title: Combined Bone Marrow-Derived Mesenchymal Stromal Cell Therapy and One-Way Endobronchial Valve Placement in Patients with Pulmonary Emphysema: A Phase I Clinical Trial.
abstract: One-way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients. However, local inflammation may result and can contribute to worsening of clinical status in these patients. We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients. This initial study sought to investigate the safety of this approach. For this purpose, a phase I, prospective, patient-blinded, randomized, placebo-controlled design was used. Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow-derived MSCs (108cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one-way EBVs. Patients were evaluated 1, 7, 30, and 90 days after therapy. All patients completed the study protocol and 90-day follow-up. MSC delivery did not result in acute administration-related toxicity, serious adverse events, or death. No significant between-group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease. Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes. However, quality-of-life indicators were higher in EBV + MSC compared with EBV. EBV + MSC patients presented decreased levels of circulating C-reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores. Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy. Stem Cells Translational Medicine 2017;6:962-969.
authors.affiliation: Hospital Moinhos de Vento (HMV), Porto Alegre, Rio Grande do Sul, Brazil.|Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Hugo Goulart
authors.initials: HG
authors.lastname: de Oliveira
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro-RJ, Brazil.
authors.forename: Fernanda Ferreira
authors.initials: FF
authors.lastname: Cruz
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro-RJ, Brazil.
authors.forename: Mariana Alves
authors.initials: MA
authors.lastname: Antunes
authors.affiliation: Hospital Moinhos de Vento (HMV), Porto Alegre, Rio Grande do Sul, Brazil.|Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Amarilio Vieira
authors.initials: AV
authors.lastname: de Macedo Neto
authors.affiliation: Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Guilherme Augusto
authors.initials: GA
authors.lastname: Oliveira
authors.affiliation: Hospital Moinhos de Vento (HMV), Porto Alegre, Rio Grande do Sul, Brazil.|Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Fabio Munhoz
authors.initials: FM
authors.lastname: Svartman
authors.affiliation: Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Tamara
authors.initials: T
authors.lastname: Borgonovo
authors.affiliation: Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Carmen Lucia Kuniyoshi
authors.initials: CL
authors.lastname: Rebelatto
authors.affiliation: Vermont Lung Center, College of Medicine, University of Vermont, Burlington, Vermont, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.affiliation: Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Paulo Roberto Slud
authors.initials: PR
authors.lastname: Brofman
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro-RJ, Brazil.
authors.forename: Marcelo Marcos
authors.initials: MM
authors.lastname: Morales
authors.affiliation: Hospital Universitário Clementino Fraga Filho/UFRJ, Rio de Janeiro-RJ, Brazil.
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Lapa E Silva
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro-RJ, Brazil.
authors.forename: Patricia Rieken Macedo
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D011664:Pulmonary Valve / Q000502:physiology*; D011788:Quality of Life; D012129:Respiratory Function Tests; D016896:Treatment Outcome
chemical_list: D002097:C-Reactive Protein
keywords: Chronic obstructive pulmonary disease; Endobronchial valves; Lung volume reduction; Mesenchymal stromal cells; Spirometry