Promising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanismsopen accessPromising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms
- Other Titles
- Promising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms
- Authors
- Lee Hanna; Jeong Ok-Yi; Park Hee Jin; Lee Sung-Lim; Bok Eun-yeong; 김민교; Suh Young Sun; Cheon Yun-Hong; Kim Hyun-Ok; Kim Suhee; Chun Sung Hak; Park Jung Min; Lee Young Jin; 이상일
- Issue Date
- Dec-2023
- Publisher
- 대한면역학회
- Keywords
- Interstitial lung disease; Mesenchymal stem cell; Immunomodulation; Apoptosis; Mitochondria
- Citation
- Immune Network, v.23, no.6, pp 1 - 22
- Pages
- 22
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- Immune Network
- Volume
- 23
- Number
- 6
- Start Page
- 1
- End Page
- 22
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/69372
- DOI
- 10.4110/in.2023.23.e45
- ISSN
- 1598-2629
2092-6685
- Abstract
- Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DW-MSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.
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