TY - JOUR
T1 - Feasibility and Safety of Low-Dose Mesenchymal Stem Cell Infusion in Lung Transplant Recipients
AU - Erasmus, David Brett
AU - Durand, Nisha
AU - Alvarez, Francisco A.
AU - Narula, Tathagat
AU - Hodge, David O.
AU - Zubair, Abba C.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press.
PY - 2022/9
Y1 - 2022/9
N2 - Background: We have previously shown bone marrow-derived mesenchymal stem cells (MSCs) may shift immune responses toward anti-inflammatory pathways and stabilize the course of obstructive chronic lung allograft syndrome (o-CLAD) after lung transplantation. In this study, we measured the response of lower dose infusions. Methods: We infused low-dose MSCs intravenously in 13 patients who had developed moderate-to-severe o-CLAD. Three had previously received an infusion of MSCs from a different donor and were re-dosed at 1 × 106 MSC/kg, while 5 received a first dose at 1 × 106 MSC/kg and five received an even lower dose at 0.5 × 106 MSC/kg. We recorded pulmonary function tests before and after infusion, and patients were followed clinically for 12 months. Results: Infusions were well tolerated, and no significant adverse events were recorded in the first 30 days. There was significant decline (mean ± SD) in forced vital capacity (FVC) (3.49 ± 1.03 vs 3.18 ± 0.94 L, P =. 03) and forced expiratory volume in 1 second (FEV1) (2.28 ± 0.86 vs 1.77 ± 0.49 L, P =. 04) over the year preceding infusion. FVC (3.18 ± 0.94 vs 3.46 ± 0.99 L, P =. 53) and FEV1 was not significantly changed (1.77 ± 0.49 vs 1.88 ± 0.75, P =. 72) when comparing values immediately prior to infusion to those obtained 1 year after infusion, indicating a possible stabilizing effect on lung function decline due to o-CLAD. Conclusion: Intravenous infusions of bone marrow-derived MSCs are well tolerated in lung transplant recipients with moderate-to-severe CLAD. Low-dose MSCs appear to slow progression of CLAD in some patients.
AB - Background: We have previously shown bone marrow-derived mesenchymal stem cells (MSCs) may shift immune responses toward anti-inflammatory pathways and stabilize the course of obstructive chronic lung allograft syndrome (o-CLAD) after lung transplantation. In this study, we measured the response of lower dose infusions. Methods: We infused low-dose MSCs intravenously in 13 patients who had developed moderate-to-severe o-CLAD. Three had previously received an infusion of MSCs from a different donor and were re-dosed at 1 × 106 MSC/kg, while 5 received a first dose at 1 × 106 MSC/kg and five received an even lower dose at 0.5 × 106 MSC/kg. We recorded pulmonary function tests before and after infusion, and patients were followed clinically for 12 months. Results: Infusions were well tolerated, and no significant adverse events were recorded in the first 30 days. There was significant decline (mean ± SD) in forced vital capacity (FVC) (3.49 ± 1.03 vs 3.18 ± 0.94 L, P =. 03) and forced expiratory volume in 1 second (FEV1) (2.28 ± 0.86 vs 1.77 ± 0.49 L, P =. 04) over the year preceding infusion. FVC (3.18 ± 0.94 vs 3.46 ± 0.99 L, P =. 53) and FEV1 was not significantly changed (1.77 ± 0.49 vs 1.88 ± 0.75, P =. 72) when comparing values immediately prior to infusion to those obtained 1 year after infusion, indicating a possible stabilizing effect on lung function decline due to o-CLAD. Conclusion: Intravenous infusions of bone marrow-derived MSCs are well tolerated in lung transplant recipients with moderate-to-severe CLAD. Low-dose MSCs appear to slow progression of CLAD in some patients.
KW - Th1/Th2
KW - adult human bone marrow
KW - lung
KW - mesenchymal stem cells
KW - transplantation
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U2 - 10.1093/stcltm/szac051
DO - 10.1093/stcltm/szac051
M3 - Article
C2 - 35881142
AN - SCOPUS:85138459647
SN - 2157-6564
VL - 11
SP - 891
EP - 899
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 9
ER -