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A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis

Argyris Tzouvelekis1, Vassilis Paspaliaris2, George Koliakos34, Paschalis Ntolios1, Evangelos Bouros5, Anastasia Oikonomou6, Athanassios Zissimopoulos7, Nikolaos Boussios7, Brian Dardzinski34, Dimitrios Gritzalis8, Antonis Antoniadis9, Marios Froudarakis1, George Kolios5 and Demosthenes Bouros110*

Author Affiliations

1 Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece

2 Adistem Ltd., Wanchai, Hong Kong

3 Hellenic National research foundation stem cell bank, Athens, Greece

4 Biohellenika SA, Thessaloniki, Greece

5 Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece

6 Department of Radiology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece

7 Department of Nuclear Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece

8 Iaso General Hospital, Athens, Greece

9 Department of Pneumonology, General Hospital of Serres, Serres, Greece

10 Department of Pneumonology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis 68100, Greece

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Journal of Translational Medicine 2013, 11:171  doi:10.1186/1479-5876-11-171

Published: 15 July 2013

Abstract

Introduction

Regenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their use for the treatment of this dismal disease.

Patients and methods

To this end, we conducted a phase Ib, non-randomized, clinical trial to study the safety of three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)-stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per infusion) in patients with IPF (n=14) of mild to moderate disease severity (forced vital capacity –FVC>50% predicted value and diffusion lung capacity for carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence of treatment emergent adverse events within 12 months. Alterations of functional, exercise capacity and quality of life parameters at serial time points (baseline, 6 and 12 months after first infusion) were exploratory secondary end-points.

Results

No cases of serious or clinically meaningful adverse events including short-term infusional toxicities as well as long-term ectopic tissue formation were recorded in all patients. Detailed safety monitoring through several time-points indicated that cell-treated patients did not deteriorate in both functional parameters and indicators of quality of life.

Conclusions

The clinical trial met its primary objective demonstrating an acceptable safety profile of endobronchially administered autologous ADSCs-SVF. Our findings accelerate the rapidly expanded scientific knowledge and indicate a way towards future efficacy trials.

Keywords:
Adipose derived stromal cells; Mesenchymal stem cells; Idiopathic pulmonary fibrosis; Safety; Clinical trial; Stromal vascular fraction