Implantation of Induced Pluripotent Stem Cell–Derived Tracheal Epithelial Cells

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Nakamura, Ryosuke; Otsuki, Koji; Murono, Shigeyuki; Omori, Koichi

doi:10.1177/0003489417713504

Cited by 12 publications

(10 citation statements)

References 25 publications

(27 reference statements)

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“…Therefore, iPSC‐derived cells are an ideal cell source in tracheal regenerative medicine. In our previous studies, embryoid bodies, including ciliated epithelium derived from mouse iPSCs, were transplanted to tracheal defects of nude rats with artificial trachea (Ikeda et al, ). Although ciliated epithelial structures were confirmed, their attributes were not similar to those of endotracheal epithelium, but appeared as cystic tissue under the epithelium, indicating that transplanted epithelial cells need to engraft at the appropriate site and that there is a need to improve the induction efficiency by minimizing the inclusion of other cell types during transplant.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of multiciliated airway cells derived from human iPS cells using an artificial tracheal patch into rat trachea

Okuyama

Ohnishi

Nakamura

et al. 2019

J Tissue Eng Regen Med

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Tracheal resection is often performed for malignant tumours, congenital anomalies, inflammatory lesions, and traumatic injuries. There is no consensus on the best approach for the restoration of tracheal functionality in patients with tracheal defects. Artificial grafts made of polypropylene and collagen sponge have been clinically used by our group. However, 2 months are required to achieve adequate epithelialization of the grafts in humans. This study aimed to investigate the feasibility of transplantation therapy using an artificial trachea with human‐induced pluripotent stem cell (hiPSC)‐derived multiciliated airway cells (hiPSC‐MCACs). Collagen vitrigel membrane, a biocompatible and absorbable material, was used as a scaffold to cover the artificial trachea with hiPSC‐MCACs. Analyses of hiPSC‐MCACs on collagen vitrigel membrane were performed by immunocytochemistry and electron microscopy and by assessing ciliary beat frequency. Along with the artificial trachea, hiPSC‐MCACs were transplanted into surgically created tracheal defects of immunodeficient rats. The survival of transplanted cells was histologically evaluated at 1 and 2 weeks after the transplantation. The hiPSC‐MCACs exhibited motile cilia on collagen vitrigel membrane. The surviving hiPSC‐MCACs were observed in the endotracheal epithelium of the tracheal defect at 1 and 2 weeks after transplantation. These results suggest that hiPSC‐MCAC is a useful candidate for tracheal reconstruction.

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Section: Introductionmentioning

confidence: 99%

Transplantation of multiciliated airway cells derived from human iPS cells using an artificial tracheal patch into rat trachea

Okuyama

Ohnishi

Nakamura

et al. 2019

J Tissue Eng Regen Med

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“…Although ciliary beat frequency analysis has revealed that the restoration of normal cilia motility is achieved by a cell-free scaffold, the direction of ciliary movement remains to be investigated [ 21 ]. Scaffold coated with cultured ciliated epithelium is one option [ 24 ], but it is desirable for the epithelial cells to acquire coordinated PCP in culture before transplantation, or to adjust PCP after transplantation.…”

Section: Introductionmentioning

confidence: 99%

Long-term preservation of planar cell polarity in reversed tracheal epithelium

et al. 2018

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BackgroundPlanar cell polarity (PCP) coordinates the patterning and orientation of cells and their structures along tissue planes, and although its acquisition during the formation of airway epithelium has been described, the mechanisms for its maintenance and reconstruction are poorly understood. We aimed to clarify whether ambient environment change by orthotropic autologous transplantation affected PCP at the cellular level.MethodsWe performed orthotropic autologous transplantation by inverting tracheal segments in rats, and then performed morphological evaluation by microscopy. The PCP of the tracheal epithelium was assessed over time by analyzing the directions of mucociliary transport and ciliary beat, the positional relationship between the basal body and basal foot, and the bias of Vang-like protein 1 (Vangl1) at 2, 4, and 6 months postoperatively.ResultsAfter 2 months, the directions of mucociliary transport and ciliary beat were preserved toward the lung in the inverted tracheal segments. The positional relationship between the basal body and the basal foot, and the bias of Vangl1, also indicated preservation of PCP in the inverted tracheal segments. Similar results were obtained at 6 months.ConclusionThe PCP of ciliated epithelium was preserved in reversed trachea, even after long-term observation.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0726-y) contains supplementary material, which is available to authorized users.

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“…Several reports have demonstrated that epithelial regeneration is enhanced by various cells and bioactive molecules, such as growth factors and cytokines 13,27 . Each of these factors has distinct effects on re-epithelialization.…”

Section: Discussionmentioning

confidence: 99%

“…However, despite the advantages of bioactive scaffolds, mucosal regeneration on the internal surface of the scaffold cannot maintain the patent airway without tracheal cartilage regeneration. Several studies have demonstrated the effects of tracheal tissue engineering, including approaches based on bioreactor systems and stem cell therapy 13,14 . To our knowledge, few researchers have successfully induced tracheal cartilage into segmental tracheal defects.…”

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Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes

Kim

Park

Lee

et al. 2020

Sci Rep

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For successful tracheal reconstruction, tissue-engineered artificial trachea should meet several requirements, such as biocompatible constructs comparable to natural trachea, coverage with ciliated respiratory mucosa, and adequate cartilage remodeling to support a cylindrical structure. Here, we designed an artificial trachea with mechanical properties similar to the native trachea that can enhance the regeneration of tracheal mucosa and cartilage through the optimal combination of a two-layered tubular scaffold and human induced pluripotent stem cell (iPSC)-derived cells. The framework of the artificial trachea was fabricated with electrospun polycaprolactone (PCL) nanofibers (inner) and 3D-printed PCL microfibers (outer). Also, human bronchial epithelial cells (hBECs), iPSCderived mesenchymal stem cells (iPSC-MSCs), and iPSC-derived chondrocytes (iPSC-Chds) were used to maximize the regeneration of tracheal mucosa and cartilage in vivo. After 2 days of cultivation using a bioreactor system, tissue-engineered artificial tracheas were transplanted into a segmental trachea defect (1.5-cm length) rabbit model. Endoscopy did not reveal granulation ingrowth into tracheal lumen. Alcian blue staining clearly showed the formation of ciliated columnar epithelium in iPSC-MSC groups. In addition, micro-CT analysis showed that iPSC-Chd groups were effective in forming neocartilage at defect sites. Therefore, this study describes a promising approach for long-term functional reconstruction of a segmental tracheal defect.

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Implantation of Induced Pluripotent Stem Cell–Derived Tracheal Epithelial Cells

Abstract: After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

Cited by 12 publications

References 25 publications

Transplantation of multiciliated airway cells derived from human iPS cells using an artificial tracheal patch into rat trachea

Transplantation of multiciliated airway cells derived from human iPS cells using an artificial tracheal patch into rat trachea

Long-term preservation of planar cell polarity in reversed tracheal epithelium

Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes

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