Cellvation is also developing CEVA-D, a novel bioreactor that enhances the anti-inflammatory potency of bone marrow-derived cells without genetic manipulation. Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury. Our collaborators have previously published data demonstrating that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFjB-COX2-prostaglandin E2 (PGE2) to suppress tumor necrosis factor-a (TNF-a) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1-type activated microglia in the hippocampus. Functional enhancement of cells using CEVA-D (based on exertion of wall shear stress) influences immunomodulatory and paracrine activity, and demonstrates therapeutic potential of resultant MSCs.
Under the terms of a Sponsored Research Agreement with Cellvation, UTHealth is completing remaining development of CEVA-D, including the fabrication of an initial prototype that can deliver a human-sized dose of transduced cells. Preliminary results of cells mechano-transduced with CEVA-D show upregulation of anti-inflammatory potential, consistent with earlier findings using smaller-scale bioreactor prototypes. We are now using the initial prototype to produce robust in vivo data on anti-inflammatory effects of the transduced cells in experimental mouse models (i.e., to show that the cells have a therapeutic effect on injury in vivo). These data will complement previously-generated (primarily in vitro) data that demonstrate the effect of mechanotransduction on the cells.
We expect to file a first IND for CEVA-102 (cells mechano-transduced using CEVA-D) by the first half of 2019.