Autocrine Fibroblast Growth Factor 2 Increases the Multipotentiality of Human Adipose-Derived Mesenchymal Stem Cells

Abstract

Multipotent mesenchymal stem cells (MSCs), first identified in the bone marrow, have subsequently been found in many other tissues, including fat, cartilage, muscle, and bone. Adipose tissue has been identified as an alternative to bone marrow as a source for the isolation of MSCs, as it is neither limited in volume nor as invasive in the harvesting. This study compares the multipotentiality of bone marrow-derived mesenchymal stem cells (BMSCs) with that of adiposederived mesenchymal stem cells (AMSCs) from 12 age-and sex-matched donors. Phenotypically, the cells are very similar, with only three surface markers, CD106, CD146, and HLA-ABC, differentially expressed in the BMSCs. Although colony-forming units-fibroblastic numbers in BMSCs were higher than in AMSCs, the expression of multiple stem cell-related genes, like that of fibroblast growth factor 2 (FGF2), the Wnt pathway effectors FRAT1 and frizzled 1, and other self-renewal markers, was greater in AMSCs. Furthermore, AMSCs displayed enhanced osteogenic and adipogenic potential, whereas BMSCs formed chondrocytes more readily than AMSCs. However, by removing the effects of proliferation from the experiment, AMSCs no longer out-performed BMSCs in their ability to undergo osteogenic and adipogenic differentiation. Inhibition of the FGF2/fibroblast growth factor receptor 1 signaling pathway demonstrated that FGF2 is required for the proliferation of both AMSCs and BMSCs, yet blocking FGF2 signaling had no direct effect on osteogenic differentiation. STEM CELLS

Heparan Sulfate Enhances the Self-Renewal and Therapeutic Potential of Mesenchymal Stem Cells from Human Adult Bone Marrow

“…Unprocessed human bone marrow withdrawn from bilateral punctures of the posterior iliac crest of the pelvic bone of 3 normal volunteers aged 18-45 years (1M-125; Lonza) was separately subjected to Ficoll gradient separation to isolate hMSCs and to eliminate unwanted cell types. Cells were then plated and cultured as previously reported [30].…”

“…Flow cytometric analysis was conducted to compare the profiles of HS-2-expanded and control-expanded hMSCs for CD49a, CD73 (BD Bioscience), CD105 (eBioscience), and STRO-1 (R&D Systems), or isotype-matched controls as previously reported [30,37]. Samples were analyzed using a Guava principal component analysis (PCA-96) bench top flow cytometer and Guava Express Software (Millipore).…”

Differential effects of hypoxia on osteochondrogenic potential of human adipose-derived stem cells

“…Adipose tissue is abundant in the organism and easy to harvest (9,43,44). Moreover, human adipose tissue-derived stem cells (hATSC) have demonstrated their ability to differentiate toward the adipogenic, myogenic, osteogenic, and chondrogenic lineages (7,35,41). hATSC express typical cell surface markers such as CD29, CD44, CD90, and CD105 and lack CD34 and CD45 (8).…”

Bioreactor Strategy in Bone Tissue Engineering: Pre-Culture and Osteogenic Differentiation Under Two Flow Configurations

“…6 Autocrine FGF-2 is known to promote hMSC proliferation and increase their multi-potentiality. 37 Thus, the higher level of FGF-2 in the PC P constructs may also play a role in potentiating hMSC osteogenic differentiation in tandem to ECM proteins. The exact contribution of ECM proteins and endogenous GFs such as FGF-2 requires further study.…”