RETRACTED: Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study (Publication with Expression of Concern. See vol. 387, pg. 1359, 2016) (Retracted article. See vol. 392, pg. 11, 2018)

被引：312

作者：

Jungebluth, Philipp ^{[1
,8
]}

Alici, Evren ^{[2
]}

Baiguera, Silvia ^{[1
]}

Le Blanc, Katarina ^{[3
]}

Blomberg, Pontus ^{[9
]}

Bozoky, Bela ^{[10
]}

Crowley, Claire ^{[14
]}

Einarsson, Oskar ^{[15
]}

Grinnemo, Karl-Henrik ^{[1
,11
]}

Gudbjartsson, Tomas ^{[16
]}

Le Guyader, Sylvie ^{[4
]}

Henriksson, Gert ^{[8
]}

Hermanson, Ola ^{[5
]}

Juto, Jan Erik ^{[8
]}

Leidner, Bertil ^{[6
,12
]}

Lilja, Tobias ^{[5
]}

Liska, Jan ^{[11
]}

Luedde, Tom ^{[17
]}

Lundin, Vanessa ^{[7
]}

Moll, Guido ^{[3
]}

Nilsson, Bo ^{[18
]}

Roderburg, Christoph ^{[17
]}

Stromblad, Staffan ^{[4
]}

Sutlu, Tolga ^{[2
]}

Teixeira, Ana Isabel ^{[7
]}

Watz, Emma ^{[3
,13
]}

Seifalian, Alexander ^{[14
]}

Macchiarini, Paolo ^{[1
,8
]}

机构：

[1] Karolinska Inst, Adv Ctr Translat Regenerat Med, SE-14186 Stockholm, Sweden

[2] Karolinska Inst, Cell & Gene Therapy Ctr, Dept Med, Div Hematol, SE-14186 Stockholm, Sweden

[3] Karolinska Inst, Lab Med, SE-14186 Stockholm, Sweden

[4] Karolinska Inst, Ctr Biosci, Dept Biosci & Nutr, SE-14186 Stockholm, Sweden

[5] Karolinska Inst, Linnaeus Ctr Dev Biol Regenerat Med, Dept Neurosci, SE-14186 Stockholm, Sweden

[6] Karolinska Inst, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden

[7] Karolinska Inst, Dept Cell & Mol Biol, SE-14186 Stockholm, Sweden

[8] Karolinska Univ Hosp, Div Ear Nose & Throat, Stockholm, Sweden

[9] Karolinska Univ Hosp, Clin Res Ctr, Stockholm, Sweden

[10] Karolinska Univ Hosp, Div Pathol, Stockholm, Sweden

[11] Karolinska Univ Hosp, Dept Cardiothorac Surg & Anesthesiol, Stockholm, Sweden

[12] Karolinska Univ Hosp, Dept Radiol Huddinge, Stockholm, Sweden

[13] Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden

[14] UCL, Ctr Nanotechnol & Regenerat Med, London, England

[15] Univ Iceland, Landspitali Univ Hosp, Fac Med, Dept Pulmonol, Reykjavik, Iceland

[16] Univ Iceland, Landspitali Univ Hosp, Fac Med, Dept Cardiothorac Surg, Reykjavik, Iceland

[17] Univ Hosp RWTH Aachen, Dept Med 3, Aachen, Germany

[18] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden

来源：

LANCET | 2011年 / 378卷 / 9808期

基金：

瑞典研究理事会;

关键词：

AIRWAY COMPLICATIONS; MOBILIZATION; MANAGEMENT;

D O I：

10.1016/S0140-6736(11)61715-7

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. Methods A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 mu g/kg) and epoetin beta (40 000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. Findings We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after trans plantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Post-operatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Interpretation Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.

引用

页码：1997 / 2004

页数：8

共 28 条

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