The performance of decellularized adipose tissue microcarriers as an inductive substrate for human adipose-derived stem cells

Abstract

With the aim of developing a clinically-translatable cell expansion and delivery vehicle for adipose tissue engineering, the adipogenic differentiation of human adipose-derived stem cells (ASCs) was investigated on microcarriers fabricated from human decellularized adipose tissue (DAT). ASCs seeded on the DAT microcarriers and cultured in adipogenic differentiation medium within a low-shear spinner culture system demonstrated high levels of adipogenic differentiation, as measured by the expression of adipogenic genes, glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, and intracellular lipid accumulation. In contrast, gelatin microcarrier controls did not demonstrate significant adipogenesis, emphasizing the role of the native matrix in mediating ASC differentiation. Interestingly, ASCs cultured on the DAT microcarriers in proliferation medium expressed elevated levels of the adipogenic markers, suggesting that the DAT provided an adipo-inductive substrate for the human ASCs. In vivo testing of the DAT and gelatin microcarriers in a subcutaneous Wistar rat model confirmed injectability and demonstrated stable volume retention over 28 days. Under histological analysis, the DAT microcarriers demonstrated no evidence of immunogenicity or cytotoxicity, with the DAT supporting cellular infiltration and tissue remodeling. Pre-seeding the DAT microcarriers with allogenic rat ASCs enhanced cellularity and angiogenesis within the implant region.