Therapeutic Efficacy of Adipose-Derived Stem Cells for Bleomycin-Induced Idiopathic Pulmonary Fibrosis: A Comparative Study of Intravenous versus Intratracheal Administration
نویسندگان
1 Department of Pediatric, Chung Kang Branch, Cheng Ching Hospital, Taichung, Taiwan
2 Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
3 Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
4 BIONET Therapeutics Corp., Taipei 11497, Taiwan
5 BIONET Therapeutics Corp., Taipei 11497, Taiwan
6 Department of Dermatology, Shiso Municipal Hospital, Hyogo, Japan
7 Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan
8 Department of Pulmonary Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
9 Department of Pulmonary Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
10 Department of Dermatology, The Wilshire Lab and Aesthetic Clinic, Shenzhen, China
doi
10.22074/cellj.2026.2066514.1886چکیده
Objective: To compare the therapeutic effects of intravenous (IV) and intratracheal (IT) delivery of adipose-derived stem cells (ADSCs) in a mouse model of bleomycin (BLM)-induced idiopathic pulmonary fibrosis (IPF).Materials and Methods: In this experimental study, BALB/c mice were divided into 4 groups: control, BLM only, BLM+ADSC(IV), BLM+ADSC(IT). ADSCs were administered on day 14 after BLM induction. Outcomes measured on day 42 included mortality, body weight, lung edema, collagen deposition, fibrosis scoring, cytokine levels (TGF-β, SDF-1, IL-6, IL-1β, TNF-α), hydroxyproline, and leukocyte infiltration.Results: ADSC(IT) reduced mortality more effectively than ADSC(IV). Both IV and IT mitigated weight loss and lung edema with no significant difference. Both routes significantly decreased collagen synthesis, collagen fiber accumulation, Ashcroft scores, and hydroxyproline levels. Both routes lowered TGF-β, α-SMA, TNF-α, IL-6, IL-1β, and SDF-1 levels, and reduced leukocyte infiltration and alveolar barrier dysfunction, with no significant difference between routes.Conclusion: This design enables discrimination between route-dependent and route-independent therapeutic effects of ADSCs, thereby providing new insight into the optimization of stem cell delivery strategies for pulmonary fibrosis. Importantly, whether the choice of delivery route differentially affects survival and inflammatory resolution, independent of antifibrotic efficacy, remains insufficiently addressed in current preclinical studies.
