Regeneration of a neoartery through a completely autologous acellular conduit in a minipig model: a pilot study

Regeneration of a neoartery through a completely autologous acellular conduit in a minipig model: a pilot study
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在小型猪模型中通过完全自体非细胞导管再生新动脉:一项试点研究

DOI:
10.1186/s12967-018-1763-5
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发表时间:
2019-01
影响因子:
7.4
通讯作者:
Xuefeng Qiu
Xuefeng Qiu
中科院分区:
医学2区
文献类型:
--
作者:
Tao Wang;Nianguo Dong;Huimin Yan;Sze Yue Wong;Wen Zhao;Kang Xu;Dong Wang;Song Li;Xuefeng Qiu

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背景血管移植广泛应用于冠状动脉搭桥术、血液透析、外周动脉搭桥术和先天性心脏病的治疗。利用各种合成和天然材料制备组织工程血管。在本研究中,我们研究了在小型猪体内的组织工程技术,以制备脱细胞的自体细胞外基质为基础的移植物,可用作小直径血管旁路手术的血管移植物。通过将特氟隆管嵌入雌性小型猪的皮下袋中来制造直径为3.9 mm的(n = 8,体重25-30 kg)持续4周。然后通过CHAPS脱细胞溶液将它们脱细胞。肝素通过Sulfo-NHS/EDC共价连接至脱细胞组织导管。我们将这些脱细胞的,完全自体的细胞外基质为基础的移植物植入到小型猪的颈动脉,然后在植入后1或2个月处死的猪,并评估通畅率和外植体组织学。结果1个月后,通畅率为100%(5/5),而移植物的内径为3.43 ± 0.05 mm(n = 5)。术后2个月通畅率为67%(2/3),血管内径为2.32 ± 0.14mm(n = 3)。组织学染色证实成功的细胞浸润,胶原蛋白和弹性蛋白沉积在2个月的样品。单层内皮细胞观察沿着内腔,而平滑肌细胞占主导地位的移植物wall.ConclusionA完全自体脱细胞导管具有优良的性能,在机械性能可以重塑成一个新的动脉在小型猪模型。在大型动物模型中进行的概念验证研究非常令人鼓舞,表明这是一个非常可行的想法,值得在临床转化之前在非人灵长类动物中进一步研究。
BackgroundVascular grafts are widely used as a treatment in coronary artery bypass surgery, hemodialysis, peripheral arterial bypass and congenital heart disease. Various types of synthetic and natural materials were experimented to produce tissue engineering vascular grafts. In this study, we investigated in vivo tissue engineering technology in miniature pigs to prepare decellularized autologous extracellular matrix-based grafts that could be used as vascular grafts for small-diameter vascular bypass surgery.MethodsAutologous tissue conduits (3.9 mm in diameter) were fabricated by embedding Teflon tubings in the subcutaneous pocket of female miniature pigs (n = 8, body weight 25–30 kg) for 4 weeks. They were then decellularized by CHAPS decellularization solution. Heparin was covalently-linked to decellularized tissue conduits by Sulfo-NHS/EDC. We implanted these decellularized, completely autologous extracellular matrix-based grafts into the carotid arteries of miniature pigs, then sacrificed the pigs at 1 or 2 months after implantation and evaluated the patency rate and explants histologically.ResultsAfter 1 month, the patency rate was 100% (5/5) while the inner diameter of the grafts was 3.43 ± 0.05 mm (n = 5). After 2 months, the patency rate was 67% (2/3) while the inner diameter of the grafts was 2.32 ± 0.14 mm (n = 3). Histological staining confirmed successful cell infiltration, and collagen and elastin deposition in 2-month samples. A monolayer of endothelial cells was observed along the inner lumen while smooth muscle cells were dominant in the graft wall.ConclusionA completely autologous acellular conduit with excellent performance in mechanical properties can be remodeled into a neoartery in a minipig model. This proof-of-concept study in the large animal model is very encouraging and indicates that this is a highly feasible idea worthy of further study in non-human primates before clinical translation.
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发表时间: 1998-07
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