Reference - Detail
| RRC ID | 68394 |
|---|---|
| Author | Takahashi H, Nakashima T, Masuda T, Namba M, Sakamoto S, Yamaguchi K, Horimasu Y, Miyamoto S, Iwamoto H, Fujitaka K, Hamada H, Hattori N. |
| Title | Antifibrotic effect of lung-resident progenitor cells with high aldehyde dehydrogenase activity. |
| Journal | Stem Cell Res Ther |
| Abstract |
BACKGROUND:Aldehyde dehydrogenase (ALDH) is highly expressed in stem/progenitor cells in various tissues, and cell populations with high ALDH activity (ALDHbr) are associated with tissue repair. However, little is known about lung-resident ALDHbr. This study was performed to clarify the characteristics of lung-resident ALDHbr cells and to evaluate their possible use as a tool for cell therapy using a mouse model of bleomycin-induced pulmonary fibrosis. METHODS:The characteristics of lung-resident/nonhematopoietic (CD45-) ALDHbr cells were assessed in control C57BL/6 mice. The kinetics and the potential usage of CD45-/ALDHbr for cell therapy were investigated in bleomycin-induced pulmonary fibrosis. Localization of transferred CD45-/ALDHbr cells was determined using mCherry-expressing mice as donors. The effects of aging on ALDH expression were also assessed using aged mice. RESULTS:Lung CD45-/ALDHbr showed higher proliferative and colony-forming potential than cell populations with low ALDH activity. The CD45-/ALDHbr cell population, and especially its CD45-/ALDHbr/PDGFRα+ subpopulation, was significantly reduced in the lung during bleomycin-induced pulmonary fibrosis. Furthermore, mRNA expression of ALDH isoforms was significantly reduced in the fibrotic lung. When transferred in vivo into bleomycin-pretreated mice, CD45-/ALDHbr cells reached the site of injury, ameliorated pulmonary fibrosis, recovered the reduced expression of ALDH mRNA, and prolonged survival, which was associated with the upregulation of the retinol-metabolizing pathway and the suppression of profibrotic cytokines. The reduction in CD45-/ALDHbr/PDGFRα+ population was more remarkable in aged mice than in young mice. CONCLUSIONS:Our results strongly suggest that the lung expression of ALDH and lung-resident CD45-/ALDHbr cells are involved in pulmonary fibrosis. The current study signified the possibility that CD45-/ALDHbr cells could find application as novel and useful cell therapy tools in pulmonary fibrosis treatment. |
| Volume | 12(1) |
| Pages | 471 |
| Published | 2021-8-23 |
| DOI | 10.1186/s13287-021-02549-6 |
| PII | 10.1186/s13287-021-02549-6 |
| PMID | 34425896 |
| PMC | PMC8381511 |
| MeSH | Aldehyde Dehydrogenase Animals Bleomycin / toxicity Lung Mice Mice, Inbred C57BL Pulmonary Fibrosis* / chemically induced Pulmonary Fibrosis* / therapy Stem Cells* |
| IF | 5.116 |
| Resource | |
| Mice | C57BL/6-Gt(ROSA)26Sor |