Cynata Therapeutics

Gain a direct line to Cynata Therapeutics leadership

Be first to know our latest company updates

Watch exclusive videos accompanying major news

Contact Us

Pre-Clinical Development

Clinical Development

Products & Pipeline

Scientific Publications

Intellectual Property

Cymerus™ Platform

Our technology

Board of Directors

Management team

About us

Company FAQs

Corporate Governance

Analyst Research

Investor FAQs

Financial Reports

Right to Receive Documents

Investor Presentations

Share Price

Announcements

Investors

Updates

Home

Frank Ruhl Libre

Read full article

Rationale: Mesenchymal stromal cell (MSC) therapy is a promising intervention for acute respiratory distress syndrome (ARDS), although trials to date have not investigated its use alongside extracorporeal membrane oxygenation (ECMO). Recent preclinical studies have suggested that combining these interventions may attenuate the efficacy of ECMO.

Objectives: To determine the safety and efficacy of MSC therapy in a model of ARDS and ECMO.

Methods: ARDS was induced in 14 sheep, after which they were established on venovenous ECMO. Subsequently, they received either endobronchial induced pluripotent stem cell–derived human MSCs (hMSCs) (n = 7) or cell-free carrier vehicle (vehicle control; n = 7). During ECMO, a low Vt ventilation strategy was employed in addition to protocolized hemodynamic support. Animals were monitored and supported for 24 hours. Lung tissue, bronchoalveolar fluid, and plasma were analyzed, in addition to continuous respiratory and hemodynamic monitoring.

Measurements and Main Results: The administration of hMSCs did not improve oxygenation (PaO2/FiO2 mean difference = −146 mm Hg; P = 0.076) or pulmonary function. However, histological evidence of lung injury (lung injury score mean difference = −0.07; P = 0.04) and BAL IL-8 were reduced. In addition, hMSC-treated animals had a significantly lower cumulative requirement for vasopressor. Despite endobronchial administration, animals treated with hMSCs had a significant elevation in transmembrane oxygenator pressure gradients. This was accompanied by more pulmonary artery thromboses and adherent hMSCs found on explanted oxygenator fibers.

Conclusions: Endobronchial hMSC therapy in an ovine model of ARDS and ECMO can impair membrane oxygenator function and does not improve oxygenation. These data do not recommend the safe use of hMSCs during venovenous ECMO.

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