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A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema.

ABSTRACT: Mesenchymal stromal cells (MSCs) may reduce inflammation and promote tissue repair in pulmonary emphysema.To study the safety and feasibility of bone marrow-derived autologous (BM-) MSC intravenous administration to patients with severe emphysema.A phase I, prospective open-label study registered at ClinicalTrials.gov as NCT01306513 Eligible patients had lung volume reduction surgery (LVRS) on two separate occasions. During the first LVRS bone marrow was collected, from which MSCs were isolated and expanded ex vivo After 8 weeks, patients received two autologous MSC infusions 1 week apart, followed by the second LVRS procedure at 3 weeks after the second BM-MSC infusion.Up to 3 weeks after the last MSC infusion adverse events were recorded. Using immunohistochemistry and qPCR for analysis of cell and proliferation markers, emphysematous lung tissue obtained during the first surgery was compared with lung tissue obtained after the second surgical session to assess BM-MSC effects.From 10 included patients three were excluded: two did not receive MSCs due to insufficient MSC culture expansion, and one had no second surgery. No adverse events related to MSC infusions occurred and lung tissue showed no fibrotic responses. After LVRS and MSC infusions alveolar septa showed a 3-fold increased expression of the endothelial marker CD31 (P ?= ?0.016).Autologous MSC treatment in severe emphysema is feasible and safe. The increase in CD31 expression after LVRS and MSC treatment suggests responsiveness of microvascular endothelial cells in the most severely affected parts of the lung.

SUBMITTER: Stolk J

PROVIDER: S-EPMC4888332 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema.

Stolk J J Broekman W W Mauad T T Zwaginga J J JJ Roelofs H H Fibbe W E WE Oostendorp J J Bajema I I Versteegh M I M MI Taube C C Hiemstra P S PS

QJM : monthly journal of the Association of Physicians 20160127 5

<h4>Background</h4>Mesenchymal stromal cells (MSCs) may reduce inflammation and promote tissue repair in pulmonary emphysema.<h4>Aim</h4>To study the safety and feasibility of bone marrow-derived autologous (BM-) MSC intravenous administration to patients with severe emphysema.<h4>Design</h4>A phase I, prospective open-label study registered at ClinicalTrials.gov as NCT01306513 Eligible patients had lung volume reduction surgery (LVRS) on two separate occasions. During the first LVRS bone marrow ...[more]

PMID: 26819296

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Project description: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. Stem Cells Translational Medicine 2017;6:962-969.

Dataset Information

A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema.

Publications

A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema.

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