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组织工程气道的临床移植

Clinical transplantation of a tissue-engineered airway.

作者信息

Macchiarini Paolo, Jungebluth Philipp, Go Tetsuhiko, Asnaghi M Adelaide, Rees Louisa E, Cogan Tristan A, Dodson Amanda, Martorell Jaume, Bellini Silvia, Parnigotto Pier Paolo, Dickinson Sally C, Hollander Anthony P, Mantero Sara, Conconi Maria Teresa, Birchall Martin A

机构信息

Department of General Thoracic Surgery, Hospital Clinic, Barcelona, Spain.

出版信息

Lancet. 2008 Dec 13;372(9655):2023-30. doi: 10.1016/S0140-6736(08)61598-6. Epub 2008 Nov 18.

Abstract

BACKGROUND

The loss of a normal airway is devastating. Attempts to replace large airways have met with serious problems. Prerequisites for a tissue-engineered replacement are a suitable matrix, cells, ideal mechanical properties, and the absence of antigenicity. We aimed to bioengineer tubular tracheal matrices, using a tissue-engineering protocol, and to assess the application of this technology in a patient with end-stage airway disease.

METHODS

We removed cells and MHC antigens from a human donor trachea, which was then readily colonised by epithelial cells and mesenchymal stem-cell-derived chondrocytes that had been cultured from cells taken from the recipient (a 30-year old woman with end-stage bronchomalacia). This graft was then used to replace the recipient's left main bronchus.

FINDINGS

The graft immediately provided the recipient with a functional airway, improved her quality of life, and had a normal appearance and mechanical properties at 4 months. The patient had no anti-donor antibodies and was not on immunosuppressive drugs.

INTERPRETATION

The results show that we can produce a cellular, tissue-engineered airway with mechanical properties that allow normal functioning, and which is free from the risks of rejection. The findings suggest that autologous cells combined with appropriate biomaterials might provide successful treatment for patients with serious clinical disorders.

摘要

背景

正常气道的丧失是毁灭性的。尝试替代大气道遇到了严重问题。组织工程替代物的先决条件是合适的基质、细胞、理想的机械性能和无抗原性。我们旨在使用组织工程方案生物工程化管状气管基质,并评估该技术在终末期气道疾病患者中的应用。

方法

我们从一名人类供体气管中去除细胞和主要组织相容性复合体(MHC)抗原,然后该气管很容易被从受体(一名30岁终末期支气管软化症女性)获取的细胞培养的上皮细胞和间充质干细胞来源的软骨细胞所定植。然后使用该移植物替代受体的左主支气管。

结果

该移植物立即为受体提供了功能性气道,改善了她的生活质量,并且在4个月时外观和机械性能正常。该患者没有抗供体抗体,也未服用免疫抑制药物。

解读

结果表明,我们可以制造出具有允许正常功能的机械性能且无排斥风险的细胞化组织工程气道。研究结果表明,自体细胞与合适的生物材料相结合可能为患有严重临床疾病的患者提供成功的治疗方法。

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