Stem-Cell-Seeded Bioartificial Tracheal Transplant Feasible

First-in-man bioengineered artificial tracheobronchial airway transplantation successful

THURSDAY, Nov. 24 (HealthDay News) -- A stem-cell-seeded bioartificial nanocomposite tracheobronchial scaffold can be used successfully to replace a complex airway defect, according to a proof-of-concept study published online Nov. 24 in The Lancet.

Philipp Jungebluth, M.D., from the Karolinska Intitutet in Stockholm, Sweden, and colleagues reported the outcome of a clinical transplantation of the tracheobronchial airway, made from a stem-cell-seeded bioartificial nanocomposite, in a 36-year-old male patient. The patient, who had previously been treated with debulking surgery and radiation, presented with recurrent primary cancer of the distal trachea and main bronchi. Following tumor resection, a tailored bioartificial nanocomposite, previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 hours, was used to replace the airway. Over a period of 14 days, postoperative granulocyte colony-stimulating factor filgrastim and epoetin beta, were given to enhance the regenerative process. Analyses performed included flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, microRNA (miR), and gene expression.

The investigators found that, after the reseeding and bioreactor process, an extracellular matrix-like coating and proliferating cells, including a CD105+ subpopulation, were noted in the scaffold. The patient was tumor-free and asymptomatic five months following transplantation, and there were no major complications. Peripheral cells displaying elevated mesenchymal stromal cell phenotype were mobilized, and epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers were upregulated postoperatively.

"The successful overall clinical outcome of this first-in-man bioengineered artificial tracheobronchial transplantation provides ongoing proof of the viability of this approach, in which a cell-seeded synthetic graft is fabricated to patient-specific anatomical requirements and incubated to maturity within the environment of a bioreactor," the authors write.

The study was partially funded by University College London Business and StratRegen.

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