FGF‐2 enhances the mitotic and chondrogenic potentials of human adult bone marrow‐derived mesenchymal stem cells

Abstract

Human mesenchymal stem cells (hMSCs) expanded with and without fibroblast growth factor (FGF) supplementation were compared with respect to their proliferation rate, ability to differentiate along the chondrogenic pathway in vitro, and their gene expression profiles. hMSCs expanded in FGF-supplemented medium were smaller and proliferated more rapidly than hMSCs expanded in control conditions. Chondrogenic cultures made with FGF-treated cells were larger and contain more proteoglycan than those made with control cells. Furthermore, aggregates of FGF-treated cells lacked the collagen type I-positive and collagen type II-negative outer layer characteristic of aggregates of control cells. A total of 358 unique transcripts were differentially expressed in FGF-treated hMSCs. Of these, 150 were upregulated and 208 downregulated. Seventeen percent of these genes affect proliferation. Known genes associated with cellular signaling functions comprised the largest percentage ( approximately 20%) of differentially expressed transcripts. Eighty percent of differentially expressed extracellular matrix-related genes were downregulated. The present findings that FGF-2 enhances proliferation and differentiation of hMSCs adds to a growing body of evidence that cytokines modulate the differentiation potential and, perhaps, the multipotentiality of adult stem cells. With the generation of gene expression profiles of FGF-treated and control cells we have taken the first steps in the elucidation of the molecular mechanism(s) behind these phenomena.

Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs

“…This study develops upon previous work to ascertain if such expansion conditions, specifically expansion in the presence of FGF-2, could further enhance the mechanical functionality of cartilaginous constructs engineered using IFP derived MSCs. The observed beneficial effects of expanding in the presence of FGF-2 is consistent with previous findings for other sources of stem cells in terms of more rapid proliferation and improved chondrogenic potential evident by increased levels of matrix synthesis (Solchaga et al 2005;Khan et al 2008;Solchaga et al 2010). After 3 weeks of in vitro culture, IFP derived MSCs expanded in the presence of FGF-2 generated cartilaginous grafts whose mechanical functionality was at least comparable to that which we have previously reported using other cell types from the same species at the same time point (Thorpe et al 2008;Buckley et al 2010a;Meyer et al 2010;Thorpe et al 2010;Vinardell et al 2010).…”

“…It is evident from the literature that stem cell expansion conditions can significantly influence their subsequent chondrogenic capacity (Tsutsumi et al 2001;Bianchi et al 2003;Solchaga et al 2005;Khan et al 2008;Solchaga et al 2010). This study develops upon previous work to ascertain if such expansion conditions, specifically expansion in the presence of FGF-2, could further enhance the mechanical functionality of cartilaginous constructs engineered using IFP derived MSCs.…”

“…Augmenting MSC expansion conditions to enhance proliferation kinetics while maintaining multipotency is a critical obstacle to overcome in order to engineer mechanically functional tissues for clinical applications. Fibroblast growth factor-2 (FGF-2, also known as basic fibroblast growth factor) has been shown to be a potent stimulator during ex vivo expansion of both chondrocytes (Kato and Gospodarowicz 1985;Martin et al 1999;Martin et al 2001;Veilleux and Spector 2005) and MSCs (Banfi et al 2000;Mastrogiacomo et al 2001;Tsutsumi et al 2001;Bianchi et al 2003;Solchaga et al 2005;Khan et al 2008;Solchaga et al 2010), as well as regulating subsequent differentiation potential. Specifically, bone marrow derived MSCs cultured in the presence of FGF-2 have been shown to be physically smaller and proliferate more rapidly during monolayer expansion (Solchaga et al 2005).…”

“…During chondrogenic differentiation, FGF-2 expanded MSCs have been shown to produce higher levels of proteoglycans with reduced deposition of collagen type I in the peripheral region of pellet cultures while promoting collagen type II formation (Akaogi et al 2004;Solchaga et al 2005). In addition, expansion in the presence of FGF-2 has been shown to enhance chondrogenesis of IFP derived MSCs in pellet culture models (Khan et al 2008).…”

Periodontal regeneration following application of basic fibroblast growth factor-2 in combination with beta tricalcium phosphate in class III furcation defects in dogs

“…Basic fibroblast growth factor-2 (bFGF-2) is a heparinbinding growth factor that exhibits potent angiogenic activity and mitogenic ability in mesenchymal cells [1][2][3][4][5][6][7] and periodontal ligament cells [8][9][10][11] . Several studies have reported that bFGF-2 induces potent periodontal tissue regeneration along with new alveolar bone and cementum formation without aberrant healing such as root resorption and ankylosis in critical size defects of animal models [12][13][14] .…”