Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels.
Respir Res
; 22(1): 142, 2021 May 08.
Article
em En
| MEDLINE
| ID: mdl-33964910
ABSTRACT
BACKGROUND:
We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels.METHODS:
Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels.RESULTS:
In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups.CONCLUSION:
In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases. TRIAL REGISTRATION Clinicaltrials.gov NCT00683722.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Proteína C-Reativa
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Doença Pulmonar Obstrutiva Crônica
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Transplante de Células-Tronco Mesenquimais
/
Pulmão
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Respir Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos