Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal

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• 作者：Argyris Tzouvelekis (1)
  George Koliakos (2)
  Paschalis Ntolios (3)
  Irene Baira (3)
  Evangelos Bouros (3)
  Anastasia Oikonomou (4)
  Athanassios Zissimopoulos (5)
  George Kolios (3)
  Despoina Kakagia (6)
  Vassilis Paspaliaris (7)
  Ioannis Kotsianidis (8)
  Marios Froudarakis (1)
  Demosthenes Bouros (1)
  
• 关键词：stem cells ; adipose tissue ; stromal vascular fraction ; idiopathic pulmonary fibrosis ; therapy ; endobronchial infusion ; prospective ; nonrandomized phase Ib clinical trial
• 刊名：Journal of Translational Medicine
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：9
• 期：1
• 全文大小：687KB
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• 作者单位：Argyris Tzouvelekis (1)
  George Koliakos (2)
  Paschalis Ntolios (3)
  Irene Baira (3)
  Evangelos Bouros (3)
  Anastasia Oikonomou (4)
  Athanassios Zissimopoulos (5)
  George Kolios (3)
  Despoina Kakagia (6)
  Vassilis Paspaliaris (7)
  Ioannis Kotsianidis (8)
  Marios Froudarakis (1)
  Demosthenes Bouros (1)
  
  1. Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
  2. Department of Biochemistry, Medical School, Aristotle鈥檚 University of Thessaloniki, Thessaloniki, Greece
  3. Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
  4. Department of Radiology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
  5. Department of Nuclear Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
  6. 1st Department of Gebneral Surgery, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
  7. Adistem Ltd., Wanchai, Hong Kong
  8. Department of Hematology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
  

文摘

Background Idiopathic pulmonary fibrosis represents a lethal form of progressive fibrotic lung disorder with gradually increasing incidence worldwide. Despite intense research efforts its pathogenesis is still elusive and controversial reflecting in the current disappointing status regarding its treatment. Patients and Methods: We report the first protocol proposal of a prospective, unicentric, non-randomized, phase Ib clinical trial to study the safety and tolerability of the adipose-derived stem cells (ADSCs) stromal vascular fraction (SVF) as a therapeutic agent in IPF. After careful patient selection based on functional criteria (forced vital capacity-FVC > 50%, diffuse lung capacity for carbon monoxide-DLCO > 35% of the predicted values) all eligible subjects will be subjected to lipoaspiration resulting in the isolation of approximately 100- 500 gr of adipose tissue. After preparation, isolation and labelling ADSCs-SVF will be endobronchially infused to both lower lobes of the fibrotic lungs. Procedure will be repeated thrice at monthly intervals. Primary end-point represent safety and tolerability data, while exploratory secondary end-points include assessment of clinical functional and radiological status. Results: Preliminary results recently presented in the form of an abstract seem promising and tantalizing since there were no cases of clinically significant allergic reactions, infections, disease acute exacerbations or ectopic tissue formation. In addition 6 months follow-up data revealed a marginal improvement at 6-minute walking distance and forced vital capacity. Conclusions Adipose tissue represents an abundant, safe, ethically uncontested and potentially beneficial source of stem cells for patients with IPF. Larger multicenter phase II and III placebo-controlled clinical trials are sorely needed in order to prove efficacy. However, pilot safety studies are of major importance and represent the first hamper that should be overcome to establish a rigid basis for larger clinical trials.