Adipose‐derived stem cell spheroids are superior to single‐cell suspensions to improve fat autograft long‐term survival

Abstract

Autologous fat transplantation is a widely used procedure for surgical reconstruction of tissues. The resorption rate of this transplantation remains high and unpredictable, reinforcing the need of adjuvant treatments that increase the long‐term stability of grafts. Adipose‐derived stem cells (ASC) introduced as single cells in fat has been shown clinically to reduce the resorption of fat grafts. On the other hand, the formulation of ASC into cell spheroids results in the enhancement of their regenerative potential. In this study, we developed a novel method to produce highly homogeneous ASC spheroids and characterized their features and efficacy on fat transplantation. Spheroids conserved ASC markers and multipotency. A regenerative gene expression profile was maintained, and genes linked to autophagy were upregulated whereas proliferation was decreased. Their secreted proteome was enriched in comparison with single‐cell ASC suspension. Addition of spheroids to fat graft in an animal model of transplantation resulted in a better graft long‐term stability when compared to single ASC suspension. In conclusion, we provide a novel method to manufacture homogenous ASC spheroids. These ASC spheroids are superior to ASC in single‐cell suspension to improve the stability of fat transplants, reinforcing their potential in reconstructive surgery.

Cancer Spheroids and Organoids as Novel Tools for Research and Therapy: State of the Art and Challenges to Guide Precision Medicine

“…These include spinner flasks and bioreactors to increase “flow” in the culture system and microfluidics-based platforms for efficient nutrient diffusion, oxygenation, and waste metabolite disposal. It is also interesting to see the evolution of permeable membranes such as the Transwell ® (Merckmillipore, 0.4 µm) permeable supports and other semi-permeable membrane materials being integrated into perfusion systems and 3D bioprinting techniques to improve nourishment to the organoid during maturation [ 64 , 121 ]. These technologies have helped to increase the lifespan and utility of organoids to months.…”

“…The method was used to generate and cultivate ovarian cancer spheroids using the OVCAR-8 cell line, resulting in spheroids that mimic the structure and cellular distribution of solid tumors. Microwell-based methods are limited by the fact that cells are clustered and cultured in a submerged medium, which can limit oxygen diffusion and lead to hypoxia and cell death, making it difficult to maintain high cell viability [ 117 , 121 ].…”

Adipose-Derived Stromal Cells for Chronic Wounds: Scientific Evidence and Roadmap Toward Clinical Practice

“…However, the latter route of administration is not optimal because it relies on multiple and painful injection sites that cannot be adequately controlled spatially. A few studies showed that clusterization into spheroids enhanced the therapeutic effects of ASC, 36 , 37 fostering wound closure and increasing their engraftment with less cell apoptosis. Some authors introduced ASC spheroids on adhesive films directly covering the ulcer.…”

Synthesis and cytotoxicity studies of Cu(i) and Ag(i) complexes based on sterically hindered β-diketonates with different degrees of fluorination

“…On the other hand, 3D cell cultures are much more effective in closely mimicking the heterogeneity and complexity of the tumor mass, and therefore are more predictive for in vivo results than conventional 2D cell cultures. 115 On these bases, we tested the activity of the newly developed complexes on spheroids obtained from human HCT-15 tumor cells. HCT15 cells are known for their ability to form spheroids, which makes them a valuable tool for studying the interactions between cancer cells and the surrounding microenvironment.…”