Chinese Journal of Tissue Engineering Research ›› 2014, Vol. 18 ›› Issue (24): 3894-3899.doi: 10.3969/j.issn.2095-4344.2014.24.020
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Sun Yan-qi, Ma Jian-qun, Xu Hai
Revised:
2014-05-06
Online:
2014-06-11
Published:
2014-06-11
Contact:
Ma Jian-qun, M.D., Professor, Chief physician, Esophageal Mediastinal Ward, Department of Thoracic Surgery, Tumor Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China
About author:
Sun Yan-qi, Master, Esophageal Mediastinal Ward, Department of Thoracic Surgery, Tumor Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China
CLC Number:
Sun Yan-qi, Ma Jian-qun, Xu Hai . Progress in tissue-engineered trachea: breakthrough in cartilage and blood supply disorders[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(24): 3894-3899.
2.1 种子细胞 种子细胞可来源于自体、同种异体和异种组织[6]。气管组织工程支架材料通过适当的生物发生反应器,与培养的自体填充呼吸道上皮细胞和骨髓间充质干细胞衍生的软骨细胞,成功地替代患病主支气管[7]。 2.1.1 永生化人支气管上皮细胞 人支气管上皮细胞接种于胶原蛋白凝胶,该凝胶能够聚集肺成纤维祖细胞成三维结构。组织最初是浸没培养,然后升至气/液界面28 d培养。正常气管是由纤毛细胞、能够生成细胞黏蛋白的杯状细胞和基底上皮细胞组成。电子显微镜扫描能够直接发现纤毛细胞,组织学显示黏液生成细胞的存在,免疫组织化学抗p63和角蛋白14证实基底细胞的存在。这些结果表明,永生化人支气管上皮细胞保留分化的能力必须存在3种类型的物质:基质、黏蛋白产生、纤毛柱状上皮细胞[8]。 2.1.2 间充质干细胞 间充质干细胞具有很强的增殖分化潜能[9-11]。间充质干细胞在诱导条件下能够分化为软骨细胞。Go等[12]通过猪组织工程化气管实验证实了2个间充质干细胞来源的软骨细胞和上皮细胞的拟合必要性,以获得功能性和适当的长段气管移植的临床效果。这些发现和组织工程的应用方法将有助于推进人类受试者气管重建。 2.1.3 胚胎干细胞 胚胎在囊胚期前的发育阶段,胚泡的内细胞团和桑椹胚中部分细胞具有分化成各种组织器官的潜能,这部分细胞被称为胚胎干细胞。胚胎干细胞具有独特的高度未分化特性以及发育全能性,进一步形成全身各种组织器官的能力,得到组织工程研究学者的极大关注。 2.1.4 脂肪干细胞 近年来,脂肪干细胞是有应用价值的种子细胞,众多研究者将注意力集中于脂肪干细胞的应用研究领域[13-14]。目前研究已经证实,脂肪干细胞不仅可以向不同胚层来源的组织细胞分化,而且将这些细胞与合适的支架材料符合后,可以再体内构建不同的组织结构,包括骨、软骨、脂肪、心肌及血管组织[15]。为组织器官的缺损修复功能再建提供了良好的种子细胞。研究表明,脂肪干细胞在软骨诱导剂(转化生长因子β、地塞米松、胰岛素)中培养一段时间后,可以向软骨细胞分化[16]。 2.2 支架材料与软骨生成 对于气管组织工程来说,气管支架的生物化学、力学及结构特性具有非常重要的作用。引入合适的支架材料能够促进细胞沿着软骨方向分化并形成组织,从而有利于修复。理想情况下,构建体必须具有足够的刚性和柔韧性,长期通畅,并且是生物相容的,这因此需要在蜂窝和支架组件的优化的组织工程化气 管[17-18]。目前国际上应用于软骨组织工程研究的主要支架材料是聚酯类材料,以聚乳酸、聚乙醇酸以及两者的共聚物为主。但近年来的研究发现,这些材料仍存在生物相容性较差以及体内植入后酸性产物蓄积的现象,因此寻找其他新型细胞支架材料目前已经成为软骨组织工程研究的热点之一[19]。Shin等[20]报道同种异体软骨细胞的与猪软骨源性支架进行修补气管缺损,结果证实使用猪软骨源性支架与培养同种异体软骨细胞重建气管后恢复原形状和功能,没有任何排斥反应,支气管镜检查重建气管的任何溃烂或堵塞和缺陷完全覆盖再生呼吸道上皮。CT显示出气管良好的管腔轮廓。术后组织学数据表明,软骨细胞植入后产生较小的炎症反应和肉芽组织。 组织工程支架材料一般分为二为支架和三维支架,组织工程气管具有气管样的三维立体多孔结构,可以容纳细胞、细胞产物和细胞外基质,不会发生管壁塌陷及管体变形,并能保持一定的韧性,保证气管管状结构的通气功能。支架材料的形态和功能直接影响其所构成的组织形态和功能。 2.2.1 可降解高分子材料 主要为聚乳酸、聚羟基乙酸以及它们的聚合物聚乳酸羟基乙酸[21-22]。虽然可生物降解的三维支架材料如聚羟基乙酸纤维和聚乳酸纤维已被用于最各类工程气管软骨,但它们没有维持软骨的足够大小和支持气管形状的功能[23]。Sato等[24]报道在犬的动物模型上,应用胶原蛋白表面覆有聚合物,聚(L-乳酸-共ε-己内酯),结构显示,表面完全覆盖着复层纤毛柱状上皮或鳞状上皮无纤毛上皮细胞。从而证实了生物降解的聚合物涂层保护的胶原层,并促进更好上皮化:①支撑架材料的弹性及吸附性。组织工程支架都要求具有良好的生物相容性并能为组织体发展提供足够空间,其中支撑架材料的弹性及吸附性尤为重要,若支撑架材料与正常肺组织弹性存在明显差异将限制其正常生长,这与特发性肺纤维化或肉瘤样病患者瘢痕组织形成所致限制性肺疾病相类似。②支撑架多孔性[25]。所选材料应具有几何学上相互连接的微孔以促进组织吸收营养排出废物。③支撑架也必须提供足够的细胞表面积,以便于细胞播种、支撑架内细胞运动及随后的细胞吸附,同时有利于三维空间内细胞相互作用并促进细胞间信号传导。④肺组织结构的复杂性要求发展由多种材料构成的复合型支撑架[26]。 2.2.2 硅胶支架及胶原支架 组织工程化气管应用困难主要体现在:要涉及到气道狭窄(所造成的过度生长肉芽组织),气道塌陷(造成软骨软化)和黏液嵌塞(主要是由缺乏上皮引起的)。Luo等[27]报道采用硅胶支架在体外预培养和在体内植入能够成功地再生管状软骨的气管,有效的抑制肉芽增生,防止气道狭窄,从而极大地提高了生存率。最重要的是,通过肌肉内植入并移植带蒂肌皮瓣,建立血液供应稳定组织工程化气管移植,这保证维护管状软骨的结构和功能,组织工程化气管加速上皮移植和节段性缺损气管,从而实现长期功能重建。 2.2.3 葡聚糖凝胶及糖胺多糖 耳廓软骨中含有较多的葡萄糖胺聚糖和胶原,Whitney等[28]研究表明成熟扩增的耳廓软骨细胞能够长入微细钽孔中制备大型支架材料,因此耳廓软骨细胞衍生的在支架结构能够用于创建工程化气管模型。在兔动物模型上使用NVR-7薄膜的和硫酸葡聚糖凝胶衍生的共聚物构建的组织工程化气管修复气管缺损段,这种新薄膜的独特特点是生物相容性、生物可降解性、弹性和易于存储性[29]。Hong等[30]移植自体软骨细胞种植于纤维蛋白-透明质酸糖胺多糖形成的凝胶支架材料修补兔气管缺损,术后结果显示,植入支架完全覆盖着黏膜再生,并且无管腔狭窄。组织学上表现为移植物虽呈炎性反应的迹象,但表面覆着纤毛上皮,从而有利于气管功能的实现。 2.2.4 复合支架 不同种类的天然可降解高分子材料之间的复合,主要是为了从组分上尽可能的获得与细胞外基质相类似的组织工程支架。采用胶原-壳聚糖,壳聚糖-明胶、胶原-透明质酸等复合材料构建组织工程支架的研究已有报道。Komura等[31]探讨了在兔模型上种植自体软骨细胞于组织工程化气管可行性。自体软骨细胞种植到由胶原片、聚乙醇酸网和共聚物(L-丙交酯/ε-己内酯)组成的复合网格。该组织工程化复合物植入到颈段气管0.5 cm× 0.8 cm的缺损得以修复。 2.2.5 明胶海绵结合β-磷酸三钙 气管上皮再生是指气管管腔上皮细胞的增殖迁移,并且在支架的内部管腔有胶原蛋白附着。纤维化和软骨之间肉芽组织的再生是不利气管上皮再生的主要因素。组织工程化气管需要形成管腔结构,防止塌陷。Komura等[32]采用透明软骨细胞和耳廓产生的软骨细细胞种植于明胶海绵和β-磷酸三钙再造组织工程化气管。磷酸三钙具有良好的生物相容性、生物活性以及生物降解性, 是理想的人体硬组织修复和替代材料。β-磷酸三钙材料上软骨细胞能够正常生长,分化和繁殖。 2.2.6 纳米复合材料支架 纳米复合支架材料能够诱导细胞的再生及干细胞的分化,加强特定的生物活性剂和生长因子的利用。纳米技术应用到组织工程中产生的材料具有以下性能:①符合生物安全性。②良好的体内生物相容性和生物细胞有良好的相容性。③材料降解的科控性。④材料对组织的再生有良好的诱导性[33]。可见纳米技术在组织工程和未来性能更加优良的人工气管的制作拥有非常广泛的应用前景。 2.3 再血管化、血供及调节因子 2.3.1 促红细胞生成素及血管再生 促红细胞生成素是由肾脏和肝脏分泌的一种激素样物质,能够促进红细胞生成,能够增加组织工程化气管的血液供应,促进其血管 化[34]。促红细胞生成素可以提高组织内细胞的存活率。在许多体外和体内试验研究表明,成纤维细胞合成的细胞外基质分子对增殖内皮细胞生成血管非常重要。纤维连接蛋白、血小板凝血酶敏感蛋白、透明质酸和层黏连蛋白对细胞迁移、正常内皮细胞形成以及这些分子的内皮细胞表达受体有重要作用。 2.3.2 带蒂大网膜瓣 气管不具有单独的供血动脉及引流静脉,其血供来源与甲状腺和食管周围组织的毛细血管网。上半部分气管的血液供应来源与甲状腺下动脉和食管动脉分支,气管隆突和下半部分的气管血供来源于支气管动脉。为了促进组织工程气管的再血管化,应用带蒂大网膜瓣帮助移植物进行血运重建[35]。观察发现血流迅速恢复和管腔黏膜出现,从而证实附着种子上皮细胞和软骨细胞的生物假体植入前,带蒂大网膜瓣已经引起早期血运重建的可能性。 2.3.3 转化生长因子 转化生长因子是指两类多肽类生长因子, 转化生长因子α和转化生长因子β。转化生长因子α是由巨噬细胞,脑细胞和表皮细胞产生,可诱导上皮发育。人类转化生长因子β有3个亚型,转化生长因子β1、转化生长因子β2、转化生长因子β3。转化生长因子β是一个多功能蛋白质,可以影响多种细胞的生长,分化、细胞凋亡及免疫调节等功能[36]。多肽类生长因子是强有力的细胞行为调节剂,可调节细胞的增殖、迁移、分化及蛋白质表达。并且在组织再生中有治疗作用。常用的生长因子有成纤维生长因子、转化生长因子、胰岛素样生长因子、血小板衍化生长因子等。这些因子对组织器官正常功能的维持起着至关重要的作用。三维模型中,生长因子能够影响细胞与细胞基质和细胞与细胞相互作用。成纤维细胞生长因子能够Ⅲ型和Ⅳ型胶原主要集中在附近上皮和下降远离上皮。转化生长因子β1能够使上皮发挥促纤维化介质的作用,导致基质重塑[37]。 Kojima等[38]报道转化生长因子转化生长因子β1、转化生长因子β2和转化生长因子β3具有诱导软骨细胞分化的软骨细胞和间充质干能力细胞;然而,不具有相等的效果。转化生长因子β2和转化生长因子β3比转化生长因子β1更能促进软骨形成,导致了多于2倍糖胺聚糖积累和Ⅱ型胶原的沉积。将生长因子直接加入到损伤的组织促进细胞分化及增殖是最简单的方法,然而直接将生长因子注入是无效的,因为在1 d之内,生长因子将被很快的弥散及降解,目前已经开发了多种生长因子可控释系统,能够解决此问题。 2.3.4 前列腺素 前列腺素在体内由花生四烯酸所合成,结构为一个5环和两条侧链构成的20碳不饱和脂肪酸。前列腺素在组织工程化气管中的主要作用是: 细胞黏附、迁移、增殖和细胞外基质组装。因此,前列腺素和聚糖在调节细胞外基质中发挥着重要的调节作用。 Hinderer等[39]报道当形成脱细胞基质,消耗细胞结合的前列腺素和聚糖。前列腺素和聚糖的损失对细胞外基质的结构和完整性有重要影响,这最终影响到植入物的性能和耐用性。"
[1] Hamilton N, Bullock AJ, Macneil S, et al. Tissue engineering airway mucosa: A systematic review. Laryngoscope. 2014; 124(4):961-968. [2] Curcio E, Macchiarini P, De Bartolo L. Oxygen mass transfer in a human tissue-engineered trachea. Biomaterials. 2010; 31(19):5131-5136. [3] Delaere PR, Hermans R. Clinical transplantation of a tissue-engineered airway. Lancet. 2009;373(9665):717-718. [4] Unwin N, Guariguata L, Whiting D, et al. Complementary approaches to estimation of the global burden of diabetes. Lancet. 2012;379(9825):1487-1488. [5] Martinod E, Seguin A, Radu DM, et al. Airway transplantation: a challenge for regenerative medicine. Eur J Med Res. 2013; 18:25. [6] Kojima K, Bonassar LJ, Roy AK, et al. autologous tissue-engineered trachea with sheep nasal chondrocytes. J Thorac Cardiovasc Surg. 2002;123(6):1177-1184. [7] Alberti C. Tissue engineering as innovative chance for organ replacement in radical tumor surgery. Eur Rev Med Pharmacol Sci. 2013;17(5):6246-6231. [8] Vaughan MB, Ramirez RD, Wright WE, et al. A three-dimensional model of differentiation of immortalized human bronchial epithelial cells. Differentiation. 2006;74(4): 141-148. [9] 谭荣邦,史宏灿.间充质干细胞构建组织工程化气管的研究与应用[J].中国组织工程研究, 2013,17(10):1884-1890. [10] Naito H, Tojo T, Kimura M, et al. Engineering bioartificial tracheal tissue using hybrid fibroblast-mesenchymal stem cell cultures in collagen hydrogels. Interact Cardiovasc Thorac Surg. 2011;12(2):156-161. [11] Gustafsson Y, Haag J, Jungebluth P, et al. Viability and proliferation of rat MSCs on adhesion protein-modified PET and PU scaffolds. Biomaterials. 2012;33(32):8094-8103. [12] Go T, Jungebluth P, Baiguero S, et al. Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs. J Thorac Cardiovasc Surg. 2010;139(2):437-443. [13] Martínez-González I, Moreno R, Petriz J, et al. Engraftment potential of adipose tissue-derived human mesenchymal stem cells after transplantation in the fetal rabbit. Stem Cells Dev. 2012;21(18):3270-3277. [14] Hashemibeni B, Goharian V, Esfandiari E, et al. An animal model study for repair of tracheal defects with autologous stem cells and differentiated chondrocytes from adipose-derived stem cells. J Pediatr Surg. 2012;47(11):1997-2003. [15] Kobayashi K, Suzuki T, Nomoto Y, et al. A tissue-engineered trachea derived from a framed collagen scaffold, gingival fibroblasts and adipose-derived stem cells. Biomaterials. 2010;31(18):4855-4863. [16] Zang M, Zhang Q, Chang EI, et al. Decellularized tracheal matrix scaffold for tracheal tissue engineering: in vivo host response. Plast Reconstr Surg. 2013;132(4):549-559. [17] Hashemibeni B, Goharian V, Esfandiari E, et al. An animal model study for repair of tracheal defects with autologous stem cells and differentiated chondrocytes from adipose-derived stem cells. J Pediatr Surg. 2012;47(11):1997-2003. [18] Gilpin DA, Weidenbecher MS, Dennis JE. Scaffold-free tissue-engineered cartilage implants for laryngotracheal reconstruction. Laryngoscope. 2010;120(3):612-617. [19] Jungebluth P, Alici E, Baiguera S, et al. Tracheobronchial transplantation with a stem-cell-seeded bioartifi cial nanocomposite: a proof-of-concept study. Lancet. 2011; 378(9808):1997-2004. [20] Shin YS, Lee BH, Choi JW, et al. Tissue-engineered tracheal reconstruction using chondrocyte seeded on a porcine cartilage-derived substance scaffold. Int J Pediatr Otorhinolaryngol. 2014;78(1):32-38. [21] Cortiella J, Nichols JE, Kojima K, et al. Tissue-engineered lung: an in vivo and in vitro comparison of polyglycolic acid and pluronic F-127 hydrogel/somatic lung progenitor cell constructs to support tissue growth. Tissue Eng. 2006;12(5):1213-1225. [22] Kamil SH, Eavey RD, Vacanti MP, et al. Tissue-engineered cartilage as a graft source for laryngotracheal reconstruction: a pig model. Arch Otolaryngol Head Neck Surg. 2004;130(9): 1048-1051. [23] Tani G, Usui N, Kamiyama M, et al. In vitro construction of scaffold-free cylindrical cartilage using cell sheet-based tissue engineering. Pediatr Surg Int. 2010;26(2):179-185. [24] Sato T, Araki M, Nakajima N, et al. Biodegradable polymer coating promotes the epithelization of tissue-engineered airway prostheses. J Thorac Cardiovasc Surg. 2010;139(1):26-31. [25] Sato T, Nakamura T. Tissue-engineered airway replacement. Lancet. 2008;372(9655):2003-2004. [26] Chang JW, Park SA, Park JK, et al. Tissue-Engineered Tracheal Reconstruction Using Three-Dimensionally Printed Artificial Tracheal Graft: Preliminary Report. Artif Organs. 2014. [27] Luo X, Liu Y, Zhang Z, et al. Long-term functional reconstruction of segmental tracheal defect by pedicled tissue-engineered trachea in rabbits. Biomaterials. 2013; 34(13):3336-3344. [28] Whitney GA, Mera H, Weidenbecher M, et al. Methods for producing scaffold-free engineered cartilage sheets from auricular and articular chondrocyte cell sources and attachment to porous tantalum. Biores Open Access. 2012;1(4):157-165. [29] Klin B, Weinberg M, Vinograd I, et al. Experimental repair of tracheal defects using a new biodegradable membrane. J Laparoendosc Adv Surg Tech A. 2007;17(3):342-349. [30] Hong HJ, Lee JS, Choi JW, et al. Transplantation of autologous chondrocytes seeded on a fibrin/hyaluronan composite gel into tracheal cartilage defects in rabbits: preliminary results. Artif Organs. 2012;36(11):998-1006. [31] Komura M, Komura H, Kanamori Y, et al. An animal model study for tissue-engineered trachea fabricated from a biodegradable scaffold using chondrocytes to augment repair of tracheal stenosis. J Pediatr Surg. 2008;43(12):2141-2146. [32] Komura M, Komura H, Otani Y, et al. The junction between hyaline cartilage and engineered cartilage in rabbits. Laryngoscope. 2013;123(6):1547-1551. [33] Shi H, Wang W, Lu D, et al. Cellular biocompatibility and biomechanical properties of N-carboxyethylchitosan/ nanohydroxyapatite composites for tissue-engineered trachea. Artif Cells Blood Substit Immobil. Biotechnol. 2012;40(1-2): 120-124. [34] Elliott MJ, De Coppi P, Speggiorin S, et al. Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study. Lancet. 2012;380(9846):994-1000. [35] Tsugawa C, Nishijima E, Muraji T, et al. The use of omental pedicle flap for tracheobronchial reconstruction in infants and children. J Pediatr Surg. 1991;26(7):762-765. [36] Choe MM, Sporn PH, Swartz MA. Extracellular matrix remodeling by dynamic strain in a three-dimensional tissue-engineered human airway wall model. Am J Respir Cell Mol Biol. 2006;35(3):306-313. [37] Zani BG, Kojima K, Vacanti CA, et al. Tissue-engineered endothelial and epithelial implants differentially and synergistically regulate airway repair. Proc Natl Acad Sci U S A. 2008;105(19):7046-7051. [38] Kojima K, Ignotz RA, Kushibiki T, et al. Tissue-engineered trachea from sheep marrow stromal cells with transforming growth factor beta2 released from biodegradable microspheres in a nude rat recipient. J Thorac Cardiovasc Surg. 2004;128(1):147-153. [39] Hinderer S, Schenke-Layland K. Tracheal tissue engineering: building on a strong foundation. Expert Rev Med Devices. 2013;10(1):33-35. [40] Steger V, Hampel M, Trick I, et al. Clinical tracheal replacement: transplantation, bioprostheses and artificial grafts. Expert Rev Med Devices. 2008;5(5):605-612. [41] Walles T. Tracheobronchial bio-engineering Biotechnology fulfilling unmet medical needs. Adv Drug Deliv Rev. 2011;63: 367-374. [42] 章方彪,张卫东,史宏灿.脱细胞基质在组织工程气管移植中的研究进展[J].中国修复重建外科杂志, 2013,27(2):223-226. [43] Zang M, Zhang Q, Chang EI, et al. Decellularized tracheal matrix scaffold for tracheal tissue engineering: in vivo host response. Plast Reconstr Surg. 2013;132(4):549-559. [44] Vrana NE, Lavalle P, Dokmeci MR, et al. Engineering functional epithelium for regenerative medicine and in vitro organ models: a review. Tissue Eng Part B Rev. 2013;19(6):529-543. [45] Partington L, Mordan NJ, Mason C, et al. Biochemical changes caused by decellularization may compromise mechanical integrity of tracheal scaffolds. Acta Biomater. 2013;9(2):5251-5261. |
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