Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold.
Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold.
复制标题
成功植入由人体细胞和壳聚糖支架组成的工程管状神经肌肉组织。
DOI：
10.1016/j.surg.2015.05.009
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发表时间：
2015
期刊：
影响因子：
3.8
通讯作者：
Bitar,KhalilN
中科院分区：
文献类型：
--
作者：
Zakhem,Elie;Elbahrawy,Mostafa;Orlando,Giuseppe;Bitar,KhalilN
背景胃肠道大部分切除后，迫切需要肠延长术。在这项研究中，我们建议评估的重塑，血管化，和功能的壳聚糖为基础的，管状的神经肌肉组织皮下植入在背部的无胸腺rates.MethodsAligned神经支配的平滑肌片进行生物工程与人类平滑肌和神经祖细胞的使用。将神经支配的片包裹在管状壳聚糖支架周围。将工程化管状神经肌肉组织植入无胸腺大鼠背部皮下。种植体收获后14天，评估形态，血管化，和functionals.ResultsGross检查的种植体显示健康的颜色，没有炎症的迹象。大体和组织学分析表明，植入组织血管化。壳聚糖支持组织的管腔通畅性。受神经支配的肌肉在管状壳聚糖支架周围重塑。平滑肌保持其圆周排列和收缩表型。通过使用实时力生成进一步表征植入物的功能。胆碱能反应表现为对乙酰胆碱的强烈收缩。血管活性肠肽和电场刺激引起的松弛。在神经毒素河豚毒素的存在下，乙酰胆碱诱导的收缩和血管活性肠肽诱导的松弛的幅度衰减，而电场刺激诱导的松弛被完全废除，表明神经元的贡献response.ConclusionOur的结果表明成功的皮下植入工程管状神经肌肉组织。组织变得血管化并保持其肌源性和神经源性表型和功能，这为提供用于治疗GI运动障碍的可植入替代GI节段提供了潜在的治疗前景。
BackgroundThere is an urgent need for gut lengthening secondary to massive resections of the gastrointestinal tract. In this study, we propose to evaluate the remodeling, vascularization, and functionality of a chitosan-based, tubular neuromuscular tissue on subcutaneous implantation in the back of athymic rats.MethodsAligned innervated smooth muscle sheets were bioengineered with the use of human smooth muscle and neural progenitor cells. The innervated sheets were wrapped around tubular chitosan scaffolds. The engineered tubular neuromuscular tissue was implanted subcutaneously in the back of athymic rats. The implant was harvested after 14 days and assessed for morphology, vascularization, and functionality.ResultsGross examination of the implants showed healthy color with no signs of inflammation. The implanted tissue became vascularized as demonstrated by gross and histologic analysis. Chitosan supported the luminal patency of the tissue. The innervated muscle remodeled around the tubular chitosan scaffold. Smooth muscle maintained its circumferential alignment and contractile phenotype. The functionality of the implant was characterized further by the use of real-time force generation. A cholinergic response was demonstrated by robust contraction in response to acetylcholine. Vasoactive intestinal peptide-, and electrical field stimulation–caused relaxation. In the presence of neurotoxin tetrodotoxin, the magnitude of acetylcholine-induced contraction and vasoactive intestinal peptide-induced relaxation was attenuated whereas electrical field stimulation–induced relaxation was completely abolished, indicating neuronal contribution to the response.ConclusionOur results indicated the successful subcutaneous implantation of engineered tubular neuromuscular tissues. The tissues became vascularized and maintained their myogenic and neurogenic phenotype and function, which provides potential therapeutic prospects for providing implantable replacement GI segments for treating GI motility disorders.