Combined Bone Marrow-Derived Mesenchymal Stromal Cell Therapy and One-Way Endobronchial Valve Placement in Patients with Pulmonary Emphysema: A Phase I Clinical Trial

Autor: Hugo Goulart de Oliveira, Amarilio Vieira de Macedo Neto, Fábio Munhoz Svartman, Marcelo M. Morales, Tamara Borgonovo, Carmen Lúcia Kuniyoshi Rebelatto, Fernanda F. Cruz, Patricia R. M. Rocco, José Roberto Lapa e Silva, Paulo Roberto Slud Brofman, Mariana A. Antunes, Guilherme A. P. de Oliveira, Daniel J. Weiss
Rok vydání: 2016
Předmět:
Adult
Male
0301 basic medicine
Spirometry
medicine.medical_specialty
Mesenchymal stromal cells
Endobronchial valves
Mesenchymal Stem Cell Transplantation
Air trapping
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Translational Research Articles and Reviews
Tissue Engineering and Regenerative Medicine
Lung volume reduction
Internal medicine
Concomitant Therapy
medicine
Humans
Adverse effect
Aged
Aged
80 and over
Pulmonary Valve
COPD
medicine.diagnostic_test
business.industry
Chronic obstructive pulmonary disease
Endobronchial valve
Mesenchymal Stem Cells
Cell Biology
General Medicine
Middle Aged
Airway obstruction
medicine.disease
Respiratory Function Tests
Surgery
C-Reactive Protein
Treatment Outcome
030104 developmental biology
medicine.anatomical_structure
Pulmonary Emphysema
030228 respiratory system
Quality of Life
Female
Bone marrow
medicine.symptom
business
Developmental Biology
Zdroj: Stem Cells Translational Medicine
ISSN: 2157-6580
2157-6564
Popis: 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 (108 cells, 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.
Databáze: OpenAIRE
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