Fortifying the angiogenic efficacy of adipose derived stem cell spheroids using spheroid compaction

Transplantation of stem cell spheroids to ischemic tissues has been suggested as an effective method for treating ischemic disease, but its therapeutic efficacy varies according to the preparation methods for spheroids. We hypothesized that increasing cell compaction while preparing spheroids could improve the angiogenic efficacy of spheroids. Optimized human adipose derived stem cell (hADSC) spheroids were shown to upregulate cell adhesion molecule, and angiogenic paracrine factors expression with downregulated senescence and apoptotic markers expression. We noted that the low seeding density (1 x 10(4) cells (10KS)) had a far lower probability of forming spheroids than higher seeding densities (3 x 10(4) cells (30KS) and 1 x 10(5) cells (100KS)). The 30KS spheroids demonstrated higher cell density and expression levels of the angiogenic paracrine factor expression compared to those of 100 KS spheroids. 30KS spheroids with additional incubation (A30KS) showed significantly increased angiogenic paracrine factors and cell adhesion molecule expressions with decreased senescence expression compared to those in 30KS spheroids. Transplanting A30KS spheroids showed significantly enhanced therapeutic angiogenesis in mouse hindlimb ischemia model compared to conventional spheroid transplantation. This study successfully defined a set of novel criteria for spheroid culture, which may contribute to future stem cell therapies. (C) 2020 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.