In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome. (18th August 2015)

• Record Type: Journal Article
• Authors: Simonson, Oscar E.; Mougiakakos, Dimitrios; Heldring, Nina; Bassi, Giulio; Johansson, Henrik J.; Dalén, Magnus; Jitschin, Regina; Rodin, Sergey; Corbascio, Matthias; El Andaloussi, Samir; Wiklander, Oscar P.B.; Nordin, Joel Z.; Skog, Johan; Romain, Charlotte; Koestler, Tina; Hellgren-Johansson, Laila; Schiller, Petter; Joachimsson, Per-Olof; Hägglund, Hans; Mattsson, Mattias; Lehtiö, Janne; Faridani, Omid R.; Sandberg, Rickard; Korsgren, Olle; Krampera, Mauro; Weiss, Daniel J.; Grinnemo, Karl-Henrik; Le Blanc, Katarina
• Is Part Of: Stem cells translational medicine. Volume 4:Number 10(2015)
• Page Start: 1199
• Page End: 1213
• Publication Date: 2015-08-18
• Subjects: Acute respiratory distress syndrome -- Pulmonary diseases -- Respiratory tract -- Stem cells -- Cell transplantation -- Bone marrow stromal cells -- Cellular therapy -- Clinical translation; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2015-0021
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract : A detailed analysis was performed of the immunomodulatory and proteomic profiles of mesenchymal stromal cells (MSCs) administered to two patients with refractory acute respiratory distress syndrome (ARDS). The respiratory, hemodynamic, and multiorgan failure resolved and multiple pulmonary and systemic inflammation markers decreased. These observations highlight the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. Abstract: : Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2 × 10 6 cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. Significance: This article describes the cases of two patients with severe refractory adult respiratory syndrome (ARDS) who failed to improve after both standard life support measures, including mechanical ventilation, and additional measures, including extracorporeal ventilation (i.e., in a heart-lung machine). Unlike acute forms of ARDS (such in the current NIH-sponsored study of mesenchymal stromal cells in ARDS), recovery does not generally occur in such patients.