Resources
Authors & Affiliations
Nora Hanna Rentsch, Beatriz Achón Buil, Rebecca Z. Weber, Jana Sievers-Liebschner, Petra B. Welzel, Ruslan Rust, Christian Tackenberg
Abstract
Every three seconds, someone suffers a stroke, a major contributor to global mortality and disability. Stroke survivors often face limited treatment options and significant disabilities. Stem cell therapy holds promise for brain regeneration and functional recovery, yet it's hindered by poor graft survival post-transplantation due to the hostile stroke environment. Our goal is to enhance graft survival and regenerative potential through cell acclimatization using sublethal hypoxic preconditioning or functionalized, compressible cryogel microcarriers. A protocol for obtaining injectable cryogel particles from a scaffold as well as successful handling together with our iPSC-derived neural progenitor cell (NPC) line was established. Among various adhesion ligands tested, cyclic RGD emerged as the most effective for cell-cryogel interaction. Furthermore, cryogels can be functionalized with pro-survival and pro-angiogenic factors that are released to mitigate the hostile microenvironment. Studies on the release kinetics of FGF and VEGF have shown a steady release over two weeks, with an initial burst on the first day. Adjusting of heparin and growth factor concentrations is needed to fine-tune the release rate. Initial findings suggest promising NPC-cryogel interactions that improve cell survival. Following comprehensive in vitro characterization, NPCs loaded onto cryogel microcarriers will be transplanted into a stroke mouse model for longitudinal graft survival assessment. Our research aims to enhance stroke therapy outcomes by overcoming graft survival challenges and promoting brain regeneration.