BIO15: Hemocompatibility Evaluation of a Novel Pulmonary Assist System Using the Lightweight, Axial-Flow CDX Pump During Venovenous ECMO

Abstract

The next-generation of mesenchymal stromal cell (MSC) therapies aim to enhance efficacy via in vitro licensing. Various stimuli initiate immune regulation and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants, prior to administration. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS = 4, 8, and 12 dyne/cm2) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of classical pro-inflammatory cytokines. A modular parallel plate bioreactor was designed in CAD software to apply precise WSS upon adherent MSC populations. The novel bioreactor's inlet and outlet geometries were iteratively designed until computational fluid dynamic simulations confirmed >95% of the channel surface area experienced the target WSS +/-1 dyne/cm2. In vitro studies showed a dose-dependent effect of WSS on potency, evidenced by adipose tissue and bone marrow-derived MSC production of prostaglandin E2 (PGE2) and indoleamine 2,3 dioxygenase 1 (IDO1). Consistent, reproducible licensing occurred with significant impacts on cell viability and cellular yield at greater WSS magnitudes. These results suggest mechanotransduction as a viable, scalable pre-conditioning alternative to pro-inflammatory cytokines. Enhancing the immunomodulatory capacity of MSC via biomechanical conditioning represents a novel cell therapy manufacturing approach.