TY - JOUR
T1 - Intravenous Autologous Bone Marrow–derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine
AU - Batchinsky, Andriy I.
AU - Roberts, Teryn R.
AU - Antebi, Ben
AU - Necsoiu, Corina
AU - Choi, Jae H.
AU - Herzig, Maryanne
AU - Cap, Andrew P.
AU - McDaniel, Jennifer S.
AU - Rathbone, Christopher R.
AU - Chung, Kevin K.
AU - Cancio, Leopoldo C.
N1 - Publisher Copyright:
Copyright © 2023 by the American Thoracic Society.
PY - 2023/12/15
Y1 - 2023/12/15
N2 - Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow–derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 6 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 3 106 white blood cells and a mean of 56.6 3 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 3 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 6 10 h) versus control animals (14 6 2 h) (P = 0.004), reduced ARDS severity at 24 (P, 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-a (tumor necrosis factor-a). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow–derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.
AB - Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow–derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 6 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 3 106 white blood cells and a mean of 56.6 3 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 3 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 6 10 h) versus control animals (14 6 2 h) (P = 0.004), reduced ARDS severity at 24 (P, 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-a (tumor necrosis factor-a). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow–derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.
KW - ARDS
KW - MSCs
KW - burns
KW - smoke inhalation injury
KW - swine
UR - http://www.scopus.com/inward/record.url?scp=85180014787&partnerID=8YFLogxK
U2 - 10.1164/rccm.202305-0865OC
DO - 10.1164/rccm.202305-0865OC
M3 - Article
C2 - 37797214
AN - SCOPUS:85180014787
SN - 1073-449X
VL - 208
SP - 1283
EP - 1292
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 12
ER -