Am J Respir Crit Care Med 2023 Oct 05; doi: 10.1164/rccm.202305-0865OC.

Intravenous Autologous Bone-Marrow-derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine.

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OBJECTIVE: Assess efficacy of immediate post-injury intravenous administration of autologous or allogeneic bone-marrow-derived mesenchymal stromal cells (MSCs) for treatment of ARDS due to smoke inhalation and burns. METHODS: Yorkshire swine (n=32, 44.3±0.5 kg), underwent intravenous anesthesia, placement of lines, severe smoke inhalation and 40% total body surface area flame burns, followed by 72 h of round-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung CT scans and arterial blood assays were performed. Following injury and 24 and 48 h later, animals were randomized to receive either autologous concentrated bone-marrow aspirate (n=10; WBC 3x106 and mean platelets 56.6x106 per dose); allogeneic (n=10, 6.1x106 MSCs per dose) harvested from healthy donor swine; or no treatment in injured controls (n=12). MEASUREMENTS AND MAIN RESULTS: Intravenous administration of MSCs after injury and at 24 and 48 h delayed onset of ARDS in autologous (48±10 h) vs. controls (14±2 h, p=0.004); reduced ARDS severity at 24 (p<.001) and 48 h (p= 0.003) and demonstrated visibly less consolidation on CT (n.s.). Mortality at 72 hours was (1/10 (10%) in autologous, 5/10 (50%) in allogeneic, and 6/12 (50%) in INJC (n.s). Both autologous and allogeneic suppressed systemic levels of TNF-α. CONCLUSION: Intravenous administration of 3 doses of freshly processed autologous bone-marrow-derived mesenchymal stromal cells delay ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous mesenchymal stromal cells in swine is feasible and may be viable injury-mitigation strategy for ARDS.

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