Tracheal replacement therapy with a stem cell-seeded graft

Lessons from compassionate use application of a GMP-compliant tissue-engineered medicine

Martin J. Elliott, Colin R. Butler, Aikaterini Varanou-Jenkins, Leanne Partington, Carla Carvalho, Edward Samuel, Claire Crowley, Peggy Lange, Nicholas J. Hamilton, Robert E. Hynds, Tahera Ansari, Paul Sibbons, Anja Fierens, Claire McLaren, Derek Roebuck, Colin Wallis, Nagarajan Muthialu, Richard Hewitt, David Crabbe, Sam M. Janes & 3 others Paolo De Coppi, Mark W. Lowdell, Martin A. Birchall

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use of tissue-engineered tracheae in compassionate use cases suggests that such an approach is a viable option. Here, a stem cell-seeded, decellularized tissue-engineered tracheal graft was used on a compassionate basis for a girl with critical tracheal stenosis after conventional reconstructive techniques failed. The graft represents the first cell-seeded tracheal graft manufactured to full good manufacturing practice (GMP) standards. We report important preclinical and clinical data from the case, which ended in the death of the recipient. Early results were encouraging, but an acute event, hypothesized to be an intrathoracic bleed, caused sudden airway obstruction 3 weeks post-transplantation, resulting in her death. We detail the clinical events and identify areas of priority to improve future grafts. In particular, we advocate the use of stents during the first few months post-implantation. The negative outcome of this case highlights the inherent difficulties in clinical translation where preclinical in vivo models cannot replicate complex clinical scenarios that are encountered. The practical difficulties in delivering GMP grafts underscore the need to refine protocols for phase I clinical trials.

Original languageEnglish (US)
Pages (from-to)1458-1464
Number of pages7
JournalStem cells translational medicine
Volume6
Issue number6
DOIs
StatePublished - 2017
Externally publishedYes

Fingerprint

Compassionate Use Trials
Stem Cells
Medicine
Transplants
Tracheal Stenosis
Therapeutics
Clinical Trials, Phase I
Airway Obstruction
Trachea
Stents
Transplantation

Keywords

  • Bioartificial organs
  • Bioengineering
  • Regenerative medicine
  • Tissue engineering
  • Tissue scaffolds
  • Trachea

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Tracheal replacement therapy with a stem cell-seeded graft : Lessons from compassionate use application of a GMP-compliant tissue-engineered medicine. / Elliott, Martin J.; Butler, Colin R.; Varanou-Jenkins, Aikaterini; Partington, Leanne; Carvalho, Carla; Samuel, Edward; Crowley, Claire; Lange, Peggy; Hamilton, Nicholas J.; Hynds, Robert E.; Ansari, Tahera; Sibbons, Paul; Fierens, Anja; McLaren, Claire; Roebuck, Derek; Wallis, Colin; Muthialu, Nagarajan; Hewitt, Richard; Crabbe, David; Janes, Sam M.; De Coppi, Paolo; Lowdell, Mark W.; Birchall, Martin A.

In: Stem cells translational medicine, Vol. 6, No. 6, 2017, p. 1458-1464.

Research output: Contribution to journalArticle

Elliott, MJ, Butler, CR, Varanou-Jenkins, A, Partington, L, Carvalho, C, Samuel, E, Crowley, C, Lange, P, Hamilton, NJ, Hynds, RE, Ansari, T, Sibbons, P, Fierens, A, McLaren, C, Roebuck, D, Wallis, C, Muthialu, N, Hewitt, R, Crabbe, D, Janes, SM, De Coppi, P, Lowdell, MW & Birchall, MA 2017, 'Tracheal replacement therapy with a stem cell-seeded graft: Lessons from compassionate use application of a GMP-compliant tissue-engineered medicine', Stem cells translational medicine, vol. 6, no. 6, pp. 1458-1464. https://doi.org/10.1002/sctm.16-0443
Elliott, Martin J. ; Butler, Colin R. ; Varanou-Jenkins, Aikaterini ; Partington, Leanne ; Carvalho, Carla ; Samuel, Edward ; Crowley, Claire ; Lange, Peggy ; Hamilton, Nicholas J. ; Hynds, Robert E. ; Ansari, Tahera ; Sibbons, Paul ; Fierens, Anja ; McLaren, Claire ; Roebuck, Derek ; Wallis, Colin ; Muthialu, Nagarajan ; Hewitt, Richard ; Crabbe, David ; Janes, Sam M. ; De Coppi, Paolo ; Lowdell, Mark W. ; Birchall, Martin A. / Tracheal replacement therapy with a stem cell-seeded graft : Lessons from compassionate use application of a GMP-compliant tissue-engineered medicine. In: Stem cells translational medicine. 2017 ; Vol. 6, No. 6. pp. 1458-1464.
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