Autologous Infusion of Bone Marrow and Mesenchymal Stromal Cells in Patients with Chronic Obstructive Pulmonary Disease: Phase I Randomized Clinical Trial

Abstract

Background and Objectives Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms. There is no curative clinical treatment for COPD. In this context, cell-based therapy is a promising therapeutic alternative for COPD. Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD. The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association. Methods To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group – patients receiving conventional treatment; BMMC group – patients receiving only BMMC; ADSC group – patients receiving only ADSC, and co-infusion group – patients receiving the concomitant infusion of BMMC and ADSC. Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up. Results No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion. In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures. Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO). Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life. Conclusion The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD. However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented.

Stem Cell-Based Regenerative Therapy and Derived Products in COPD: A Systematic Review and Meta-Analysis

“…Of the 415 potentially relevant records identified in the initial search, 14 studies [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] were deemed eligible for a qualitative synthesis. Since 3 studies [ 48 , 49 , 50 ] reported non-extractable data on efficacy outcomes, the quantitative synthesis (pairwise meta-analysis) was carried out on 11 studies [ 46 , 47 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

“…Of the 415 potentially relevant records identified in the initial search, 14 studies [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] were deemed eligible for a qualitative synthesis. Since 3 studies [ 48 , 49 , 50 ] reported non-extractable data on efficacy outcomes, the quantitative synthesis (pairwise meta-analysis) was carried out on 11 studies [ 46 , 47 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. The effect estimates of the pairwise meta-analysis were obtained from 371 COPD patients selected from 6 non-randomized, non-controlled clinical trials [ 46 , 47 , 52 , 53 , 54 , 55 ], 3 RCTs [ 56 , 57 , 58 ], and 2 observational cohort studies [ 51 , 59 ].…”

“…Since 3 studies [ 48 , 49 , 50 ] reported non-extractable data on efficacy outcomes, the quantitative synthesis (pairwise meta-analysis) was carried out on 11 studies [ 46 , 47 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. The effect estimates of the pairwise meta-analysis were obtained from 371 COPD patients selected from 6 non-randomized, non-controlled clinical trials [ 46 , 47 , 52 , 53 , 54 , 55 ], 3 RCTs [ 56 , 57 , 58 ], and 2 observational cohort studies [ 51 , 59 ]. The relevant patient demographics, study characteristics, and Jadad score have been summarized in Table 1 .…”

“…All the RCTs [ 56 , 57 , 58 ] included in the pairwise meta-analysis were ranked as being of medium- to high-quality, in accordance with the Jadad score. Two studies [ 56 , 57 ] were of medium quality (Jadad score = 3) and one [ 58 ] was of high quality (Jadad > 3).…”

“…All the RCTs [ 56 , 57 , 58 ] included in the pairwise meta-analysis were ranked as being of medium- to high-quality, in accordance with the Jadad score. Two studies [ 56 , 57 ] were of medium quality (Jadad score = 3) and one [ 58 ] was of high quality (Jadad > 3). The traffic light plot for the assessment of each included RCT is reported in Figure 4 A and the weighted plot for the assessment of the overall risk of bias by domains is shown in Figure 4 B.…”