Stem-cell-based, tissue engineered tracheal replacement in a child: A 2-year follow-up study

Martin J. Elliott, Paolo De Coppi, Simone Speggiorin, Derek Roebuck, Colin R. Butler, Edward Samuel, Claire Crowley, Clare McLaren, Anja Fierens, David Vondrys, Lesley Cochrane, Christopher Jephson, Samuel Janes, Nicholas J. Beaumont, Tristan Cogan, Augustinus Bader, Alexander M. Seifalian, J. Justin Hsuan, Mark W. Lowdell, Martin A. Birchall

Research output: Contribution to journalArticle

283 Citations (Scopus)

Abstract

Background Stem-cell-based, tissue engineered transplants might off er new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaff old with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report fi ndings after 2 years of follow-up. Methods A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaff old was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaff old, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. Findings The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the fi rst 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. Interpretation Follow-up of the fi rst paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. Funding Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.

Original languageEnglish (US)
Pages (from-to)994-1000
Number of pages7
JournalThe Lancet
Volume380
Issue number9846
DOIs
StatePublished - Sep 2012
Externally publishedYes

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varespladib methyl
Stem Cells
Transplants
Erythropoietin
Epithelium
Chondrogenesis
compound A 12
Transforming Growth Factors
Granulocyte Colony-Stimulating Factor
Mesenchymal Stromal Cells
Proteomics
Stents
Ventilation
Cell Biology
Neutrophils
Thorax
Perfusion
Bone Marrow
Metals
Tissue Donors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Elliott, M. J., De Coppi, P., Speggiorin, S., Roebuck, D., Butler, C. R., Samuel, E., ... Birchall, M. A. (2012). Stem-cell-based, tissue engineered tracheal replacement in a child: A 2-year follow-up study. The Lancet, 380(9846), 994-1000. https://doi.org/10.1016/S0140-6736(12)60737-5

Stem-cell-based, tissue engineered tracheal replacement in a child : A 2-year follow-up study. / Elliott, Martin J.; De Coppi, Paolo; Speggiorin, Simone; Roebuck, Derek; Butler, Colin R.; Samuel, Edward; Crowley, Claire; McLaren, Clare; Fierens, Anja; Vondrys, David; Cochrane, Lesley; Jephson, Christopher; Janes, Samuel; Beaumont, Nicholas J.; Cogan, Tristan; Bader, Augustinus; Seifalian, Alexander M.; Hsuan, J. Justin; Lowdell, Mark W.; Birchall, Martin A.

In: The Lancet, Vol. 380, No. 9846, 09.2012, p. 994-1000.

Research output: Contribution to journalArticle

Elliott, MJ, De Coppi, P, Speggiorin, S, Roebuck, D, Butler, CR, Samuel, E, Crowley, C, McLaren, C, Fierens, A, Vondrys, D, Cochrane, L, Jephson, C, Janes, S, Beaumont, NJ, Cogan, T, Bader, A, Seifalian, AM, Hsuan, JJ, Lowdell, MW & Birchall, MA 2012, 'Stem-cell-based, tissue engineered tracheal replacement in a child: A 2-year follow-up study', The Lancet, vol. 380, no. 9846, pp. 994-1000. https://doi.org/10.1016/S0140-6736(12)60737-5
Elliott MJ, De Coppi P, Speggiorin S, Roebuck D, Butler CR, Samuel E et al. Stem-cell-based, tissue engineered tracheal replacement in a child: A 2-year follow-up study. The Lancet. 2012 Sep;380(9846):994-1000. https://doi.org/10.1016/S0140-6736(12)60737-5
Elliott, Martin J. ; De Coppi, Paolo ; Speggiorin, Simone ; Roebuck, Derek ; Butler, Colin R. ; Samuel, Edward ; Crowley, Claire ; McLaren, Clare ; Fierens, Anja ; Vondrys, David ; Cochrane, Lesley ; Jephson, Christopher ; Janes, Samuel ; Beaumont, Nicholas J. ; Cogan, Tristan ; Bader, Augustinus ; Seifalian, Alexander M. ; Hsuan, J. Justin ; Lowdell, Mark W. ; Birchall, Martin A. / Stem-cell-based, tissue engineered tracheal replacement in a child : A 2-year follow-up study. In: The Lancet. 2012 ; Vol. 380, No. 9846. pp. 994-1000.
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abstract = "Background Stem-cell-based, tissue engineered transplants might off er new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaff old with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report fi ndings after 2 years of follow-up. Methods A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaff old was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaff old, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. Findings The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the fi rst 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. Interpretation Follow-up of the fi rst paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. Funding Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.",
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T2 - A 2-year follow-up study

AU - Elliott, Martin J.

AU - De Coppi, Paolo

AU - Speggiorin, Simone

AU - Roebuck, Derek

AU - Butler, Colin R.

AU - Samuel, Edward

AU - Crowley, Claire

AU - McLaren, Clare

AU - Fierens, Anja

AU - Vondrys, David

AU - Cochrane, Lesley

AU - Jephson, Christopher

AU - Janes, Samuel

AU - Beaumont, Nicholas J.

AU - Cogan, Tristan

AU - Bader, Augustinus

AU - Seifalian, Alexander M.

AU - Hsuan, J. Justin

AU - Lowdell, Mark W.

AU - Birchall, Martin A.

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N2 - Background Stem-cell-based, tissue engineered transplants might off er new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaff old with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report fi ndings after 2 years of follow-up. Methods A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaff old was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaff old, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. Findings The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the fi rst 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. Interpretation Follow-up of the fi rst paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. Funding Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.

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