期刊
ANESTHESIOLOGY
卷 122, 期 2, 页码 363-373出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ALN.0000000000000545
关键词
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资金
- European Research Council (Brussels, Belgium) [ERC-2007-StG 207777]
- Health Research Board (Dublin, Ireland) [POR-2011-1061]
- Molecular Medicine Ireland Clinician Scientist Fellowship Award (Molecular Medicine Ireland, funded by the Higher Education Authority, Dublin, Ireland) (HEA PRTLI)
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 x 10(7) cells/kg); or (3) human MSCs (1 x 10(7) 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 x 10(6) 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.
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