Regenerative Medicine of the Trachea: The First Human Case

Omori, Koichi; Nakamura, Tatsuo; Kanemaru, Shin‐ichi; Asato, Ryo; Yamashita, Masaru; Tanaka, Shinzo; Magrufov, Akhmar; Ito, Juichi; Shimizu, Yasuhiko

doi:10.1177/000348940511400603

Cited by 200 publications

(148 citation statements)

References 14 publications

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“…To this end, allografts and a wide range of biomaterials have been used for replacing tracheal defects. 9,86,87 The general problems associated with these kinds of implants are restenosis, collapse of the airway due to mechanical instability, and the problems associated with the lack of functional epithelium, which leads to infections and also facilitates restenosis. 88 When the implant is not strong enough, airway collapse is the major issue.…”

Section: Epithelium In Clinical Full Organ/multicellular Tissue-enginmentioning

confidence: 99%

“…8 However, a similar coverage has not been demonstrated for regeneration of the trachea. 9 There are two modes of epithelial renewal, 10 that can happen simultaneously, depending on the nature and location of the injury: (1) a constant renewal mode such as in intestine and (2) renewal via activation of semiquiescent cells by dedifferentiation upon injury such as in bladder. Given all these diversities, it is important to develop specific solutions for the formation of the epithelial layer for each target organ and take into account the in vivo characteristics of epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

Vrana

Lavalle²,

Dokmeci³

et al. 2013

Tissue Engineering Part B: Reviews

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Recent advances in the fields of microfabrication, biomaterials, and tissue engineering have provided new opportunities for developing biomimetic and functional tissues with potential applications in disease modeling, drug discovery, and replacing damaged tissues. An intact epithelium plays an indispensable role in the functionality of several organs such as the trachea, esophagus, and cornea. Furthermore, the integrity of the epithelial barrier and its degree of differentiation would define the level of success in tissue engineering of other organs such as the bladder and the skin. In this review, we focus on the challenges and requirements associated with engineering of epithelial layers in different tissues. Functional epithelial layers can be achieved by methods such as cell sheets, cell homing, and in situ epithelialization. However, for organs composed of several tissues, other important factors such as (1) in vivo epithelial cell migration, (2) multicell-type differentiation within the epithelium, and (3) epithelial cell interactions with the underlying mesenchymal cells should also be considered. Recent successful clinical trials in tissue engineering of the trachea have highlighted the importance of a functional epithelium for long-term success and survival of tissue replacements. Hence, using the trachea as a model tissue in clinical use, we describe the optimal structure of an artificial epithelium as well as challenges of obtaining a fully functional epithelium in macroscale. One of the possible remedies to address such challenges is the use of bottom-up fabrication methods to obtain a functional epithelium. Modular approaches for the generation of functional epithelial layers are reviewed and other emerging applications of microscale epithelial tissue models for studying epithelial/mesenchymal interactions in healthy and diseased (e.g., cancer) tissues are described. These models can elucidate the epithelial/mesenchymal tissue interactions at the microscale and provide the necessary tools for the next generation of multicellular engineered tissues and organ-on-a-chip systems.

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Section: Epithelium In Clinical Full Organ/multicellular Tissue-enginmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

Vrana

Lavalle²,

Dokmeci³

et al. 2013

Tissue Engineering Part B: Reviews

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show abstract

“…In 2005, Omori et al 37) constructed a TET to repair the trachea of a 78-year-old woman using a scaffold of Marlex porous mesh tube covered by a collagen sponge made from porcine dermal atelocollagen. The collagen sponge was intended to enhance tissue invasion into the Marlex mesh scaffold and thus, assist in re-epithelialization of the lumen.…”

Section: Clinical Application Of Tetmentioning

confidence: 99%

“…37) Thus, a follow-up report was needed. Consequently, the authors of this study reported the 5-year follow-up results.…”

Section: Clinical Application Of Tetmentioning

confidence: 99%

Current Solutions for Long-Segment Tracheal Reconstruction

Abouarab

Elsayed

Elkhayat

et al. 2017

ATCS

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This article is a continuation of previous reviews about the appropriate method for long-segment tracheal reconstruction. We attempted to cover the most recent, successful and promising results of the different solutions for reconstruction that are rather innovative and suitable for imminent clinical application. Latest efforts to minimize the limitations associated with each method have been covered as well. In summary, autologous and allogenic tissue reconstruction of the trachea have been successful methods for reconstruction experimentally and clinically. Autologous tissues were best utilized clinically to enhance revascularization, whether as a definitive airway or as an adjunct to allografts or tissue-engineered trachea (TET). Allogenic tissue transplantation is, currently, the most suitable for clinical application, especially after elimination of the need for immunosuppressive therapy with unlimited supply of tissues. Similar results have been reported in many studies that used TET. However, clinical application of this method was limited to use as a salvage treatment in a few studies with promising results. These results still need to be solidified by further clinical and longterm follow-up reports. Combining different methods of reconstruction was often required to establish a physiological rather than an anatomical trachea and have shown superior outcomes.

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“…Common to many is a foundation built upon a decellularized tracheal allograft 7,8 or a synthetic polymer/nanofiber scaffold. 9 In at least one case, an aortic allograft was employed as the tubular scaffold 10 to provide similar structural support. These scaffolds are then seeded with various cell types to provide functionality, as the size of these grafts limits the degree to which cellular invasion can occur.…”

Section: Introductionmentioning

confidence: 99%

Decellularized Tracheal Extracellular Matrix Supports Epithelial Migration, Differentiation, and Function

Kutten

McGovern

Hobson

et al. 2015

Tissue Engineering Part A

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Tracheal loss is a source of significant morbidity for affected patients with no acceptable solution. Interest in engineering tracheal transplants has created a demand for small animal models of orthotopic tracheal transplantation. Here, we examine the use of a decellularized graft in a murine model of tracheal replacement. Fresh or decellularized tracheas harvested from age-matched female donor C57BL/6 mice were transplanted into syngeneic recipients. Tracheas were decellularized using repeated washes of water, 3% Triton X-100, and 3 M NaCl under cyclic pressure changes, followed by disinfection with 0.1% peracetic acid/4% ethanol, and terminal sterilization by gamma irradiation. Tracheas were explanted for immunolabeling at 1, 4, and 8 weeks following surgery. Video microscopy and computed tomography were performed to assess function and structure. Decellularized grafts supported complete reepithelialization by 8 weeks and motile cilia were observed. Cartilaginous portions of the trachea were maintained in mice receiving fresh transplants, but repopulation of the cartilage was not seen in mice receiving decellularized transplants. We observed superior postsurgical survival, weight gain, and ciliary function in mice receiving fresh transplants compared with those receiving decellularized transplants. The murine orthotopic tracheal transplant provides an appropriate model to assess the repopulation and functional regeneration of decellularized tracheal grafts.

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Regenerative Medicine of the Trachea: The First Human Case

Cited by 200 publications

References 14 publications

Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

Engineering Functional Epithelium for Regenerative Medicine and In Vitro Organ Models: A Review

Current Solutions for Long-Segment Tracheal Reconstruction

Decellularized Tracheal Extracellular Matrix Supports Epithelial Migration, Differentiation, and Function

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