Short‐Term Preclinical Application of Functional Human Induced Pluripotent Stem Cell‐Derived Airway Epithelial Patches

Varma, Ratna; Marin-Araujo, Alba E; Rostami, Shahrbano; Waddell, Thomas K.; Karoubi, Golnaz; Haykal, Siba

doi:10.1002/adhm.202100957

Cited by 7 publications

(4 citation statements)

References 93 publications

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“…Because ciliated and basal cells were also observed in samples with low survival rates of hiPSC-AECs, these cells have a high ability to survive post-transplantation. As hiPSC-AECs transplanted with a high proportion of ciliated cells show high survival rates post-transplantation 32 , the area containing ciliated cells could preferentially remain in transplanted AECs. Basal cells have high resistance to drug-related injury compared with other cell types 33 .…”

Section: Discussionmentioning

confidence: 99%

Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation

Kitano,

Hayashi,

Ohnishi

et al. 2024

Cell Transplant

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No radical treatment is available for the regeneration of dysfunction and defects in airway epithelia. Artificial tracheae made of polypropylene and collagen sponge were used in clinical studies to reconstitute tracheae after resection. For early epithelialization of the luminal surface of the artificial trachea, a model was established, that is, an artificial trachea covered with human-induced pluripotent stem cell-derived airway epithelial cells (hiPSC-AECs) was transplanted into a tracheal defect in an immunodeficient rat. Unlike the cell types of hiPSC-derived cells that are currently used in clinical studies, AECs maintain tissues by proliferation and differentiation of basal cells into various cell types that constitute AECs constantly. Therefore, post-transplantation, the proportion of each cell type, such as ciliated and goblet cells, may change; however, no studies have examined this possibility. In this study, using our hiPSC-AEC-transplanted rat model, we investigated changes in the proportion of each cell type in hiPSC-AECs pre-transplantation and post-transplantation. As a result, the proportion of each cell type changed post-transplantation. The proportion of ciliated, basal, and club cells increased, and the proportion of goblet cells decreased post-transplantation. In addition, the proportion of each cell type in engrafted hiPSC-AECs is more similar to the proportion of each cell type in normal proximal airway tissue than the proportion of each cell type pre-transplantation. The results of this study are useful for the development of therapeutic techniques using hiPSC-AEC transplantation.

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Section: Discussionmentioning

confidence: 99%

Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation

Kitano,

Hayashi,

Ohnishi

et al. 2024

Cell Transplant

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“…1 ) for an anterior wall defect. The detailed protocol of the surgery has been described previously 23 . Briefly, pigs were anesthetized using an intramuscular (i.m.)…”

Section: Methodsmentioning

confidence: 99%

“…To test various decellularized materials and their ability for long-term tissue integration, a tracheal patch implant model was used and has been shown to be promising 18 , 22 . This approach has been used to evaluate regenerated airway grafts with pluripotent stem cells 23 . This model serves as the initial step to testing the long-term integration and strength of decellularized products.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a decellularized bronchial patch transplant in a porcine model

Taniguchi,

Kamata,

Rostami

et al. 2023

Sci Rep

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Biological scaffolds for airway reconstruction are an important clinical need and have been extensively investigated experimentally and clinically, but without uniform success. In this study, we evaluated the use of a decellularized bronchus graft for airway reconstruction. Decellularized left bronchi were procured from decellularized porcine lungs and utilized as grafts for airway patch transplantation. A tracheal window was created and the decellularized bronchus was transplanted into the defect in a porcine model. Animals were euthanized at 7 days, 1 month, and 2 months post-operatively. Histological analysis, immunohistochemistry, scanning electron microscopy, and strength tests were conducted in order to evaluate epithelialization, inflammation, and physical strength of the graft. All pigs recovered from general anesthesia and survived without airway obstruction until the planned euthanasia timepoint. Histological and electron microscopy analyses revealed that the decellularized bronchus graft was well integrated with native tissue and covered by an epithelial layer at 1 month. Immunostaining of the decellularized bronchus graft was positive for CD31 and no difference was observed with immune markers (CD3, CD11b, myeloperoxidase) at two months. Although not significant, tensile strength was decreased after one month, but recovered by two months. Decellularized bronchial grafts show promising results for airway patch reconstruction in a porcine model. Revascularization and re-epithelialization were observed and the immunological reaction was comparable with the autografts. This approach is clinically relevant and could potentially be utilized for future applications for tracheal replacement.

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“…The involvement of induced Pluripotent stem cells (iPs) offers a fresh perspective on tracheal regeneration. When evaluating ex vivo tracheal repair using human iPs derived silk fibroin collagen vitrigel membrane patches, evidence of mucociliary epithelium maintenance was observed alongside native tracheal epithelial metabolism [53]. Motile cilia were also observed in rats following histological analysis two weeks after the iPs based collagen scaffold was introduced as a tracheal segment [54].…”

Section: Stem-cell Biology and Epithelial Reconstructionmentioning

confidence: 99%

Surgical Innovations in Tracheal Reconstruction: A Review on Synthetic Material Fabrication

Khalid,

Uchikov,

Hristov

et al. 2023

Medicina

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Background and Objectives: The aim of this review is to explore the recent surgical innovations in tracheal reconstruction by evaluating the uses of synthetic material fabrication when dealing with tracheomalacia or stenotic pathologies, then discussing the challenges holding back these innovations. Materials and Methods: A targeted non-systematic review of published literature relating to tracheal reconstruction was performed within the PubMed database to help identify how synthetic materials are utilised to innovate tracheal reconstruction. Results: The advancements in 3D printing to aid synthetic material fabrication have unveiled promising alternatives to conventional approaches. Achieving successful tracheal reconstruction through this technology demands that the 3D models exhibit biocompatibility with neighbouring tracheal elements by encompassing vasculature, chondral foundation, and immunocompatibility. Tracheal reconstruction has employed grafts and scaffolds, showing a promising beginning in vivo. Concurrently, the integration of resorbable models and stem cell therapy serves to underscore their viability and application in the context of tracheal pathologies. Despite this, certain barriers hinder its advancement in surgery. The intricate tracheal structure has posed a challenge for researchers seeking novel approaches to support its growth and regeneration. Conclusions: The potential of synthetic material fabrication has shown promising outcomes in initial studies involving smaller animals. Yet, to fully realise the applicability of these innovative developments, research must progress toward clinical trials. These trials would ascertain the anatomical and physiological effects on the human body, enabling a thorough evaluation of post-operative outcomes and any potential complications linked to the materials or cells implanted in the trachea.

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Short‐Term Preclinical Application of Functional Human Induced Pluripotent Stem Cell‐Derived Airway Epithelial Patches

Cited by 7 publications

References 93 publications

Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation

Changes in the Proportion of Each Cell Type After hiPSC-Derived Airway Epithelia Transplantation

Evaluation of a decellularized bronchial patch transplant in a porcine model

Surgical Innovations in Tracheal Reconstruction: A Review on Synthetic Material Fabrication

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