Antifibrotic effect of lung-resident progenitor cells with high aldehyde dehydrogenase activity

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.

Modeling of Aberrant Epithelial Reprogramming in Idiopathic Pulmonary Fibrosis using Human Induced Pluripotent Stem Cell-derived Alveolar Organoids

“…1H and List S11), we found LRRK2 which loss is linked to AT2 cell dysfunction in experimental pulmonary fibrosis (44). We also noted ALDH1A1 in this group of genes, which is associated with stemness and exert anti-fibrotic properties when highly expressed in lung epithelial cells in experimental pulmonary fibrosis models in mouse (45). Taken together, these results show that the FC-induced transcriptomic changes share similarities to those seen in IPF.…”

ALDH2 promotes cancer stemness and metastasis in colorectal cancer through activating β‐catenin signaling

“…Previous studies have found that ALDH+ cells have a stemcell characteristic, often making cancer cells more resistant to common chemotherapeutic drugs. 20,23,79 This study has limitations such as dissecting the whole signaling cascade of ALDH2-mediated EMT, stemness modulation and invivo studies.…”

MELTF Might Regulate Ferroptosis, Pyroptosis, and Autophagy in Platelet-Rich Plasma-Mediated Endometrial Epithelium Regeneration

“…The atRA could promote cellular proliferation, differentiation, morphogenesis, cell survival, angiogenesis, wound recovery and stem cell migration mediated by the retinoic acid receptors (RARs) [23,24]. The atRA could inhibit the brosis of lung, liver and rein [25][26][27]. The atRA could also inhibit the endometrial brosis in a rat IUA model [28].…”