Mature Adipocyte-Derived Cells, Dedifferentiated Fat Cells (DFAT), Promoted Functional Recovery from Spinal Cord Injury-Induced Motor Dysfunction in Rats

Abstract

Transplantation of mature adipocyte-derived cells (dedifferentiated fat cells) led to marked functional recovery from spinal cord injury (SCI)-induced motor dysfunction in rats. When mature adipocytes were isolated from rat adipose tissue and grown in ceiling culture, transformation into fibroblast-like cells without lipid droplets occurred. These fibroblast-like cells, termed dedifferentiated fat cells (DFAT), could proliferate and could also differentiate back into adipocytes. DFAT expressed neural markers such as nestin, betaIII tubulin, and GFAP. Allografting of DFAT into SCI-induced rats led to significant recovery from hindlimb dysfunction. Grafted cells were detected at the injection site, and some of these cells expressed betaIII tubulin. DFAT expressed neurotrophic factors such as BDNF and GDNF prior to transplantation, and grafted cells were also positive for these factors. Therefore, these neurotrophic factors derived from grafted DFAT might have contributed to the promotion of functional recovery. These findings also suggest that mature adipocytes could become a new source for cell replacement therapy to treat central nervous system disorders.

Human adipose-derived stem cells for the treatment of intracerebral hemorrhage in rats via femoral intravenous injection

“…6 and Fig. 7), as reported previously by others [14,16,18,20,32]. We used the huADSC generated from the fat tissue of a 65-year-old donor to treat ICH inflicted rats and evaluated functional behavior of the rats for 28 days.…”

“…Many studies have indicated that human adipose-derived adult stem cells are a population of mesenchymal stem cells and demonstrated differentiation of stem cells into adipocytes, chondrocytes, myocytes, osteoblasts and neural progenitor cells after chemical inductions [14,16,18,20,32]. Transplantation of matured adipocyte-derived cells and dedifferentiated fat cells to promote functional recovery from spinal cord injury-induced motor dysfunction in rats was reported [20] and an attempt of cellular therapy employing human adipose tissue-derived stromal cells for rats with cerebral ischemia after MCAO resulted in significant functional improvement [17]. We found that the huADSC consist of innate neural stem cells in addition to MSCs based on our observation that the huADSC expressed neural β-III tubulin, nestin, GFAP and MAP2 proteins (Fig.…”

“…Brain edema formation and BBB (blood-brain barrier) disruption, caused by both hematomal and peri-hematomal injuries, have also been reported to be an important component of brain injury after ICH [7][8][9][10][11][12]. Mesenchymal stem cells generated from murine or human adipose tissues have been well documented [13][14][15][16][17][18][19][20][21][22] and have been named as adipose-derived stem cells [14,15,19,20], adipose-derived adult stem cells [21], adipose derived stromal cells [16], adipose derived mesenchymal stem cells [18], adipose tissuederived stem cells [13], and adipose tissue stromal cells [17]. Systemic transplantation of human adipose-derived stem cells to attenuate cerebral inflammation and to facilitate motion recovery of rats from cerebral degeneration induced by ICH has been attempted [23].…”

The Effect of Am-80, a Synthetic Retinoid, on Spinal Cord Injury-Induced Motor Dysfunction in Rats

“…24,38) Cell replacement therapy is currently attracting attention as a potentially attractive strategy for the treatment of neurodegenerative diseases including SCI. Am-80 combined with cell therapy 42) might provide a new strategy for SCI.…”

Generation of Human Adipose Stem Cells through Dedifferentiation of Mature Adipocytes in Ceiling Cultures

“…Exploiting the stem cell capacity of DFAT cells, many groups have investigated their potential to treat or improve various diseases 8,9 . Improvements of pathologic conditions, such as infracted cardiac tissue, spinal cord injury and urethral sphincter dysfunction, have been observed with DFAT cell injections in rat models of disease [10][11][12] .…”