Cell Therapy for Idiopathic Pulmonary Fibrosis: Rationale and Progress to Date
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Cell Therapy for Idiopathic Pulmonary Fibrosis: Rationale and Progress to Date Paschalis Ntolios1,4 · Paschalis Steiropoulos1 · Georgia Karpathiou3 · Stavros Anevlavis1 · Theodoros Karampitsakos2 · Evangelos Bouros2 · Marios E. Froudarakis1 · Demosthenes Bouros2 · Argyrios Tzouvelekis2
© Springer Nature Switzerland AG 2020
Abstract Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive lung scarring due to unknown injurious stimuli ultimately leading to respiratory failure. Diagnosis is complex and requires a combination of clinical, laboratory, radiological, and histological investigations, along with exclusion of known causes of lung fibrosis. The current understanding of the disease etiology suggests an interaction between genetic factors and epigenetic alterations in susceptible, older individuals. Prognosis is dismal and current treatment options include anti-fibrotic agents that only slow down disease progression and carry considerable side effects that hamper patients’ quality of life. Therefore, there is a need for new, more effective treatments, alone or in combination with existing pharmacotherapy. Regenerative medicine, the potential use of cell therapies to treat destructive diseases that cause architectural distortion to the target organ, has also emerged as an alternative therapeutic for lung diseases with unfavorable prognosis such as IPF. Mesenchymal stem cells (MSCs) and type II alveolar epithelial cells (AEC2s) have been used and their safety has been demonstrated. In the case of MSCs, both homogenic and allogeneic sources have been used and both are considered viable options without immunosuppressive therapy, taking into consideration the absence of immunogenicity and HLA response. AEC2s have been used in one trial with promising results but their use requires a deceased donor and immunosuppressive pre-treatment. In this review, we briefly summarize the current state of knowledge regarding the pathogenesis of IPF, and the background and rationale for using MSCs or AEC2s as potential treatment options. We list and describe the clinical trials completed to date and provide a comparison of their methods and results as well as a possible way forward.
1 Introduction Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) characterized by lung scarring of the interstitium that eventually leads to parenchymal destruction and loss of normal function [1, 2]. It affects mainly men * Paschalis Ntolios [email protected] 1
Department of Respiratory Medicine, Medical School of Alexandroupolis, Democritus University of Thrace, Alexandroupolis 68100, Greece
2
First Academic Department of Pneumonology, National and Kapodistrian University of Athens, Athens, Greece
3
Department of Pathology, University Hospital of Saint-Etienne, Saint‑Etienne, France
4
Department of Pneumonology, University Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece
aged 60–75 years with a prevalence of 13–20 individuals per 100,
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