Abstract
The aim of this study was to investigate the characteristics of insulin producing cells (IPCs) differentiated from adipose-tissue derived stem cells (ADSCs) isolated from human subcutaneous and visceral adipose tissues and identify ADSCs suitable for differentiation into efficient and functional IPCs. Subcutaneous and visceral adipose tissues collected from four (4) patients who underwent digestive surgeries at The Tokushima University (000035546) were included in this study. The insulin secretion of the generated IPCs was investigated using surface markers by: fluorescence activated cell sorting (FACS) analysis; cytokine release; proliferation ability of ADSCs; in vitro (glucose-stimulated insulin secretion: (GSIS) test/in vivo (transplantation into streptozotocin-induced diabetic nude mice). The less fat-related inflammatory cytokines secretions were observed (P < 0.05), and the proliferation ability was higher in the subcutaneous ADSCs (P < 0.05). Insulin expression and GISI were higher in the subcutaneous IPCs (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of all mice that received IPCs from subcutaneous fat tissue converted into normo-glycaemia in thirty (30) days post-transplantation (4/4,100%). Transplanted IPCs were stained using anti-insulin and anti-human leukocyte antigen antibodies. The IPCs generated from the ADSCs freshly isolated from the human fat tissue had sufficient insulin secreting ability in vitro and in vivo.
Highlights
When considering the generation and clinical application of IPCs it is important to investigate optimal adipose tissue serving as the cell source
As the location to harvest ADSCs, this study focused on subcutaneous adipose tissue because of the safety and simplicity of procurement
It is reported ADSCs derived from subcutaneous adipose tissue can be regenerated and used by dermatology and in plastic surgery[17,18]
Summary
When considering the generation and clinical application of IPCs it is important to investigate optimal adipose tissue serving as the cell source. This study currently focused on the procurement location of adipose tissue. The adipose tissue accumulates mainly in subcutaneous and visceral locations. It has already been reported that the microenvironments of adipose tissue such as immune-cells and various cytokines www.nature.com/scientificreports/. Secreted from them differ, depending on the location of the adipose tissue[13,14,15,16]. There must be various functional and cell-fatal differences depending on the location of the adipose tissue due to the differences in the microenvironment. In this study IPCs generated from ADSCs isolated from fresh human subcutaneous and visceral adipose tissues were characterized and the identification which ADSCs can achieve to differentiate into more efficient and functional IPCs was shown
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