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Abstract

We appreciate the thoughtful comments of Drs Thangakunam and Christopher regarding the Allogeneic Human Mesenchymal Stem Cells (MSC) in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial.1Glassberg M. Minkiewicz J. Toonkel R. et al.Allogeneic human mesenchymal stem cells in patients with idiopathic pulmonary fibrosis intravenous delivery (AETHER): a phase I, safety, clinical trial.Chest. 2017; 151: 971-981Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar We continue to support the concept that future studies of IV MSCs should be performed in monitored settings, given the compromised pulmonary function of patients with idiopathic pulmonary fibrosis. Regarding immunologic tolerability of the MSCs, studies to date support the safe administration of allogeneic cells. Importantly, current good manufacturing practice cell production techniques minimize unknown constituents, and washing greatly reduces dimethyl sulfoxide (DMSO) concentrations.2Galmes A. Gutiérrez A. Sampol A. et al.Long-term hematological reconstitution and clinical evaluation of autologous peripheral blood stem cell transplantation after cryopreservation of cells with 5% and 10% dimethylsulfoxide at −80 degrees C in a mechanical freezer.Haematologica. 2007; 92: 986-989Crossref PubMed Scopus (38) Google Scholar, 3Hunt C.J. Armitage S.E. Pegg D.E. Cryopreservation of umbilical cord blood: 2. tolerance of CD34+ cells to multimolar dimethyl sulphoxide and the effect of cooling rate on the recovery after freezing and thawing.Cryobiology. 2003; 46: 76-87Crossref PubMed Scopus (80) Google Scholar, 4Rowley S.D. Anderson G.L. Effect of DMSO exposure without cryopreservation on hematopoietic progenitor cells.Bone Marrow Transplant. 1993; 11: 389-393PubMed Google Scholar In the AETHER trial, subjects were screened for DMSO sensitivity, as the MSCs are exposed to DMSO during their production. We did not note any adverse events related to this reagent. Finally, we agree with the authors that patients with chronic diseases are desperate and will gravitate to experimental treatment modalities, including MSC infusions. As with all medical interventions, patient safety remains the major concern, and efficacy studies need to be conducted before therapeutic labeling can be attached to this intervention, particularly in patients with more severe fibrotic lung disease. We are conducting additional clinical trials at our center at the University of Miami to advance the regulatory approval of allogeneic MSC for patients with idiopathic pulmonary fibrosis and other life-threatening untreatable diseases. Other contributions: We thank Drs Thangakunam and Christopher again for their insights. Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical TrialCHESTVol. 151Issue 5PreviewDespite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow–derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis. Full-Text PDF Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis: Well Done, but Subsequent Doses May Be VitalCHESTVol. 153Issue 1PreviewWe read with interest the article by Glassberg et al1 in a recent issue of CHEST (May 2017). The authors should be congratulated for producing the first groundbreaking scientific evidence regarding the safety of this modality for treatment for idiopathic pulmonary fibrosis. We had previously published our experience of using mesenchymal stem cells (MSC) in a single patient with advanced pulmonary fibrosis that developed from a combination of radiation and drug-induced toxicity.2 We had administered the initial dose of 1 × 108 MSC IV without any problems. Full-Text PDF