Dedifferentiated fat cells: A cell source for regenerative medicine

Abstract

The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipidfree multipotent cells, referred to as dedifferentiated fat (DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo , the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.

hASC and DFAT, Multipotent Stem Cells for Regenerative Medicine: A Comparison of Their Potential Differentiation In Vitro

“…The cells obtained from mature adipocytes and maintained in “ceiling mode” start a gradual process of dedifferentiation, highlighted by positive markers of mesenchymal stem cells [ 28 , 34 ]. This dedifferentiation process was also observed in other cells (i.e., chondrocytes and smooth muscle cells) and seems to be induced by the hypoxia that occurs during the “ceiling cultures” [ 35 , 36 , 37 ]. The mechanisms that induce the dedifferentiation process of mature fat cells and the specific surface markers of DFAT populations must be studied more thoroughly.…”

“…hASCs and DFAT in vitro showed similar proliferative capacity (expressed as the generation time obtained from the respective growth curves). By adding appropriate factors to the culture medium DFAT, hASC and BM-MSC cells can be induced to differentiate into osteoblastic, adipogenetic, and chondroblastic lineages [ 37 , 38 , 39 ]. All the evaluated differentiation parameters were positive for the presence of acidic mucopolysaccharides: alkaline phosphatase, calcium deposits, and the intracytoplasmic accumulation of lipid droplets.…”

Insulin negatively regulates dedifferentiation of mouse adipocytes in vitro

“…The phenomena of cell differentiation, dedifferentiation and reprogramming are the basis of tissue repair and regeneration [18][19][20]. However, the triggers and regulatory mechanisms of adipocyte dedifferentiation remain unclear, even though the phenomenon of adipocyte dedifferentiation has been reported earlier [1,[21][22][23][24].…”

Human adult pluripotency: Facts and questions

“…Adipose tissue was one of the first sources reported for generating MUSE cells and another reportedly pluripotent adult human cell source is dedifferentiated adipose-derived cells (DFATs). Mature adipocytes isolated from adult human adipose tissue that are subjected to an in vitro dedifferentiation strategy (ceiling culture) revert to a more primitive phenotype and gain proliferative and differentiative abilities[35]. Indeed, DFATs were found to have triploblastic differentiation potential in vitro and do not generate teratomas when injected in immuno-deficient mice[36].…”