From the Regenerative Medicine Institute, National University of Ireland, Galway, Ireland (M.H., C.M., J.D., F.B., T.O., D.O., G.F.C., J.G.L.); Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland (M.H., C.M., J.D., D.O.); Orbsen Therapeutics Ltd, National University of Ireland, Galway, Ireland (S.E; and Department of Anesthesia, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (G.F.C., J.G.L.).
Anesthesiology. 2015 Feb;122(2):363-73. doi: 10.1097/ALN.0000000000000545.
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.
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).
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.
hMSC therapy demonstrates therapeutic potential in enhancing recovery after VILI.
啮齿动物间充质干细胞（MSCs）可增强呼吸机所致肺损伤（VILI）后的修复作用。我们希望确定人 MSCs（hMSCs）在修复啮齿动物肺部方面的治疗潜力。
在系列 1 中，麻醉大鼠接受 VILI（系列 1A，每组 8 至 9 只）或保护性通气（系列 1B，每组 4 只）。VILI 后，它们被随机分为静脉内给予（1）载体（磷酸盐缓冲盐水）；（2）成纤维细胞（1×10 个细胞/kg）；或（3）人 MSCs（1×10 个细胞/kg），并评估其对肺功能和结构恢复的影响。在系列 2 中，检查了 hMSC 剂量为 1、2、5 和 1000 万/kg 的疗效（每组 n = 8）。系列 3 比较了 hMSC 经气管内和腹腔内给药与血管内给药的疗效（每组 n = 5-10）。系列 4 研究了 hMSC 延迟给药的疗效（每组 n = 8）。
与人 MSC 治疗相比，hMSC 增强了肺修复，分别使氧合作用（131 ± 19 对 103 ± 11 对 95 ± 11 mmHg，P = 0.004）得到改善。hMSCs 改善了肺顺应性，减少了肺泡水肿，并恢复了肺结构。hMSC 减轻了肺炎症，减少了肺泡细胞浸润，并降低了细胞因子诱导的中性粒细胞趋化因子-1 和白细胞介素-6 的浓度，同时增加了角质细胞生长因子的浓度。最低有效 hMSC 剂量为 2×10 hMSC/kg。腹腔内 hMSC 给药不如气管内或静脉内 hMSC 给药有效。hMSC 在 VILI 后较晚时间点给药时可增强肺修复作用。
hMSC 治疗在增强 VILI 后的恢复方面具有治疗潜力。
