Sex-related differences in efficacy of bone marrow-derived high aldehyde dehydrogenase activity cells against pulmonary fibrosis

Autor: Shugo Inada, Taku Nakashima, Takeshi Masuda, Kiyofumi Shimoji, Shinjiro Sakamoto, Kakuhiro Yamaguchi, Yasushi Horimasu, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Stem Cell Research & Therapy, Vol 15, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 1757-6512
DOI: 10.1186/s13287-024-03933-8
Popis: Abstract Background Although bone marrow-derived cells with high aldehyde dehydrogenase activity (ALDHbr) have shown therapeutic potential against various diseases in animal studies, clinical trials have failed to show concurrent findings. We aimed to clarify the optimal conditions for the efficacy of ALDHbr cells by using a murine bleomycin-induced pulmonary fibrosis model. Methods We intravenously transferred male or female donor C57BL/6 mice-derived ALDHbr cells into recipient C57BL/6 mice under various conditions, and used mCherry-expressing mice as a donor to trace the transferred ALDHbr cells. Results Pulmonary fibrosis improved significantly when (1) female-derived, not male-derived, and (2) lineage (Lin)-negative, not lineage-positive, ALDHbr cells were transferred during the (3) fibrotic, not inflammatory, phase. Consistent with the RNA-sequencing results, female-derived Lin−/ALDHbr cells were more resistant to oxidative stress than male-derived cells in vitro, and transferred female-derived Lin−/ALDHbr cells were more viable than male-derived cells in the fibrotic lung. The mechanism underlying the antifibrotic effects of Lin−/ALDHbr cells was strongly associated with reduction of oxidative stress. Conclusions Our results indicated that Lin−/ALDHbr cell therapy could ameliorate pulmonary fibrosis by reducing oxidative stress and suggested that their efficacy was mediated by sex-related differences. Thus, sex-awareness strategies may be important for clinical application of bone marrow ALDHbr cells as a therapeutic tool.
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje