Both epithelial cells and mesenchymal stem cell–derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs

Go, Tetsuhiko; Jungebluth, Philipp; Baiguero, Silvia; Asnaghi, M. Adelaide; Martorell, Jaume; Ostertag, Helmut; Mantero, Sara; Birchall, Martin A.; Bader, Augustinus; Macchiarini, Paolo

doi:10.1016/j.jtcvs.2009.10.002

Cited by 139 publications

(133 citation statements)

References 15 publications

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“…A number of preclinical studies have indicated re‐epithelialization occurs from migration of cells from the wound edge following tracheal transplantation 14, 15, tracheal replacement with aortic grafts 16, 17 or synthetic material 18. While this might question the need for re‐epithelizing grafts prior to transplantation, evidence exists supporting the role of epithelium in reducing postoperative stenosis and it is probable that transplanted epithelia act as a biological dressing as re‐epithelization occurs from the wound edge 19.…”

Section: Discussionmentioning

confidence: 99%

Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study

Hamilton

Kanani

Roebuck

et al. 2015

American Journal of Transplantation

158

143

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In 2010, a tissue‐engineered trachea was transplanted into a 10‐year‐old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti‐HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross‐sectional area analysis showed restriction of growth within an area of in‐stent stenosis. This report demonstrates the long‐term viability of a decellularized tissue‐engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.

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Section: Discussionmentioning

confidence: 99%

Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study

Hamilton

Kanani

Roebuck

et al. 2015

American Journal of Transplantation

158

143

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“…Recent animal studies showed that seeding with bone marrow derived cells or progenitor cells may contribute to airway tissue regeneration and may also avoid from bacterial contamination [15][16][17]. Use of pluripotent cells like embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is controversial.…”

Section: Cellsmentioning

confidence: 99%

Current status of tracheal tissue engineering

Kumbasar¹,

Uysal²

2017

Curr Thorac Surg

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Management of large airway defects is challenging for clinicians due to lack of effective treatment modalities and eventually interest has turned to the field of airway tissue engineering. Considerable progress has been made within the field of airway tissue engineering in recent years and herein we review these recent advances within this field as applied to regeneration and/or replacement of the trachea. Although there are many encouraging researches, we are still far from any routine clinical application of tissue engineered tracheal grafts and it is essential to perform further experimental and clinical researches in order to improve current results and to broaden the clinical application of airway tissue engineering.

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“…Decellularized aortic grafts [147], jejunum [148,149,150], bladder [151], and trachea [151,152,153,146] …”

Section: Decellularized Tissuementioning

confidence: 99%

“…However, this biomimetic seeding strategy has had some success in humans, when seeding chondrocytes differentiated from MSCs on the exterior surface and epithelial cells on the interior surface [146]. Other combinations of cells utilized for trachea repair are epithelial cells and fibroblasts [172], endothelial cells and epithelial cells [173], chondrocytes and fibroblasts [136], fibroblasts and muscle cells [148], and bone marrow stromal cell-derived chondrocytes and epithelial cells [152,146]. Walles et al evaluated an even greater number of cell types; seeding chondrocytes, bone marrow-derived smooth muscle cells, bone marrowderived endothelial cells, or respiratory epithelium on a decellularized matrix [150].…”

Section: Multiple Cell Typesmentioning

confidence: 99%

“…Heterotopic grafts are useful for verification of biological and immunologic compatibility, however, their predictive ability for orthotopic implantation is limited. Other studies have employed orthotopic implantation, but have tested only a single experimental group, often controlling for in vitro cell seeding rather than processing conditions [151,152,153]. Of those, many were window patches which have increased survival compared to full circumference grafts, but fail to address the underlying clinical need.…”

Section: Acknowledgementsmentioning

confidence: 99%

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