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BACKGROUND: De novo adipose regeneration induced by small extracellular vesicles has become a promising method for repairing soft tissue defects. However, due to different animal models and small extracellular vesicle application dosages, it is difficult to quantitatively compare the therapeutic effect of small extracellular vesicles from various sources on adipose regeneration. OBJECTIVE: To compare the regenerative effects of small extracellular vesicles derived from stem cells and small extracellular vesicles from tissue. METHODS: Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation. The particle number, particle size, morphology, and protein expression of small extracellular vesicles were identified by nanoparticle tracking analysis, transmission electron microscopy and western blot assay. A quantitative and evaluative subcutaneous model for adipose regeneration in C57 mice was established using a customized silicone tube. The regenerative effects of induced de novo adipose were compared by cell counting and hematoxylin-eosin staining. RESULTS AND CONCLUSION: (1) Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation. Both small extracellular vesicles were round-shape in transmission electron microscopy with particle size between 50-200 nm, and abundant with the small extracellular vesicles marker protein CD81, CD63 and TSG101. (2) An equal number of small extracellular vesicles were mixed with matrigel in customized silicone tubes, implanted subcutaneously in the back of mice to establish a cell-free and quantifiable adipose regeneration model. (3) On days 3 and 7 after implantation, the results of cell counting and hematoxylin-eosin staining showed that both small extracellular vesicle groups recruited more host cells than the blank group, and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group. (4) 4 weeks after implantation, hematoxylin-eosin staining of the contents in silicone tubes showed that small extracellular vesicles induced de novo adipose regeneration in vivo, and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group. The above results indicated that small extracellular vesicles derived from tissues have a superior effect on inducing de novo adipose regeneration compared to small extracellular vesicles derived from stem cells. [ABSTRACT FROM AUTHOR]

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