Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates.

Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates. Biomaterials. 2020 Aug 13;259:120265 Authors: Park J, Lee NG, Oh M, Song J, Kim W, Kwon MG, Kim SG, Han BS, Bae KH, Lee DG, Lee SH, Park JG, Kim JH, Lee J, Min JK Abstract The self-renewal properties of human pluripotent stem cells (hPSCs) contribute to their efficacy in tissue regeneration applications yet increase the likelihood of teratoma formation, thereby limiting their clinical utility. To address this issue, we developed a tool to specifically target and neutralize undifferentiated hPSCs, thereby minimizing tumorigenicity risk without negatively affecting regenerated and somatic tissues. Specifically, we conjugated a monoclonal antibody (K6-1) previously generated in our laboratory against desmoglein 2 (Dsg2), which is highly differentially expressed in undifferentiated hPSCs versus somatic tissues, to the chemotherapeutic agent doxorubicin (DOX). The K6-1-DOX conjugates were selectively targeted and incorporated into Dsg2-positive hPSCs, leading to pH-dependent endosomal release and nuclear localization of DOX with subsequent cytotoxicity via an apoptotic caspase cascade. Conversely, Dsg2-negative fibroblasts showed minimal conjugate uptake or cytotoxicity, suggesting that K6-1-DOX treatment would yield few side effects owing to off-target effects. Selective removal of undifferentiated stem cells was also supported by in vivo ...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research