Autologous Peripheral Blood Mononuclear Cells as Treatment in Refractory Acute Respiratory Distress Syndrome

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a devastating disorder. Despite enormous efforts in clinical research, effective treatment options are lacking, and mortality rates remain unacceptably high. Objectives: A male patient with severe ARDS showed no clinical improvement with conventional therapies. Hence, an emergent experimental intervention was performed. Methods: We performed intratracheal administration of autologous peripheral blood-derived mononuclear cells (PBMCs) and erythropoietin (EPO). Results: We found that after 2 days of initial PBMC/EPO application, lung function improved and extracorporeal membrane oxygenation (ECMO) support was reduced. Bronchoscopy and serum inflammatory markers revealed reduced inflammation. Additionally, serum concentration of miR-449a, b, c and miR-34a, a transient upregulation of E-cadherin and associated chromatin marks in PBMCs indicated airway epithelial differentiation. Extracellular vesicles from PBMCs demonstrated anti-inflammatory capacity in a TNF-a-mediated nuclear factor-κB in vitro assay. Despite improving respiratory function, the patient died of multisystem organ failure on day 38 of ECMO treatment. Conclusions: This case report provides initial encouraging evidence to use locally instilled PBMC/EPO for treatment of severe refractory ARDS. The observed clinical improvement may partially be due to the anti-inflammatory effects of PBMC/EPO to promote tissue regeneration. Further studies are needed for more in-depth understanding of the underlying mechanisms of in vivo regeneration.

Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance

“…MSC use during ECMO has been described previously but has either been administered before the commencement of ECMO,7 by intratracheal administration8 or during a pause in flow 4. These methods of administration may not always be possible in severely ill patients with ARDS who are reliant on continuous high-flow ECMO for oxygenation.…”

Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells

“…Cell therapy has been proven as an effective method for injury treatment [ 1 - 4 ]. Although considerable advances were made, current understanding of the mechanisms of transplanted cell therapeutic effects is incomplete.…”

Blockade of Interleukin‐17 Restrains the Development of Acute Lung Injury

“…Despite extensive investigation aimed at early diagnostic and pathogenetic factors of ALI, current management is mainly supportive, as specific therapies have not been identified . Animal models focused on ALI pathogenesis have yielded insights into mechanisms that initiate injury; however, little is known about potential determinants of resolution . Thus, new strategies are still required for achieving effective treatment of ALI, which might ultimately aid the clinical therapy for patients with ARDS.…”