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

Abstract

Selma Denis Squassoni, 1 Eliseo Joji Sekiya, 2,* Elie Fiss, 1, 3 Monica Silveira Lapa, 1 Daniela dos Santos Cayetano, 2 Flávia Nascimento, 2 Adelson Alves, 2 Nadine Cristina Machado, 1 Bruna Escaramboni, 4 Francislaine Aparecida dos Reis Lívero, 5 Maria José Malagutti-Ferreira, 4 Murilo Racy Soares, 6 Francisco Winter dos Santos Figueiredo, 1 Beatriz Kimberly Nath Kramer, 4 Priscila Megda João Job Zago, 5 João Tadeu Ribeiro-Paes 4,* 1ABC Medical School, São Paulo, SP, Brazil; 2São Lucas Research and Education Institute (IEP-Sao Lucas), TechLife, São Paulo, SP, Brazil; 3Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil; 4São Paulo State University (UNESP), Assis, SP, Brazil; 5Paranaense University (UNIPAR), Umuarama, PR, Brazil; 6Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, SP, Brazil*These authors contributed equally to this workCorrespondence: João Tadeu Ribeiro-PaesDepartment of Biotechnology, São Paulo State University - UNESP, Avenida Dom Antônio, 2100, Assis, SP, 19806-900, BrazilTel [phone]Email [email protected] Joji SekiyaIEP-São Lucas - TechLife, Avenida Arnolfo de Azevedo, 108 - Pacaembu, São Paulo, SP, 01236-030, BrazilTel [phone]Email [email protected] 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.Keywords: COPD, cell therapy, stem cells, mesenchymal stem cells, concomitant infusion, co-infusion

Keywords

• copd
• cell therapy
• stem cells
• mesenchymal stem cells
• concomitant infusion
• co-infusion