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Endogenous Lung Stem Cells Increased after Lung Injury

¹ Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan

Correspondence and requests for reprints should be addressed to Hiroshi Kubo, M.D., Ph.D., Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryoumachi, Aobaku, Sendai 980-8574, Japan. E-mail: hkubo{at}mail.tains.tohoku.ac.jp

Previously, we reported that bone marrow–derived cells (BMDCs) play a role in repair processes of the lungs after injury (1, 2). However, long-term BMDC survival in lung parenchyma or their potential for proliferation is not yet clear. In addition, repaired or regenerated alveoli after lung injury are composed of not only BMDCs but also endogenous lung cells, suggesting the role of lung tissue stem cells in the repair processes. Therefore, we investigated the changes in the endogenous lung stem cells in three lung injury models induced by endotoxin, radiation, or elastase in mice. To identify BMDCs, we used GFP-chimera mice, whose bone marrow was replaced with that from GFP-transgenic mice. After lung injury, bone marrow–derived alveolar epithelial cells gradually decreased from the alveolar wall, and did not proliferate to provide new alveolar cells for long periods. The endogenous stem cell population (Sca-1⁺/CD45^–/PECAM^–/GFP^–) increased in the late phase of the injuries (7 d after endotoxin administration or radiation, 3 wk after the elastase administration). Hepatocyte growth factor (HGF) is a potent modulator of epithelial proliferation and migration, and contributes to the repair processes after lung injury. HGF administration dramatically decreases these stem cell populations, suggesting that HGF induces the stem cell differentiation toward mature lung cells and accelerates repair processes. These data suggest that BMDCs do not proliferate to provide new alveolar cells for long periods after lung injury, and BMDCs are not a source of bronchoalveolar stem cell population. The endogenous lung stem cell population increases during the lung injury. We speculate that the difference in the number and function of endogenous stem cell populations affect the resolution of the lung diseases.

FOOTNOTES

Supported by a grant from the Japan Society for the Promotion of Science No 19390222 to H.K.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form August 29, 2007; accepted in final form October 16, 2007)

REFERENCES

1. Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury. J Immunol 2004;172:1266–1272.[Abstract/Free Full Text]
2. Ishizawa K, Kubo H, Yamada M, Kobayashi S, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett 2004;556:249–252.[CrossRef][Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kubo, H. Articles by Yamada, M. Search for Related Content PubMed Articles by Kubo, H. Articles by Yamada, M.