Nanomedicine-enhanced SCAP hybrid spheroids: A novel approach for improved stem cell survival.

In regenerative medicine, the therapeutic potential of mesenchymal stem cells (MSC), such as stem cells from human apical papilla (SCAP), is well-documented and largely attributed to their secretome. However, their poor survival post-transplantation limits their efficacy. This study hypothesized that combining SCAP spheroids with nanomedicines loaded with NecroX-5 (an anti-necrotic drug) and rapamycin (an immunosuppressive agent) would enhance SCAP survival in vivo. The approach aimed to reduce oxidative stress-related cell death and suppress immune reactions towards xeno-/allogenic cells. Two types of nanocarriers, polymeric nanoparticles (NP) and lipid nanocapsules (LNC), were compared to encapsulate NecroX-5 and rapamycin. A magnetic-dependent method was employed to associate SCAP with nanomedicines, involving co-encapsulation of drugs and Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) in the nanocarriers and cell magnetization using Nanoshuttle™. In vivo, SCAP hybrid spheroids expressing Luciferase, when injected subcutaneously into immunocompetent mice, showed increased bioluminescence signals compared to regular spheroids. These results provide proof-of-concept that magnetic-driven association of cells and nanomedicines into hybrid spheroids is feasible and suggest that delivering SCAP as hybrid spheroids can enhance their survival.