Combined Mesenchymal Stromal Cell Therapy and Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome. A Randomized Controlled Trial in Sheep

Abstract

on behalf of the Combining Extracorporeal Life Support and Cell Therapy in Critical Illness (CELTIC) investigators.

Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study

“…Although initially tested in aGVHD, iPSC-derived MSCs may be used in the future for a range of other clinical targets. Encouraging data on the potential utility of iPSC-derived MSCs manufactured using this platform have already been generated in preclinical models of critical limb ischemia 33 , asthma 34,35 , organ transplant rejection 36 and acute respiratory distress syndrome 37 . Furthermore, we note that primary MSCs have been investigated for a wide range of other therapeutic indications, and we hypothesize that iPSC-derived n, number of patients; first response, improvement by at least one aGvHD grade; best response, maximal improvement in aGvHD grade.…”

MSC Based Therapies to Prevent or Treat BPD—A Narrative Review on Advances and Ongoing Challenges

“…Of course, the criticism of studies in mouse models is justified as none of the actual therapeutics evolved from studies in mice [ 116 ]. As for all other new therapies, a careful and complete evaluation of MSC-based approaches covering the lung microenvironment and the comprehensive documentation of side effects under particular conditions like the recently described increased pulmonary artery embolism in a sheep extracorporeal membrane oxygenation model of acute respiratory distress syndrome is indispensable [ 117 , 118 ]. On the other hand, even a much lower efficacy in preterm infants can alleviate the tremendous disease burden of BPD where the best available medical approaches need a number of 10 treated infants to prevent one BPD case [ 12 , 20 ].…”

Reply to Zhang and Hei: Mesenchymal Stem Cell–derived Exosomes: Are They Another Therapeutic Method for Extracorporeal Membrane Oxygenation–supported Acute Respiratory Distress Syndrome?

“…Paracrine actions are the principle means by which MSCs exert benefit in ARDS, although several alternative mechanisms have been described, such as mitochondrial transfer from MSCs to damaged alveolar epithelial cells (7). The inability of secretome-based therapies to reproduce these actions may limit their efficacy (8,9) Copyright © 2020 by the American Thoracic Society like those used in our study (1). With specific regard to our study, the observation that pulmonary emboli were more frequent in the iPSC-derived MSC group, may not be uniquely associated with the use of a cell-based therapy.…”