The Biomolecular Basis of Adipogenic Differentiation of Adipose-Derived Stem Cells

Abstract

There is considerable attention regarding the role of receptor signaling and downstream-regulated mediators in the homeostasis of adipocytes, but less information is available concerning adipose-derived stem cell (ASC) biology. Recent studies revealed that the pathways regulating ASC differentiation involve the activity of receptor tyrosine kinases (RTKs), including fibroblast growth factor, vascular endothelial growth factor, ErbB receptors and the downstream-regulated serine/threonine protein kinase B (Akt) and phosphatase and tensin homolog (PTEN) activity. RTKs are cell surface receptors that represent key regulators of cellular homeostasis but also play a critical role in the progression of cancer. Many of the metabolic effects and other consequences of activated RTKs are mediated by the modulation of Akt and extracellular signal-regulated protein kinases 1 (Erk-1) signaling. Akt activity sustains survival and the adipogenic differentiation of ASCs, whereas Erk-1 appears downregulated. The inhibition of FGFR-1, EGFR and ErbB2 reduced proliferation, but only FGFR-1 inihibition reduced Akt activity and adipogenesis. Adipogenesis and neovascularization are also chronologically and spatially coupled processes and RTK activation and downstream targets are also involved in ASC-mediated angiogenesis. The potentiality of ASCs and the possibility to modulate specific molecular pathways underlying ASC biological processes and, in particular, those shared with cancer cells, offer new exciting strategies in the field of regenerative medicine.

Platelet-Rich Plasma Influences Expansion and Paracrine Function of Adipose-Derived Stromal Cells in a Dose-Dependent Fashion

“…Adipose-derived stromal cells cultured in media with platelet-rich plasma maintain their capability to differentiate into adipocytes. [45][46][47] Differentiation of adipose-derived stromal cells into adipocytes could significantly contribute to end graft volume, as suggested by Kølle et al…”

Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis

“…In order to form substantial adipose tissue, mesenchymal progenitor cell subpopulations must undergo clonal expansion prior to differentiating into mature adipocytes[36, 37, 68]. ERK1,2 kinases are required for expansion and loss of ERK1 expression results in lean mice[36].…”

“…ERK1,2 kinases are required for expansion and loss of ERK1 expression results in lean mice[36]. However, this MAP kinase plays complex roles in adipogenesis since sustained activity blocks adipocyte maturation and promotes insulin resistance [36, 37, 69, 70]. RHAMM expression has previously been reported to be high in dormant stem cells but is down-regulated during embryonic stem cell differentiation suggesting that lowering RHAMM levels, which affect ERK1,2 activity, may be an important step in initiating differentiation of a variety of stem cells [33, 71, 72].…”

“…Extracellular RHAMM:HA fragment interactions activate key adipogenic regulators such as MAP kinases (e.g. ERK1) [36, 37] while intracellular RHAMM partners with and regulates ERK1 activity and subcellular distribution[38]. Intracellular RHAMM also partners with ANKRYN26, a protein that suppresses adipogenesis[36, 39].…”

Characterization of Chondrogenic Gene Expression and Cartilage Phenotype Differentiation in Human Breast Adipose-Derived Stem Cells Promoted by Ginsenoside Rg1 In Vitro

“…It is simple to expand ASCs to large numbers in vitro compared with bone marrow-derived mesenchymal stromal cells (BMSCs) [14], and there is less cell heterogeneity in ASCs than BMSCs due to the mixture of hematopoietic and mesenchymal stem cells [15][16][17]. Similar to BMSCs, various studies have described the plasticity of ASCs to differentiate towards chondrocytes, osteoblasts, adipocytes, myocytes (cardiomyocytes, smooth muscle, and skeletal muscle cells) and neural phenotype cells in different inductive culture systems [18][19][20][21][22]. Although BMSCs are considered to be a valuable source for bone tissue regeneration in human diseases, the capacity of autologous BMSCs to differentiate toward functional bone-forming osteoblasts remains relatively limited for bone regeneration in vivo [23].…”