Human Dedifferentiated Adipocytes Show Similar Properties to Bone Marrow‐Derived Mesenchymal Stem Cells

Abstract

Mature adipocytes are generally considered terminally differentiated because they have lost their proliferative abilities. Here, we studied the gene expression and functional properties of mature adipocytes isolated from human omental and subcutaneous fat tissues. We also focused on dedifferentiated adipocytes in culture and their morphologies and functional changes with respect to mature adipocytes, stromal-vascular fraction (SVF)-derived mesenchymal stem cells (MSCs) and bone marrow (BM)-derived MSCs. Isolated mature adipocytes expressed stem cell and reprogramming genes. They replicated in culture after assuming a fibroblast-like shape and expanded similarly to SVF-and BM-derived MSCs. During the dedifferentiation process, mature adipocytes lost their lineage gene expression profile, assumed the typical mesenchymal morphology and immunophenotype, expressed stem cell genes and differentiated into multilineage cells.Moreover, during the dedifferentiation process, we showed changes in the epigenetic status of mature adipocytes, which led dedifferentiated adipocytes to display a similar DNA methylation condition to BM-derived MSCs. Like SVF-and BM-derived MSCs, dedifferentiated adipocytes were able to inhibit the proliferation of stimulated lymphocytes in coculture while mature adipocytes stimulated their growth. Furthermore, dedifferentiated adipocytes maintained the survival and complete differentiation characteristic of hematopoietic stem cells. This is the first study that in addition to characterizing isolated and dedifferentiated adipocytes also reports on the immunoregulatory and hematopoietic supporting functions of these cells. This structural and functional characterization might have clinical applications of both mature and dedifferentiated adipocytes in such fields, as regenerative medicine. STEM CELLS 2012;30:965-974 Disclosure of potential conflicts of interest is found at the end of this article.

Manual Isolation of Adipose-derived Stem Cells from Human Lipoaspirates

“…The pellet itself may have two distinct layers: an upper layer of RBCs and a lower white SVF pellet, containing the ASCs. This protocol recommends the careful aspiration of the oil and adipocytes, as the oil may be toxic to the cell culture and adipocytes have been shown to be capable of dedifferentiation back to a more primitive cell type 32 . However, these adipocytes may be harvested at this point if desired.…”

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…In addition, DFAT cells express OCT4, Sox2, c-myc, Nanog, SSEA1, and telomerase activity like ASCs, but again at higher purity levels [397]. The immunosuppressive capacity of ASCs appears to be retained in DFAT cells as they can suppress the proliferation of cocultured lymphocytes [398]. When examined for their differentiation potentials in vitro, DFAT cells exhibit differentiation similar to their ASC counterparts.…”

Dedifferentiated fat cells: A cell source for regenerative medicine

“…Interestingly, lineage tracing in mice suggest that part of the stromal cells may be derived from adipocytes in vivo [47] , suggesting that ASCs and DFAT cells in part have the same precursor cells. The DFAT cells, however, constitute a more homogeneous cell population than the ASCs, further supporting a role of the mature adipocyte fraction as a source of stem cells [48][49][50] .…”