小儿外科杂志,2022,21(03):253.[doi:10.3760/cma.j.cn101785-202108049-010]
Li Qi,Cai Miao,Wu Shengde,et al.Analysis of risk factors for upper urinary tract injury in children with neurogenic bladder[J].Journal of Clinical Pediatric Surgery,2022,21(04):253.[doi:10.3760/cma.j.cn101785-202108049-010]
备注/Memo
收稿日期:2020-01-12。
基金项目:国家自然科学基金(编号:81870459)
通讯作者:陈方,Email:doctorchenfang@126.com