Effects of mature adipocyte-derived dedifferentiated fat (DFAT) cells on generation and vascularisation of dermis-like tissue after artificial dermis grafting

Abstract

Although artificial dermis (AD) is effective for skin reconstruction, it requires two separate procedures, because the AD must be vascularised before skin grafts. To shorten the period of the dermis-like tissue generation before the secondary skin grafting must be beneficial. Dedifferentiated fat (DFAT) cells are isolated from mature adipose cell suspensions and have potential to differentiate into multiple cell types including endothelial cells. This study aimed to investigate effects of DFAT cells on dermal regeneration after AD grafts in rats. The effects of combination use of DFAT cells and basic fibroblast growth factor (bFGF) were also tested to mimic clinical situations. DFAT cells were isolated from SD rats. Full-thickness wounds were created on the back of rats followed by AD grafting. Five groups were established; Group I: control, Group II: treated with DFAT cells, Group III: treated with bFGF, Group IV: treated with both of DFAT cells and bFGF, and Group V: treated with Green fluorescent protein (GFP)-labelled DFAT cells and bFGF. Histological evaluation was serially performed. Group IV showed markedly promoted vascularisation of dermis-like tissue. In particular, capillary infiltration into the dermis was obtained within 2 days. Immunohistochemical examination revealed that the transplanted DFAT cells had differentiated into endothelial cells and participated in angiogenesis. Group IV also showed a marked increase in the thickness of the dermis like tissue. The present results suggest that the use of DFAT cells under bFGF treatment could be beneficial to shorten the period required for dermal regeneration and vascularisation and contribute to use AD more effectively and safely.

Dedifferentiated fat cells in polyglycolic acid-collagen nerve conduits promote rat facial nerve regeneration

“…DFAT cells can transdifferentiate not only into cells, which are identified to those derived from the paraxial mesoderm, but also into vascular endothelial cells, vascular smooth muscle cells, and myocardial cells derived from the splanchnic mesoderm [10]. Furthermore, the transplantation of DFAT cells into injured areas is found to result in a wide range of tissue repair and beneficial effects; improved blood flow in a lower-limb ischemia model, improved heart function in a myocardial infarction model, improved urination in a spinal cord injury model [11], improved kidney function effect in a chronic kidney disorder model [12], improved urination in a urethral sphincter disorder model [13], increased bone density in an osteoporosis model [14], and the promotion of skin regeneration after artificial dermal transplantation in a full-thickness skin defect model [15]. Because DFAT cells are prepared from the mature adipocyte fraction during the fractionation of mature adipocytes, highly pure cells can be obtained without complicated selection procedures, and the volume of tissue sample required is approximately 1 g or less [16].…”

Promising recent regenerative medicine applications in plastic and reconstructive surgery

“…Mesenchymal adipose and endothelial stem cells are believed to be the main contributors to the various effects of fat grafting, including improved contour, quality of skin, and neovascularization [1,[24][25][26][27][28][29]. The fat stem cells are highly proliferative and believed to be progenitors to variety of soft tissue, including osteoblasts, chondrocytes, myocytes, epithelial cells and neuronal cells.…”

Effects of combination therapy using basic fibroblast growth factor and mature adipocyte-derived dedifferentiated fat (DFAT) cells on skin graft revascularisation

“…In an earlier study, we investigated the effect of combined use of bFGF and mature adipocytederived dedifferentiated fat (DFAT) cells on generation and vascularisation of dermis-like tissue after artificial dermis grafting [27]. The combination therapy showed a significantly greater angiogenic effect compared with bFGF monotherapy.…”