Chest
Volume 143, Issue 6, June 2013, Pages 1590-1598
Journal home page for Chest

Original Research
COPD
A Placebo-Controlled, Randomized Trial of Mesenchymal Stem Cells in COPD

https://doi.org/10.1378/chest.12-2094Get rights and content

Abstract

Background

COPD is a devastating disease affecting millions worldwide. As disease pathogenesis includes both chronic pulmonary and systemic inflammation, antiinflammatory effects of systemically administered mesenchymal stem cells (MSCs) may decrease inflammation, resulting in improved lung function and quality of life. The goal of this study was to assess safety and to perform an initial evaluation of the potential efficacy of systemic MSC administration to patients with moderate to severe COPD.

Methods

Sixty-two patients at six sites were randomized to double-blinded IV infusions of either allogeneic MSCs (Prochymal; Osiris Therapeutics Inc) or vehicle control. Patients received four monthly infusions (100 × 106 cells/infusion) and were subsequently followed for 2 years after the first infusion. End points included comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, 6MWT, and assessments of systemic inflammation.

Results

All study patients completed the full infusion protocol, and 74% completed the 2-year follow-up. There were no infusional toxicities and no deaths or serious adverse events deemed related to MSC administration. There were no significant differences in the overall number of adverse events, frequency of COPD exacerbations, or worsening of disease in patients treated with MSCs. There were no significant differences in PFTs or quality-of-life indicators; however, an early, significant decrease in levels of circulating C-reactive protein (CRP) was observed in patients treated with MSCs who had elevated CRP levels at study entry.

Conclusions

Systemic MSC administration appears to be safe in patients with moderate to severe COPD and provides a basis for subsequent cell therapy investigations.

Section snippets

Study Design and Oversight

A prospective, randomized, double-blind, placebo (vehicle)-controlled design was used, and participants were recruited from six different institutions in the United States. The study was approved by the institutional review board for each participating center and written informed consent obtained from each participant. An independent data and safety monitoring board approved all amendments and oversaw conduct of the trial. The study (NCT00683722) was conducted in accordance with the amended

Patients

All 62 randomized patients completed all four Prochymal infusions (intent-to-treat population). The baseline characteristics of the intent-to-treat populations are summarized in Table 2, Table 3. The two treatment groups were generally well matched, although the patients receiving MSCs tended to be older than the patients receiving placebo (mean age, 68.1 years vs 64.1 years, respectively) and there were more current smokers in the placebo group (37.5% placebo group vs 16.7% MSC group). The

Discussion

Administration of either autologous or non-HLA-matched allogeneic MSCs is increasingly being investigated as a potential therapeutic intervention for a range of inflammatory and immune diseases. Clinical trials to date have demonstrated safety of systemic MSC infusion and, thus far, there do not appear to be any significant AEs in follow-up periods lasting for several years in a variety of patient populations.9., 10., 11., 12., 35. Concerns of special interest, including ectopic tissue

Acknowledgments

Author contributions: Dr Weiss had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Weiss: contributed to study design, data acquisition and interpretation, drafting and revising the article, and final approval of the article; and served as principle author.

Dr Casaburi: contributed to data acquisition and interpretation, drafting and revising the article, and final approval of the article.

Ms Flannery:

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    Preliminary results of this study were presented at the Stem Cells and Cell Therapies in Lung Biology and Diseases Conference, July 2011, Burlington, VT.

    Funding/Support: Osiris Therapeutics Inc provided funding for the investigation.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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