Therapeutic Efficacy of Co-administered WJ-MSCs and Exosomes in a Rat Pulmonary Fibrosis Model.

BACKGROUND/AIM: Pulmonary fibrosis lacks therapies capable of reversing established fibrosis. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) show anti-fibrotic promise but are limited by poor engraftment in the fibrotic microenvironment. Evidence from tissue repair models suggests co-delivery of MSC-derived exosomes improves MSC engraftment. Whether WJ-MSCs and their own exosomes produce complementary anti-fibrotic effects in pulmonary fibrosis remains unknown. This study preliminarily evaluated this hypothesis in vivo. MATERIALS AND METHODS: Pulmonary fibrosis was induced in left lungs of male rats using bleomycin. At 21 days after bleomycin injection, animals were assigned to WJ-MSC monotherapy, exosome monotherapy, or combination therapy. At 49 days, these treatment groups, alongside normal and bleomycin-treated controls, were evaluated via gross morphological assessment, lung weight measurement, and histological analysis using Masson's trichrome staining to quantify the fibrotic area. RESULTS: Histological evaluation demonstrated significant fibrotic area expansion in the bleomycin group. While WJ-MSC or exosome monotherapies yielded minimal reduction in fibrotic burden, the combination therapy attenuated the fibrotic area by approximately 50% relative to the bleomycin-treated control, accompanied by a notable restoration of alveolar architecture. CONCLUSION: Co-administration of WJ-MSCs and their derived exosomes produced substantially greater anti-fibrotic effects than either treatment alone. These preliminary findings suggest exosomes prime the fibrotic microenvironment to enhance WJ-MSC engraftment, with additive paracrine contributions driving superior efficacy. As a single fixed dose at the upper range of previously validated doses was used due to limited animal numbers, future studies with dose-response designs, molecular marker analysis, and functional assessments are warranted.