The combination of DHEA, histamine, and insulin increases adipogenic differentiation and enhances tissue transplantation outcome in mice

Abstract

Adipose stem cells (ASCs) are pluripotent cells that can generate pure fat tissue for regeneration. Differentiated adipose cells have been generated by a common inducer cocktail composed of dexamethasone, insulin, and isobutylmethylxanthine (DIM). The major drawbacks of adipose cells are their tendency to float on the culture media and their cost. To overcome some of these disadvantages, a new inducer cocktail that includes insulin, dehydroepiandrosterone, and histamine (DHIH) was tested. As a result, lipid accumulation was elevated more than twofold with DHIH than with DIM. Cell adhesion and viability, which are important factors for stable differentiation, were increased with DHIH and were proven through measurement of mRNA expression levels of adhesion marker genes, N-cadherin and vascular cell adhesion molecule, as well as through an alamar blue assay. The expression of adipogenesis-related genes, adiponectin, and glucose transporter type 4 lasted for a long time. To improve the efficiency of grafting, cell adhesion and neovascularization need to be increased. Neovascularization was observed around the transplanted adipose cells, which showed a higher number of vessel formation in DHIH than in DIM. The above results suggest that DHIH can produce pure differentiated adipose cells effectively and enhance their adhesion onto the target location when these differentiated adipose cells were applied as a clinical resource.