Tracheal Replacement Therapy with a Stem Cell-Seeded Graft: Lessons from Compassionate Use Application of a GMP-Compliant Tissue-Engineered Medicine.
Martin J ElliottColin R ButlerAikaterini Varanou-JenkinsLeanne PartingtonCarla CarvalhoEdward SamuelClaire CrowleyPeggy LangeNicholas J HamiltonRobert Edward HyndsTahera AnsariPaul SibbonsAnja FierensClaire McLarenDerek RoebuckColin WallisNagarajan MuthialuRichard HewittDavid CrabbeSamuel M JanesPaolo de CoppiMark W LowdellMartin A BirchallPublished in: Stem cells translational medicine (2019)
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. Stem Cells Translational Medicine 2017;6:1458-1464.
Keyphrases
- stem cells
- cell therapy
- replacement therapy
- clinical trial
- primary care
- climate change
- escherichia coli
- single cell
- intensive care unit
- pseudomonas aeruginosa
- extracellular matrix
- liver failure
- artificial intelligence
- staphylococcus aureus
- combination therapy
- smoking cessation
- drug induced
- preterm birth
- quality improvement
- aortic dissection