摘要:细胞膜片技术是一种无支架的组织工程技术,主要通过调节细胞的培养温度获取连接紧密的活细胞组织片 与自分泌的细胞外基质,可以完整保留细胞表面的关键蛋白,如离子通道、生长因子受体、细胞间连接蛋白。由 于无需外源支架材料,能够避免排异及伦理等问题,可有效弥补现有修复材料的不足。通过检索近 5年的国内外 公开发表的文献,发现细胞膜片被广泛应用于泌尿系统疾病的治疗中,其具有独特的临床转化前景,但截止目前 尚未见相关主题的综述。细胞膜片在尿道与膀胱的修复、急慢性肾损伤、充盈性尿失禁等疾病中被证实有良好的 治疗效果,但是缺乏进一步的临床试验研究。目前尚未检索到利用细胞膜片修复输尿管的研究报道。此外,在细 胞膜片应用于临床之后即将面临细胞膜片的培养周期较长与择期手术的矛盾以及产业化问题。将来如何妥善保存 成熟的细胞膜片以做到随取随用也是一项充满挑战的研究方向。
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[1] JACKSON CJ, TONSETH KA, UTHEIM TP. Cultured epidermal stem cells in regenerative medicine [J]. Stem Cell Res Ther, 2017,8(1):1-7
[2] LI M, MA J, GAO Y, et al. Cell sheet technology: a promising strategy in regenerative medicine [J]. Cytotherapy, 2018,21(1):3-16
[3] PARK HJ, KONG MJ, JANG HJ, et al. A non- biodegradable scaffold- free cell sheet of genome- engineered mesenchymal stem cells inhibits development of acute kidney injury [J]. Kidney Int, 2021,99(1):117-133
[4] OKA M, SEKIYA S, SAKIYAMA R, et al. Hepatocyte Growth Factor- Secreting Mesothelial Cell Sheets Suppress Progressive Fibrosis in a Rat Model of CKD [J]. J Am Soc Nephrol, 2019,30(2):261-276
[5] LI J, CHEN S, UYAMA T, et al. Clinical Application of Cultured Stratified Epithelial Sheets Grown Under Feeder or Feeder- Free Conditions for Stable Vitiligo [J]. Dermatol Surg, 2019,45(4):497-505
[6] OLIVA J, BARDAG- GORCE F, NIIHARA Y, et al. Clinical Trials of Limbal Stem Cell Deficiency Treated with Oral Mucosal Epithelial Cells [J]. Int J Mol Sci, 2020,21(2):1-17
[7] KYM D, YIM H, YOON J, et al. The application of cultured epithelial autografts improves survival in burns [J]. Wound Repair Regen, 2015,23(3):340-344
[8] BARDAG GF, OLIVA J, WOOD A, et al. Carrier- free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) for corneal epithelium reconstruction: a histological study [J]. Ocul Surf, 2015,13(2):150-163
[9] BURILLON C, HUOT L, JUSTIN V, et al. Cultured autologous oral mucosal epithelial cell sheet (CAOMECS) transplantation for the treatment of corneal limbal epithelial stem cell deficiency [J]. Invest Ophthalmol Vis Sci, 2012, 53(3):1325-1331
[10] YAMAMOTO K, YAMATO M, MORINO T, et al. Middle ear mucosal regeneration by tissue- engineered cell sheet transplantation [J]. NPJ Regen Med, 2017,2(6):1-11
[11] YANG J, YAMATO M, SHIMIZU T, et al. Reconstruction of functional tissues with cell sheet engineering [J]. Biomaterials, 2007,28(34):5033-5043
[12] KIKUCHI A, OKUHARA M, KARIKUSA F, et al. Two- dimensional manipulation of confluently cultured vascular endothelial cells using temperature responsive poly (N- isopropylacrylamide) grafted surfaces [J]. J Biomater Sci Polym ed, 1998,9(12):1331-1348
[13] 郭海林,贾智明,鲍星奇,等.细胞膜片技术在组织工程中的应用 [J].中华细胞与干细胞杂志(电子版),2017,7(06):351-355
[14] KOBAYASHI J, KIKUCHI A, AOYAGI T, et al. Cell sheet tissue engineering: Cell sheet preparation, harvesting/ manipulation, and transplantation [J]. J Biomed Mater Res A, 2019,107(5):955-967
[15] 陈海琛,唐耘熳,徐延波,等.阴茎腹侧 Buck筋膜重建在重度尿道 下裂修复中的应用及近期疗效观察[J].临床小儿外科杂志,2019, 18(2):130-135
[16] 王泽宇,宋鲁杰,傅强.2020年美国泌尿外科学会年会尿道修复精 粹概要[J].临床泌尿外科杂志,2020,35(7):571-574
[17] MUNDY AR, ANDRICH DE. Urethral strictures [J]. BJU Int, 2011,107(1):6-26
[18] JIANG S, XU Z, ZHAO Y, et al. Urethral Reconstruction Using Mesothelial Cell- Seeded Autogenous Granulation Tissue Tube: An Experimental Study in Male Rabbits [J]. Biomed Res Int, 2017,2017(1850256):1-9
[19] KELLER H, BEIER J, DOBKOWICZ L. Long term results of reconstruction of recurrent urethral strictures with buccal mucosal graft [J]. Eur Urol, 2007,6(2):139-139
[20] YEUNG CK, AGGARWAL S, BUKUYNAL C, et al. The use of pedicled appendix graft for substitution of urethra in recurrent urethral stricture [J]. J Pediatr Surg, 2002, 37(2):246-250
[21] STAACK A, HAYWARD SW, BASKIN LS, et al. Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration [J]. Differentiation, 2005,73(4):121-133
[22] ROGOVAYA OS, FAYZULIN AK, VASILIEV AV, et al. Reconstruction of rabbit urethral epithelium with skin keratinocytes [J]. Acta Naturae, 2015,7(1):70-77
[23] ZHOU S, YANG R, ZOU Q, et al. Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling by Ultrasmall Superparamagnetic Iron Oxide for Full- Thickness Urethral Reconstruction [J]. Theranostics, 2017,7(9):2509-2523
[24] WANG Y, ZHOU S, YANG R, et al. Bioengineered bladder patches constructed from multilayered adipose- derived stem cell sheets for bladder regeneration [J]. Acta Biomater, 2019,85(2):131-141
[25] GUO HL, PENG XF, BAO XQ, et al. Bladder reconstruction using autologous smooth muscle cell sheets grafted on a pre-vascularized capsule [J]. Theranostics, 2020,10 (23):10378-10393
[26] WATANABE E, YAMATO M, SHIROYANAGI Y, et al. Bladder augmentation using tissue- engineered autologous oral mucosal epithelial cell sheets grafted on demucosalized gastric flaps [J]. Transplantation, 2011,91(7):700-706
[27] RONCO C, BELLOMO R, KELLUM JA. Acute kidney injury [J]. Lancet, 2019,394(10212):1949-1964
[28] HAN SJ, LEE HT. Mechanisms and therapeutic targets of ischemic acute kidney injury [J]. Kidney Res Clin Pract, 2019,38(4):427-440
[29] BARNES CJ, DISTASO CT, SPITZ KM, et al. Comparison of stem cell therapies for acute kidney injury [J]. Am J Stem Cells, 2016,5(1):1-10
[30] ZHU XY, LERMAN A, LERMAN LO. Concise review: mesenchymal stem cell treatment for ischemic kidney disease [J]. Stem Cells, 2013,31(9):1731-1736
[31] YOKOO T. Stem cell sheet therapy: another option for acute kidney injury [J]. Kidney Int, 2021,99(1):22-24
[32] 徐世豪,郭宁,陆赛,等.炎症与修复在肾移植术后的相互作用[J]. 泌尿外科杂志(电子版),2018,10(4):4-8
[33] MISSERI R, MELDRUM DR, DINARELLO CA, et al. TNF- α mediates obstruction- induced renal tubular cell apoptosis and proapoptotic signaling [J]. Am J Physiol Renal Physiol, 2005,288(2):406-411
[34] INOUE T, KOZAWA E, OKADA H, et al. Noninvasive evaluation of kidney hypoxia and fibrosis using magnetic resonance imaging [J]. J Am Soc Nephrol, 2011,22 (8):1429-1434
[35] HIGGINS DF, KIMURA K, BERNHARDT WM, et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial- to-mesenchymal transition [J]. J Clin Invest, 2007,117(12):3810-3820
[36] MATSUMOTO M, TANAKA T, YAMAMOTO T, et al. Hypoperfusion of peritubular capillaries induces chronic hy- poxia before progression of tubulointerstitial injury in a progressive model of rat glomerulonephritis [J]. J Am Soc Nephrol, 2004,15(6):1574-1581
[37] TANAKA S, TANAKA T, NANGAKU M. Hypoxia as a key player in the AKI- to- CKD transition [J]. Am J Physiol Renal Physiol, 2014,307(11):1187-1195
[38] NANGAKU M. Chronic hypoxia and tubulointerstitial injury: A final common pathway to end- stage renal failure [J]. J Am Soc Nephrol, 2006,17(1):17-25
[39] MIZUNO S, MATSUMOTO K, NAKAMURA T. Hepatocyte growth factor suppresses interstitial fibrosis in a mouse model of obstructive nephropathy [J]. Kidney Int, 2001,59(4):1304-1314
[40] HAYASHI S, MORISHITA R, NAKAMURA S, et al. Potential role of hepatocyte growth factor, a novel angiogenic growth factor, in peripheral arterial disease: Downregulation of HGF in response to hypoxia in vascular cells [J]. Circulation, 1999,100(19):11301-11308
[41] MORISHITA R, AOKI M, HASHIYA N, et al. Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease [J]. Hypertension, 2004,44(2):203-209
[42] KAGA T, KAWANO H, SAKAGUCHI M, et al. Hepatocyte growth factor stimulated angiogenesis without inflammation: Differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor [J]. Vascul Pharmacol, 2012,57(1):3-9
[43] MAKONDO K, KIMURA K, KITAMURA N, et al. Hepatocyte growth factor activates endothelial nitric oxide synthase by Ca(2 + )- and phosphoinositide 3- kinase/Aktdependent phosphorylation in aortic endothelial cells [J]. Biochem J, 2003,374(1):63-69
[44] FINISGUERRA V, DI CONZA G, DI MATTEO M, et al. MET is required for the recruitment of anti- tumoural neutrophils [J]. Nature, 2015,522(7556):349-353
[45] YANG J, LIU Y. Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis [J]. J Am Soc Nephrol, 2002,13(1): 96-107
[46] IDO A, MORIUCHI A, KIM I, et al. Pharmacokinetic study of recombinant human hepatocyte growth factor administered in a bolus intravenously or via portal vein [J]. Hepatol Res, 2004,30(3):175-181
[47] 王钞崎,刘春,双卫兵.压力性尿失禁再生医学疗法的研究进展[J]. 泌尿外科杂志(电子版),2019,11(04):23-28
[48] AP KLAUSNER, JM VAPNEK. Urinary incontinence in the geriatric population [J]. M t Sinai J Med, 2003,70(1): 54-61
[49] WANG Y, RAHMAN M, YANG M, et al. Use of bioactive extracellular matrix fragments as a urethral bulking agent to treat stress urinary incontinence [J]. Acta Biomater, 2020,117(11):156-166
[50] ZOU XH, ZHI YL, CHEN X, et al. Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence [J]. Biomaterials, 2010,31(18):4872-4879.
张东亮,邵佳亮,郭团结,等. 细胞膜片技术在泌尿系统疾病中的治疗应用进展[J]. 泌尿外科杂志(电子版),2021,13(2):54-58. DOI:10.3969/j.issn.1674-7410.2021.02.013.
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细胞膜片技术(cell sheet technology,CST)目 前主要被应用于组织工程修复领域,具有广阔的临 床应用前景[1,2] 。近年来,利用质粒转染、基因编辑 等技术对细胞进行改性后培养成细胞膜片,从而加 强了其因子分泌功能或使其分泌新的细胞因子,也 进一步拓展了细胞膜片的治疗手段[3,4] 。在临床治疗 中,干细胞膜片、上皮细胞膜片和心肌细胞膜片已 分别在皮肤、角膜、中耳黏膜和心肌修复的试验中 取得满意的疗效从而得以应用[5-10] 。在泌尿系统疾病 的治疗中,CST 在临床研究中同样有良好的修复效 果,临床应用潜力正在被不断发掘。因此,本文将 主要阐述 CST 在泌尿系统疾病治疗领域内应用的研 究进展。
1 CST 简介
2 CST 在尿道修复中的应用
3 CST 在膀胱修复中的应用
4 CST 在急慢性肾损伤 (acute kidney injury, AKI) 中的应用
5 CST 在尿失禁治疗中的应用
6 结语与展望
6 结语与展望
综上所述,细胞膜片是一项在组织工程修复领 域具有广泛应用前景的技术。细胞膜片无需酶消 化,可以直接收获具有自分泌细胞外基质的多层细 胞薄片,完整地保存离子通道、细胞因子感受器和 细胞因子受体等成分,有利于细胞活性的保持并减 少移植后细胞的损失及凋亡,已在临床多个学科中 成功应用。虽然细胞膜片在尿道与膀胱的修复中有 大量的临床前研究,但是尚未进一步开展临床试 验。截至目前,尚未检索到利用细胞膜片修复输尿 管的研究报道。细胞膜片疗法用于治疗急慢性肾损 伤的适应证范围及利弊仍然需要探讨与权衡。细胞 膜片用于治疗尿失禁是一个新兴的研究方向,展现出 良好的临床应用前景。此外,在细胞膜片应用于临床 之后即将面临细胞膜片较长的培养周期与择期手术 的矛盾以及产业化问题,将来如何妥善保存成熟的 细胞膜片,做到随取随用也是一项充满挑战的研究 方向。
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