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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

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Background. Malignant rhabdoid tumor (MRT), originally described as a rare renal sarcoma in childhood, has been known to express phenotypic diversity. In this study, unique characteristics of the MRT cells were investigated by using established cell lines. Methods. Immunocytochemical, ultrastructural, cytogenetic, and molecular (by polymerase chain reaction, PCR) analyses were done for two MRT cell lines, one of renal and one of extrarenal origin, before and after differentiation‐induction with either 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA) or transretinoic acid (RA). Results. The proliferating cells in the original tumor tissues as well as in the established cell lines demonstrated neural, epithelial, and mesenchymal markers morphologically. Both cell lines had karyotypic abnormalities including chromosome 22q11.2. The cell line from the extrarenal MRT, Tm87–16, demonstrated distinct morphologic changes with neuroblastic differentiation and produced numerous neuritic processes after treatment with either TPA or RA. The cell line from the renal MRT, STM91‐01, suggested schwannian differentiation but did not change morphologically after chemical induction. Both cell lines expressed c‐myc, but did not express N‐myc, MyoD1, tyrosine hydroxylase, or neural cell adhesion molecule (N‐CAM). With PCR and immunocytochemical study, a high level of chromogranin expression was detected by the cells of Tm87–16 only after TPA induced differentiation. Conclusions. MRT cells demonstrated diverse phenotype of neuro‐ecto‐mesenchymal differentiation. The results of this study suggest that MRT may be derived from a primitive pluripotential cell, such as neural crest or equivalent. MRT, therefore, might be categorized as one of the subsets of primitive neuroectodermal tumor.