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

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.

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.

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.

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.