Development of Hetero-Cell Type Spheroids Via Core–Shell Strategy for Enhanced Wound Healing Effect of Human AdiposeDerived Stem Cells

ABSTRACT

BACKGROUND@#Stem cell-based therapies have been developed to treat various types of wounds. Human adiposederived stem cells (hADSCs) are used to treat skin wounds owing to their outstanding angiogenic potential. Although recent studies have suggested that stem cell spheroids may help wound healing, their cell viability and retention rate in the wound area require improvement to enhance their therapeutic efficacy. @*METHODS@#We developed a core–shell structured spheroid with hADSCs in the core and human dermal fibroblasts (hDFs) in the outer part of the spheroid. The core–shell structure was formed by continuous centrifugation and spheroid incubation. After optimizing the method for inducing uniform-sized core–shell spheroids, cell viability, cell proliferation, migration, and therapeutic efficacy were evaluated and compared to those of conventional spheroids. @*RESULTS@#Cell proliferation, migration, and involucrin expression were evaluated in keratinocytes. Tubular assays in human umbilical vein endothelial cells were used to confirm the improved skin regeneration and angiogenic efficacy of core–shell spheroids. Core–shell spheroids exhibited exceptional cell viability under hypoxic cell culture conditions that mimicked the microenvironment of the wound area. @*CONCLUSION@#The improvement in retention rate, survival rate, and angiogenic growth factors secretion from core– shell spheroids may contribute to the increased therapeutic efficacy of stem cell treatment for skin wounds.