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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:Autosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy disease characterized by progressive formation and enlargement of cysts in multiple organs. The kidneys are particularly affected and patients may eventually develop end-stage renal disease (ESRD). We hypothesize that bone marrow mesenchymal stromal cells (BMMSCs) are renotropic and may improve kidney function via anti-apoptotic, anti-fibrotic, and anti-inflammatory effects. In this study, we aim to assess the safety and tolerability of a BMMSC infusion in ADPKD patients.We performed a single-arm phase I clinical trial with a 12-month follow-up. This study enrolled six eligible ADPKD patients with an estimated glomerular filtration rate (eGFR) of 25-60 ml/min/1.73 m2. Patients received autologous cultured BMMSCs (2?×?106 cells/kg) through the cubital vein according to our infusion protocol. We investigated safety issues and kidney function during the follow-up visits, and compared the findings to baseline and 1 year prior to the intervention.There were no patients lost to follow-up. We observed no cell-related adverse events (AE) and serious adverse events (SAE) after 12 months of follow-up. The mean eGFR value of 33.8?±?5.3 ml/min/1.73 m2 1 year before cell infusion declined to 26.7?±?3.1 ml/min/1.73 m2 at baseline (P?=?0.03) and 25.8?±?6.2 ml/min/1.73 m2 at the 12-month follow-up visit (P?=?0.62). The mean serum creatinine (SCr) level of 2?±?0.3 mg/dl 1 year before the infusion increased to 2.5?±?0.4 mg/dl at baseline (P?=?0.04) and 2.5?±?0.6 mg/dl at the 12-month follow-up (P?=?0.96). This indicated significant changes between the differences of these two periods (12 months before infusion to baseline, and 12 months after infusion to baseline) in SCr (P?=?0.05), but not eGFR (P?=?0.09).This trial demonstrated the safety and tolerability of an intravenous transplantation of autologous BMMSCs. BMMSC efficacy in ADPKD patients should be investigated in a randomized placebo-controlled trial with a larger population, which we intend to perform.ClinicalTrials.gov, NCT02166489 . Registered on June 14, 2014.

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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