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
Mice C57BL/6-Gt(ROSA)26Sor (BRC No. RBRC06036)