Millar, Jonathan Edward and Bartnikowski, Nicole and Passmore, Margaret R. and Obonyo, Nchafatso G. and Malfertheiner, Maximillian and von Bahr, Viktor and Redd, Meredith A. and Hoe, Louise See and Ki, Katrina K. and Pedersen, Sanne and Boyle, Andrew J. and Baillie, J. Kenneth and Shekar, Kiran and Palpant, Nathan and Suen, Jacky Y. and Matthay, Michael A. and McAuley, Daniel F. and Fraser, John F. (2020) Combined Mesenchymal Stromal Cell Therapy and Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome A Randomized Controlled Trial in Sheep. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 202 (3). pp. 383-392. ISSN 1073-449X, 1535-4970
Full text not available from this repository. (Request a copy)Abstract
Rationale: Mesenchymal stromal cell (MSC) therapy is a promising intervention for acute respiratory distress syndrome (ARDS), although trials to date have not investigated its use alongside extracorporeal membrane oxygenation (ECMO). Recent preclinical studies have suggested that combining these interventions may attenuate the efficacy of ECMO. Objectives: To determine the safety and efficacy of MSC therapy in a model of ARDS and ECMO. Methods: ARDS was induced in 14 sheep, after which they were established on venovenous ECMO. Subsequently, they received either endobronchial induced pluripotent stem cell-derived human MSCs (hMSCs) (n = 7) or cell-free carrier vehicle (vehicle control; n = 7). During ECMO, a low VT ventilation strategy was employed in addition to protocolized hemodynamic support. Animals were monitored and supported for 24 hours. Lung tissue, bronchoalveolar fluid, and plasma were analyzed, in addition to continuous respiratory and hemodynamic monitoring. Measurements and Main Results: The administration of hMSCs did not improve oxygenation (Pa-O2/FIO2 mean difference = -146 mm Hg; P= 0.076) or pulmonary function. However, histological evidence of lung injury(lung injuryscoremeandifference = -0.07; P= 0.04) and BALIL-8 were reduced. In addition, hMSC-treated animals had a significantly lower cumulative requirement for vasopressor. Despite endobronchial administration, animals treated with hMSCs had a significant elevation in transmembrane oxygenator pressure gradients. Thiswas accompanied by more pulmonary artery thromboses and adherent hMSCs found on explanted oxygenator fibers. Conclusions: Endobronchial hMSC therapy in an ovine model of ARDS and ECMO can impair membrane oxygenator function and does not improve oxygenation. These data do not recommend the safe use of hMSCs during venovenous ECMO.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE LUNG INJURY; STEM-CELLS; SECRETION; ARDS; ARDS; ECMO; MSC; models; animal |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Mar 2021 10:28 |
| Last Modified: | 17 Mar 2021 10:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44105 |
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