Autocrine FGF2 Increases the Multipotentiality of Human Adipose-Derived Mesenchymal Stem Cells

¹ Laboratory of Stem Cells and Tissue Repair, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Proteos, Singapore 138673
² Division of Bioengineering, Faculty of Engineering, Engineering Drive 1, National University of Singapore, Singapore 119260
³ Division of Bioengineering, Faculty of Engineering, Engineering Drive 1, National University of Singapore, Singapore 119260.; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074
⁴ Laboratory of Stem Cells and Tissue Repair, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Proteos, Singapore 138673.; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074

^* To whom correspondence should be addressed. E-mail: scool{at}imcb.a-star.edu.sg.

	Abstract

Multipotent mesenchymal 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 source to bone marrow for the isolation of MSCs, as it is neither limited in volume nor as invasive in the harvesting. This study compares the multipotentiality of MSCs from either bone marrow (BMSCs) or adipose-derived (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 CFU-F numbers in BMSCs were higher than in AMSCs, the expression of multiple stem cell-related genes, together with increased expression of FGF2, the Wnt pathway effectors FRAT1 and frizzled 1 and other self-renewal markers were 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/FGFR1 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.