Study Results

Background

The Larsson lab has the only murine model allowing long-term (weeks, months) studies in an immobilized and mechanically ventilated rat.  This model has been used for more than two decades in the study of VIDD and CIM in parallel with clinical studies, allowing for a rich data set against which to assess our novel treatment’s effectiveness.

Hypothesis

Ventilator-induced lung injury (VILI) releases systemic inflammatory and cytotoxic factors affecting organs like the diaphragm. Reducing lung injury is expected to restore diaphragm muscle function.  Bone marrow-derived mesenchymal stem cells (BM-MSCs) produce extracellular vesicles (EVs) that activate repair pathways and modulate immune responses, addressing inflammation and tissue remodeling. Systemic administration of BM-MSC-derived EVs may therefore combat VILI and its role in ventilator-induced diaphragm dysfunction (VIDD).

Evidence

Unpublished studies by Professor Larsson et al. support this hypothesis:

• Rats ventilated for 5–8 days showed significant lung histopathology versus controls.
• Bronchoalveolar lavage (BAL) fluid from injured lungs showed elevated MMP9 and Anxa¹ (inflammation, apoptosis); additional proteins (Anxa1, Anxa2, Hspa5, Myh9, Pigr, Psap, Ubb) were enriched in lung/bronchial cells and linked to inflammation.
• Human BM-MSC-derived EVs reduced lung injury and restored diaphragm muscle fiber size and specific force in rats after 5 days of ventilation, confirmed via blinded evaluation by Prof. Ikeno (UTHSCSA).
• Lung tissue proteomic/metabolomic analyses and BAL fluid proteomics showed restorative effects of EV treatment.
• Diaphragm RNAseq showed functional recovery with EV treatment.
• Single-cell RNAseq indicated increased growth in both Type I and II diaphragm fibers and reduced inflammation via satellite cell activation.
• Diaphragm metabolomics further confirmed restoration following EV treatment.

A list of relevant publications is available here.