Therapeutic Efficacy of Human Mesenchymal Stromal Cells in the Repair of Established Ventilator-induced Lung Injury in the Rat

• Published in: Anesthesiology (Philadelphia) Vol. 122; no. 2; pp. 363 - 373
• Main Authors: Hayes, Mairead, Masterson, Claire, Devaney, James, Barry, Frank, Elliman, Steve, O’Brien, Timothy, O’Toole, Daniel, Curley, Gerard F, Laffey, John G
• Format: Journal Article
• Language: English
• Published: United States American Society of Anesthesiologists, Inc 01.02.2015
• Subjects: Animals; Fibroblasts; Humans; Lung - pathology; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells; Rats; Rats, Sprague-Dawley; Ventilator-Induced Lung Injury - pathology; Ventilator-Induced Lung Injury - therapy
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0000000000000545

BACKGROUND:Rodent mesenchymal stem/stromal cells (MSCs) enhance repair after ventilator-induced lung injury (VILI). We wished to determine the therapeutic potential of human MSCs (hMSCs) in repairing the rodent lung. METHODS:In series 1, anesthetized rats underwent VILI (series 1A, n = 8 to 9 per group) or protective ventilation (series 1B, n = 4 per group). After VILI, they were randomized to intravenous administration of (1) vehicle (phosphate-buffered saline); (2) fibroblasts (1 × 10 cells/kg); or (3) human MSCs (1 × 10 cells/kg) and the effect on restoration of lung function and structure assessed. In series 2, the efficacy of hMSC doses of 1, 2, 5, and 10 million/kg was examined (n = 8 per group). Series 3 compared the efficacy of both intratracheal and intraperitoneal hMSC administration to intravascular delivery (n = 5–10 per group). Series 4 examined the efficacy of delayed hMSC administration (n = 8 per group). RESULTS:Human MSC’s enhanced lung repair, restoring oxygenation (131 ± 19 vs. 103 ± 11 vs. 95 ± 11 mmHg, P = 0.004) compared to vehicle or fibroblast therapy, respectively. hMSCs improved lung compliance, reducing alveolar edema, and restoring lung architecture. hMSCs attenuated lung inflammation, decreasing alveolar cellular infiltration, and decreasing cytokine-induced neutrophil chemoattractant-1 and interleukin-6 while increasing keratinocyte growth factor concentrations. The lowest effective hMSC dose was 2 × 10 hMSC/kg. Intraperitoneal hMSC delivery was less effective than intratracheal or intravenous hMSC. hMSCs enhanced lung repair when administered at later time points after VILI. CONCLUSIONS:hMSC therapy demonstrates therapeutic potential in enhancing recovery after VILI.