부산대학교 도서관

The efficacy of cell therapy is limited by low retention and survival of transplanted cells in the target tissues. In this work, we hypothesize that pharmacological preconditioning with celastrol, a natural potent antioxidant, could improve the viability and functions of mesenchymal stromal cells (MSC) encapsulated within an injectable scaffold. Bone marrow MSCs from rat (rMSC) and human (hMSC) origin were preconditioned for 1 hour with celastrol 1 μM or vehicle (DMSO 0.1% v/v), then encapsulated within a chitosan-based thermosensitive hydrogel. Cell viability was compared by alamarBlue and live/dead assay. Paracrine function was studied first by quantifying the proangiogenic growth factors released, followed by assessing scratched HUVEC culture wound closure velocity and proliferation of HUVEC when cocultured with encapsulated hMSC. In vivo, the proangiogenic activity was studied by evaluating the neovessel density around the subcutaneously injected hydrogel after one week in rats. Preconditioning strongly enhanced the viability of rMSC and hMSC compared to vehicle-treated cells, with 90% and 75% survival versus 36% and 58% survival, respectively, after 7 days in complete media and 80% versus 64% survival for hMSC after 4 days in low serum media (p