Clinical Application of in Situ Tissue Engineering Using a Scaffolding Technique for Reconstruction of the Larynx and Trachea

Omori, Koichi; Tada, Yasuhiro; Suzuki, Teruhisa; Nomoto, Yukio; Matsuzuka, Takashi; Kobayashi, Ken; Nakamura, Tatsuo; Kanemaru, Shin‐ichi; Yamashita, Masaru; Asato, Ryo

doi:10.1177/000348940811700908

Cited by 144 publications

(100 citation statements)

References 13 publications

(21 reference statements)

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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%

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%

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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“…These induced pluripotent stem (iPS) cells present an important advantage over "real" embryonic stem cells, in that they do not require an embryo to be sacrificed, and that they ultimately will allow autologous transplantation of stem cells to repair damaged tissues (Park et al, 2008). The reprogramming process requires retroviral transduction with at least three genes: Oct3/4, Sox2 and Klf4 (Geoghegan and Byrnes, 2008;Hong et al, 2009), and may require suppression of the tumor suppressor genes p53 and p21 (Hong et al, 2009).…”

Section: Gm Roomansmentioning

confidence: 99%

“…Such a condition is, as stated above, a prime example where repair of the airway by stem cells could be used. Omori et al (2008) developed a tissue scaffold made from a mesh tube covered by collagen sponge, which was implanted to repair the larynx and trachea in 4 patients (1 with subglottic stenosis and 3 with thyroid cancer), where the cartilage of the cervical trachea and laryngeal cartilages were resected and reconstructed by use of the scaffold. This was reported to result in a well-epithelialized airway lumen without any obstruction.…”

Section: Gm Roomansmentioning

confidence: 99%

Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

Roomans

2010

eCM

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Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a) a ductal cell type in the submucosal glands of the proximal trachea, (b) basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c) variant Clara cells (Clara v -cells) in the bronchioles and (d) at the junctions between the bronchioles and the alveolar ducts, and (e) alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a) embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, or amniotic fluid stem cells, (b) side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c) fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

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“…94 This technology of employing decellularized organ scaffolds is advantageous as the native three-dimensional (3D) tissue architecture, vascular tree, and ECM-related cues, all with high developmental significance, seem to be well preserved 94,96 in the organ scaffold. A variety of complex modular organs have now been bioengineered, some of which, such as the larynx 97,98 and vagina, 99 have found clinical use. We highly recommend reviews 87,98 including those by Orlando et al…”

Section: The State Of the Artmentioning

confidence: 99%

On the Genealogy of Tissue Engineering and Regenerative Medicine

Kaul

Ventikos

2015

Tissue Engineering Part B: Reviews

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In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed.

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Clinical Application of in Situ Tissue Engineering Using a Scaffolding Technique for Reconstruction of the Larynx and Trachea

Abstract: Our current technique of in situ tissue engineering using a scaffold shows great potential for use in the regeneration of airway defects.

Cited by 144 publications

References 13 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

Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

On the Genealogy of Tissue Engineering and Regenerative Medicine

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