The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes.

Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a special group of multipotent cells. However, their phenotype and cellular nature remain unclear. Our study found that human DFAT cells adopted perivascular characteristics and behaviors. Flow cytometry and immunofluorescent staining revealed that human DFAT cells positively expressed markers highly related to perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT cells displayed vascular network formation ability in Matrigel, and they noticeably promoted and stabilized the vessel structures formed by human umbilical vascular endothelial cells (HUVECs) in vitro. These results provide novel evidence on the pericyte nature of human DFAT cells, further supporting the recent model for the perivascular origin of adult stem cells, in which tissue-specific progenitor cells in mesenchymal tissues associate with blood vessels, exhibiting perivascular characteristics and functions.

Application of dedifferentiated fat cells for periodontal tissue regeneration.

Periodontal diseases result from inflammation by bacterial infection in plaques, leading to tooth loss. However, regenerative approaches with periodontal tissue regeneration by guided tissue regeneration and enamel matrix derivative are not yet well established. Tissue regeneration requires three factors: cells, scaffold, and growth factors. Dedifferentiated fat cells (DFATs) are pluripotent with the same differentiation capacities as mesenchymal stem cells (MSCs). Access to MSCs is limited, whereas donor cells for DFATs are abundant in adipose tissues and can be non-invasively obtained. Therefore, we tested DFATs as a new source for periodontal tissue regeneration in an experimental periodontal tissue loss model in rats by transplanting DFATs on an atelocollagen scaffold using DFATs isolated from Sprague-Dawley (SD) rats expressing green fluorescent protein (GFP). GFP-DFAT cells were transplanted on the palatal side of the upper left first molar in SD rats and detected by H&E staining, GFP, and proliferating cell nuclear antigen (PCNA) expression. DFAT differentiation was also evaluated in three-dimensional cultures. GFP positive cells were detected in the regenerated tissue by the DFATs/scaffold mixture at 4 weeks after transplantation, and PCNA-positive cells were significantly increased in the periodontal ligament along the new bone in the DFATs/scaffold group more than in the scaffold-only group, suggesting that DFATs differentiate in the same manner as MSCs and regenerate in the defective areas. Consistent with previous reports, DFATs differentiation was slower than that with stem cells. The present study demonstrates that DFATs are pluripotent and an effective new source of cells for periodontal tissue regeneration.

Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues.

When adipose-derived stem cells (ASCs) are retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dedifferentiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. DFAT cells re-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells are introduced and the current profiles of their cellular nature are summarized. Under proper induction culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenic and myogenic potentials. In angiogenic conditions, DFAT cells could exhibit perivascular characteristics and elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine.