Effects of Transforming Growth Factor β1 and Dexamethasone on the Growth and Chondrogenic Differentiation of Adipose-Derived Stromal Cells

Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Tissue Engineering (Impact Factor: 4.25). 01/2004; 9(6):1301-12. DOI: 10.1089/10763270360728215
Source: PubMed


The effects of soluble mediators and medium supplements commonly used to induce chondrogenic differentiation in different cell culture systems were investigated to define their dose-response profiles and potentially synergistic effects on the chondrogenic differentiation of adipose-derived adult stromal (ADAS) cells. Human ADAS cells were suspended within alginate beads and cultured in basal medium with insulin, transferrin, and selenious acid (ITS+) or fetal bovine serum (FBS) and treated with different doses and combinations of TGF-beta1 (0, 1, and 10 ng/mL) and dexamethasone (0, 10, and 100 nM). Cell growth and chondrogenic differentiation were assessed by measuring DNA content, protein and proteoglycan synthesis rates, and proteoglycan accumulation. The combination of ITS+ and TGF-beta1 significantly increased cell proliferation. Protein synthesis rates were increased by TGF-beta1 and dexamethasone in the presence of ITS+ or FBS. While TGF-beta1 significantly increased proteoglycan synthesis and accumulation by 1.5- to 2-fold in the presence of FBS, such effects were suppressed by dexamethasone. In summary, the combination of TGF-beta1 and ITS+ stimulated cell growth and synthesis of proteins and proteoglycans by human ADAS cells. The addition of dexamethasone appeared to amplify protein synthesis but had suppressive effects on proteoglycan synthesis and accumulation.

16 Reads
  • Source
    • "These cells are all capable of chondrogenic differentiation in appropriate culture environments [12]. Human adipose-derived stem cells (hADSCs) could represent a viable source of mesenchymal-like stem cells for CTE applications, due to their easy harvest [13] [14], high chondrogenic potential [13] [15] [16], and wound healing properties [17] [18] [19] [20]. Despite significant progress, obtaining from hADSCs functional chondrocytes capable of secreting type II collagen in tridimensional scaffolds remains challenging [21]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cartilage has limited regeneration potential. Thus, there is an imperative need to develop new strategies for cartilage tissue engineering (CTE) amenable for clinical use. RecentCTE approaches rely on optimal cell-scaffold interactions,which require a great deal of optimization. In this studywe attempt to build a novel gelatin- (G-) alginate- (A-) polyacrylamide (PAA) 3D interpenetrating network (IPN) with superior performance in promoting chondrogenesis from human adipose-derived stem cells (hADSCs). We show that our G-A-PAA scaffold is capable of supporting hADSCs proliferation and survival, with no apparent cytotoxic effect. Moreover, we find that after exposure to prochondrogenic conditions a key transcription factor known to induce chondrogenesis, namely, Sox9, is highly expressed in our hADSCs/G-A-PAAbioconstruct, alongwith cartilage specific markers such as collagen type II, CEP68, and COMP extracellular matrix (ECM) components. These data suggest that our G-A-PAA structural properties and formulation might enable hADSCs conversion towards functional chondrocytes.We conclude that our novel G-A-PAA biomatrix is a good candidate for prospective in vivo CTE applications.
    Stem cell International 05/2015; · 2.81 Impact Factor
  • Source
    • "There are two promising cell sources for cartilage tissue engineering: Mesenchymal stem cells (MSCs) and chondrocytes. Both can be differentiated in 3D culture[1112] in the presence of growth factors such as transforming growth factor-β (TGF-β), insulin-like growth factor-1, and bone morphogenic protein-6 (BMP-6).[13] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Platelet-rich plasma (PRP), an autologous derivative of whole blood, has been recently used in surgical treatment. PRP contains growth factors including transforming growth factor-β (TGF-β), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) and also bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article describes the current clinical applications of PRP in chondrogenesis. This study reviews and evaluates the studies that have been published in the field of chondrogenesis. All aspects of using PRP in chondrogenesis are reviewed.
    06/2014; 3(1):138. DOI:10.4103/2277-9175.135156
  • Source
    • "and produce additional adipocyte-specific proteins upon induction [40]. ASCs have the potential to differentiate into bone, cartilage and muscle as well as adipose and neural tissue [41] [42] [43] [44] [45] [46] [47]. This ability to differentiate towards different mesenchymal lineages has stimulated interest in their clinical use. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cartilage tissue engineering (CTE) applications are focused towards the use of implantable biohybrids consisting of biodegradable scaffolds combined with in vitro cultured cells. Hyaluronic acid (HA) and chondroitin sulfate (CS) were identified as the most potent prochondrogenic factors used to design new biomaterials for CTE, while human adipose-derived stem cells (ASCs) were proved to display high chondrogenic potential. In this context, our aim was not only to build novel 3D porous scaffolds based on natural compounds but also to evaluate their in vitro biological performances. Therefore, for prospective CTE, collagen-sericin (Coll-SS) scaffolds improved with HA (5% or 10%) and CS (5% or 10%) were used as temporary physical supports for ASCs and were analyzed in terms of structural, thermal, morphological, and swelling properties and cytotoxic potential. To complete biocompatibility data, ASCs viability and proliferation potential were also assessed. Our studies revealed that Coll-SS hydrogels improved with 10% HA and 5% CS displayed the best biological performances in terms of cell viability, proliferation, morphology, and distribution. Thus, further work will address a novel 3D system including both HA 10% and CS 5% glycoproteins, which will probably be exposed to prochondrogenic conditions in order to assess its potential use in CTE applications.
    11/2013; 2013(4):598056. DOI:10.1155/2013/598056
Show more