Autologous Cell Seeding in Tracheal Tissue Engineering

Current Stem Cell Reports, Oct 2017

Purpose of Review There is no consensus on the best technology to be employed for tracheal replacement. One particularly promising approach is based upon tissue engineering and involves applying autologous cells to transplantable scaffolds. Here, we present the reported pre-clinical and clinical data exploring the various options for achieving such seeding. Recent Findings Various cell combinations, delivery strategies, and outcome measures are described. Mesenchymal stem cells (MSCs) are the most widely employed cell type in tracheal bioengineering. Airway epithelial cell luminal seeding is also widely employed, alone or in combination with other cell types. Combinations have thus far shown the greatest promise. Chondrocytes may improve mechanical outcomes in pre-clinical models, but have not been clinically tested. Rapid or pre-vascularization of scaffolds is an important consideration. Overall, there are few published objective measures of post-seeding cell viability, survival, or overall efficacy. Summary There is no clear consensus on the optimal cell-scaffold combination and mechanisms for seeding. Systematic in vivo work is required to assess differences between tracheal grafts seeded with combinations of clinically deliverable cell types using objective outcome measures, including those for functionality and host immune response.

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Autologous Cell Seeding in Tracheal Tissue Engineering

Autologous Cell Seeding in Tracheal Tissue Engineering Elizabeth F. Maughan 0 1 2 4 5 Robert E. Hynds 0 1 2 4 5 Toby J. Proctor 0 1 2 4 5 Sam M. Janes 0 1 2 4 5 Martin Elliott 0 1 2 4 5 Martin A. Birchall 0 1 2 4 5 Mark W. Lowdell 0 1 2 4 5 Paolo De Coppi 0 1 2 4 5 0 Centre for Cell, Gene and Tissue Therapies, Royal Free Hospital & University College London , London , UK 1 Stem Cell and Regenerative Medicine Section, UCL Institute of Child Health and Great Ormond Street Hospital , 30 Guilford Street, London WC1N 1EH , UK 2 Lungs for Living Research Centre, UCL Respiratory, University College London , London , UK 3 Paolo De Coppi 4 UCL Centre for Regenerative Medicine, University College London , London , UK 5 Great Ormond Street Hospital , London , UK Purpose of Review There is no consensus on the best technology to be employed for tracheal replacement. One particularly promising approach is based upon tissue engineering and involves applying autologous cells to transplantable scaffolds. Here, we present the reported pre-clinical and clinical data exploring the various options for achieving such seeding. Recent Findings Various cell combinations, delivery strategies, and outcome measures are described. Mesenchymal stem cells (MSCs) are the most widely employed cell type in tracheal bioengineering. Airway epithelial cell luminal seeding is also widely employed, alone or in combination with other cell types. Combinations have thus far shown the greatest promise. Chondrocytes may improve mechanical outcomes in pre-clinical models, but have not been clinically tested. Rapid or pre-vascularization of scaffolds is an important consideration. Overall, there are few published objective measures of post-seeding cell viability, survival, or overall efficacy. Summary There is no clear consensus on the optimal cellscaffold combination and mechanisms for seeding. Systematic in vivo work is required to assess differences between tracheal grafts seeded with combinations of clinically deliverable cell types using objective outcome measures, including those for functionality and host immune response. Trachea; Tissue engineering; Autologous cell seeding; Pre-clinical models; Clinical translation Introduction Treatment outcomes for long-segment tracheal disease in children have been steadily improving over the last decade, due mostly to advances in the slide tracheoplasty technique and improvements in post-operative care [ 1 ]. However, there remains a small subset of patients with extensive disease who cannot be managed by conventional means, as surgical resection would lead to an unacceptable level of tension on the anastomotic joins and failure of ventilation from kinking of the carina [ 2 ]. Endoscopic or conventional open surgery, such as end-to-end resection, can manage the majority of adult patients with acquired or idiopathic tracheal stenosis [ 3, 4 ]. These patients are those whose tracheal disease exceeds 50% of the total tracheal length in adults (or 30% of the total length in children) [ 5, 6 ], those whose primary reconstruction is unsuccessful, or those whose underlying tracheal disease recurs. In adults, voice outcomes from resection surgery are often suboptimal and recurrent stenosis is common [ 7 ]. In these, sometimes life-threatening and life-changing, circumstances, part- or whole-organ scale replacement of the trachea could be life-transforming or life-saving. Interest in the field of regenerative medicine has grown exponentially in recent decades, and the subfield of tissue engineering sits at the intersection between cell biology, materials science, and engineering. In contrast to passive implants and medical constructs that are already widely employed across human and veterinary medicine, tissueengineered medical devices aim to functionally repair, replace, or regenerate living tissue [ 8, 9 ]. The basic principle behind tissue engineering is to manufacture a biocompatible scaffold that supports the growth and differentiation of the recipient’s cells, to create a functioning neo-organ upon implantation [10]. Personalized scaffolds created in this way should not evoke conventional immune rejection responses and can thus be implanted without the need for immunosuppressive medication. In children, functional regeneration and remodeling of the replaced tissue might obviate the risk of the child outgrowing the transplant and needing serial re-transplantation. The trachea was initially considered, perhaps naively, to be a convenient Bstarter organ^ on which to concentrate tissue engineering efforts, due to its relatively simple tubular anatomy and Bbasic^ primary function of passive air conduction to the lungs [ 11 ]. Given the lack of alternative treatment options in end-stage (often emergent) tracheal disease, the use of experimental therapies raises fewer potential ethical objections than in other clinical areas [ 12 ]. Regenerative approaches to tracheal reconstruction have, ther (...truncated)


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Elizabeth F. Maughan, Robert E. Hynds, Toby J. Proctor, Sam M. Janes, Martin Elliott, Martin A. Birchall, Mark W. Lowdell, Paolo De Coppi. Autologous Cell Seeding in Tracheal Tissue Engineering, Current Stem Cell Reports, 2017, pp. 1-11, DOI: 10.1007/s40778-017-0108-2