Selenium-Containing Copolypeptides Enhance Cryopreservation of Mesenchymal Stem Cells

Abstract Bioinspired polypeptides attract much attention as promising macromolecular cryoprotectants owing to their capacity to mimic ice-regulating functions of natural antifreeze proteins. Advances in synthetic methodologies have enabled tailored incorporation of functional moieties in polypeptides. Herein, a series of random copolypeptides (SeMmEn) composed of l-selenomethionine and l-glutamic acid are synthesized, which exhibit ice-controlling properties and H2O2-scavenging antioxidant activities. Polypeptide complex coacervates are further prepared by mixing SeM15E15 with cationic ε-poly-l-lysine, displaying stability under physiological conditions. In the serum-free cryopreservation of rat bone marrow mesenchymal stem cells, the cytocompatible SeM15E15-based coacervate achieves high post-thaw cell survival, as comparable with the 10% v/v dimethyl sulfoxide (DMSO) control. Post-thaw cells maintain normal proliferative activity and intact cellular integrity with osteogenic and adipogenic differentiation potentials. This work reduces the DMSO dosage during cell cryopreservation and represents the feasibility of employing selenium-containing polypeptide coacervates to improve the cryopreservation of mesenchymal stem cells.