Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels

Respir Res. 2021 May 8;22(1):142. doi: 10.1186/s12931-021-01734-8.


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.

Keywords: C-reactive protein; Chronic obstructive pulmonary disease; Inflammation; Mesenchymal stromal cells; Pulmonary function.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biological Products / adverse effects
  • Biological Products / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Exercise Tolerance
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung / metabolism
  • Lung / physiopathology*
  • Male
  • Mesenchymal Stem Cell Transplantation* / adverse effects
  • Mesenchymal Stem Cells
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / surgery*
  • Recovery of Function
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Vital Capacity


  • Biological Products
  • Biomarkers
  • C-Reactive Protein
  • remestemcel-l

Associated data

  • ClinicalTrials.gov/NCT00683722