Engraftment and proliferation potential of embryonic lung tissue cells in irradiated mice with emphysema

Recently, there has been increasing interest in stem cell transplantation therapy, to treat chronic respiratory diseases, using lung epithelial cells or alveolospheres derived from endogenous lung progenitor cells. However, optimal transplantation strategy of these cells has not been addressed. To g...

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Bibliographic Details
Published in:Scientific reports Vol. 9; no. 1; p. 3657
Main Authors: Shiraishi, Kazushige, Shichino, Shigeyuki, Tsukui, Tatsuya, Hashimoto, Shinichi, Ueha, Satoshi, Matsushima, Kouji
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 06.03.2019
Nature Publishing Group
Subjects:
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13/31
13/51
14/19
38/1
38/39
38/90
38/91
631/532/2117
631/532/489
Cell adhesion
Cell adhesion & migration
Cell cycle
Cell proliferation
Developmental stages
Elastase
Emphysema
Endothelial cells
Epithelial cells
Gene expression
Humanities and Social Sciences
Irradiation
Lung diseases
Lung transplantation
Mesenchyme
multidisciplinary
Progenitor cells
Radiation
Respiratory diseases
Science
Science (multidisciplinary)
Stem cell transplantation
Stem cells
Transcription
Transplantation
Trinucleotide repeats
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Recently, there has been increasing interest in stem cell transplantation therapy, to treat chronic respiratory diseases, using lung epithelial cells or alveolospheres derived from endogenous lung progenitor cells. However, optimal transplantation strategy of these cells has not been addressed. To gain insight into the optimization of stem cell transplantation therapy, we investigated whether lung cell engraftment potential differ among different developmental stages. After preconditioning with irradiation and elastase to induce lung damage, we infused embryonic day 15.5 (E15.5) CAG-EGFP whole lung cells, and confirmed the engraftment of epithelial cells, endothelial cells, and mesenchymal cells. The number of EGFP-positive epithelial cells increased from day 7 to 28 after infusion. Among epithelial cells derived from E13.5, E15.5, E18.5, P7, P14, and P56 mice, E15.5 cells demonstrated the most efficient engraftment. In vitro , E15.5 epithelial cells showed high proliferation potential. Transcriptome analyses of sorted epithelial cells from E13.5, E15.5, E18.5, P14, and P56 mice revealed that cell cycle and cell-cell adhesion genes were highly enriched in E15.5 epithelial cells. Our findings suggest that cell therapy for lung diseases might be most effective when epithelial cells with transcriptional traits similar to those of E15.5 epithelial cells are used.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-40237-x