Mitochondria transplanted adipose-derived stem cells/decellularized adipose tissue hydrogel for adipose tissue regeneration.

Adipose tissue reconstruction is of significant importance for both cosmetic procedures and therapeutic interventions. Current clinical strategies, including autologous adipose tissue grafting and the application of synthetic materials, still have limitations. Decellularized adipose tissue (DAT) hydrogel in combination with adipose-derived stem cells (ADSCs), has emerged as a superior alternative, because of the abundant sources and inherent adipose regeneration capacity. Nevertheless, the therapeutic potential is constrained by the suboptimal functionality of ADSCs, due to the donor health status, long-term culture, and the post-transplantation environment in vivo. Mitochondria transplantation can enhance the proliferation, migration, differentiation, and pro-angiogenic ability of mesenchymal stem cells, thereby improving the tissue regeneration outcomes. In our research, we developed a novel soft tissue filler, mitochondria transplanted adipose-derived stem cells/decellularized adipose tissue (Mito-ADSCs/DAT) hydrogel. The constructive influence of the Mito-ADSCs/DAT hydrogel to angiogenesis and adipose tissue regeneration was validated in the nude mouse subcutaneous injection model. In vitro experiments and RNA-seq analysis were employed to elucidate the mechanism of Mito-ADSCs in improving adipose tissue regeneration. Although no significant enhancement in adipogenic differentiation was observed in vitro, the Mito-ADSCs exhibited promoted maximal respiration and spare respiratory capacity, and the glycolysis metabolism in Mito-ADSCs increased. Moreover, Mito-ADSCs demonstrated a marked increase in pro-angiogenic capability, which was corroborated by both in vitro assays and RNA-seq analysis. In general, our research demonstrated that the Mito-ADSCs/DAT hydrogel achieved ideal results in adipose tissue regeneration, emerging as a promising soft tissue filler for adipose tissue reconstruction and warranting further investigation for clinical translation.