Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells

Chiou, Michael; Xu, Yue; Longaker, Michael T.

doi:10.1016/j.bbrc.2006.02.171

Cited by 115 publications

(90 citation statements)

References 26 publications

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“…33,34 The cellular infiltration around capillary sprouts is where immature adipocytes occur at 6 weeks and has been observed by others. 32 PDGF-BB and FGF-2 stimulate mesenchymal cell proliferation and migration, 15,29,[35][36][37] PDGF-BB stimulates preadipocyte differentiation, 30 whereas FGF-2 stimulates proliferation of adipose precursor cells. 38 Given the evidence that both factors, via several mechanisms, positively influence adipose tissue growth, it is not surprising that our study showed an increase in adipose tissue for individual applications of FGF-2 and PDGF-BB.…”

Section: Discussionmentioning

confidence: 99%

“…13 Fibroblastic growth factor (FGF)-2 is important in wound healing and angiogenesis, acting as an angiogenic cytokine promoting endothelial proliferation and capillary formation, 14 and also stimulates proliferation and migration of mesenchymal cells. 15 Platelet-derived growth factor (PDGF)-BB is involved in pericyte recruitment around capillaries during angiogenesis. 16 Angiogenic growth factors have been used in tissue repair studies including those related to improving ischemic conditions.…”

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confidence: 99%

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Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

Rophael

Craft

Palmer

et al. 2007

The American Journal of Pathology

118

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De novo tissue generation stimulated by three angiogenic growth factors administered in a factorial design was studied in an in vivo murine tissue engineering chamber. A silicone chamber was implanted around the epigastric pedicle and filled with Matrigel with 100 ng/ml of recombinant mouse vascular endothelial growth factor-120 (VEGF 120 ), recombinant human basic fibroblastic growth factor (FGF-2), or recombinant rat platelet-derived growth factor-BB (PDGF-BB) added as single, double, or triple combinations. Angiogenesis, supporting tissue ingrowth, and adipogenesis were assessed at 2 and 6 weeks by immunohistochemistry and morphometry. At 2 weeks angiogenesis was synergistically enhanced by VEGF 120 ؉ FGF-2 (P ‫؍‬ 0.019). FGF-2 (P ‫؍‬ 0.008) and PDGF-BB (P ‫؍‬ 0.01) significantly increased connective tissue/inflammatory cell infiltrate (macrophages, pericytes, and preadipocytes) in double and triple combinations compared with control. At 6 weeks sequential addition of growth factors increased the percent volume of adipose tissue (P < 0.0005, each main effect), with a synergistic increase in adipose tissue in combination treatments (P < 0.0005). Groups containing 300 ng/ml of single growth factors produced significantly less adipose tissue than the triple growth factor combination (P < 0.0005, VEGF 120 and PDGF-BB; P < 0.001, FGF-2). In conclusion, angiogenic growth factor combinations increased early angiogenesis and cell infiltration resulting in synergistically increased adipose tissue growth at 6 weeks. Two way and higher level synergies are likely to be important in therapeutic applications of angiogenic growth factors.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

Rophael

Craft

Palmer

et al. 2007

The American Journal of Pathology

118

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“…The osteogenic and proliferative potential of ASCs can also be preserved by expanding the cells in the presence of bFGF (Quarto and Longaker 2006). For chondrogenic activity, several studies have confirmed the ability of bFGF, while in monolayer culture and also during induction, to significantly enhance the chondrogenic potential of MSCs and ASCs (Chiou et al 2006;Coleman et al 2007;Mastrogiacomo et al 2001;Tsutsumi et al 2001). It has also been shown that ASCs grown in the presence of both bFGF and EGF along with TGF-β maintain telomerase activity throughout 9 passages while maintaining the potential for chondrogenic differentiation (Estes et al 2006b).…”

Section: Introductionmentioning

confidence: 97%

Monolayer cell expansion conditions affect the chondrogenic potential of adipose‐derived stem cells

Estes

Diekman

Guilak

2008

Biotech & Bioengineering

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Adipose-derived stem cells (ASCs) are an abundant, readily available population of multipotent progenitor cells that reside in adipose tissue. Isolated ASCs are typically expanded in monolayer on standard tissue culture plastic with a basal medium containing 10% fetal bovine serum. However, recent data suggests that altering the monolayer expansion conditions by using suspension culture plastic, adding growth factors to the medium, or adjusting the seeding density may affect the self-renewal rate, multipotency, and lineage-specific differentiation potential of the ASCs. We hypothesized that variation in any of these expansion conditions would influence the chondrogenic potential of ASCs. ASCs were isolated from human liposuction waste tissue and expanded through two passages with different tissue culture plastic, feed medium, and cell seeding densities. Once expanded, the cells were cast in an agarose gel and subjected to identical chondrogenic culture conditions for 7 days, at which point cell viability, radiolabel incorporation, and gene expression were measured. High rates of matrix synthesis upon chondrogenic induction were mostly associated with smaller cells, as indicated by cell width and area on tissue culture plastic, and it appears that expansion in a growth factor supplemented medium is important in maintaining this morphology. All end-point measures were highly dependent on the specific monolayer culture conditions. These results support the hypothesis that monolayer culture conditions may "prime" the cells or predispose them towards a specific phenotype and thus underscore the importance of early culture conditions in determining the growth and differentiation potential of ASCs.

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“…FGF-2 significantly increases the proliferation of ATSCs and enhances chondrogenesis in a three-dimensional micromass culture. 12 However, FGF-2 also reportedly inhibits osteogenesis in mouse ATSCs and sustains their proliferative and osteogenic potential. 13 Recently, FGF-2 has been shown to maintain the self-renewing state human ATSCs.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Ex Vivo Expansion of Human Adipose Tissue–Derived Mesenchymal Stromal Cells by Fibroblast Growth Factor-2 and Dexamethasone

Lee

Lim

Khang

et al. 2009

Tissue Engineering Part A

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In the present study, we investigated the ex vivo expansion of human adipose tissue-derived mesenchymal stromal cells (ATSCs) to identify factors that promoted efficient expansion while preserving stem cell potential. We examined several growth factors and steroids, and found that the combination of a low concentration of fibroblast growth factor-2 (FGF-2) (1 ng=mL) and dexamethasone (DEX) or betamethasone (BET) enhanced the proliferation of ATSCs by approximately 30-60% as compared to control. Enhanced proliferation under these conditions was confirmed using ATSCs isolated from three independent donors. ATSCs that were expanded in the presence of FGF-2 and DEX for 5 days were capable of differentiating into either osteoblastic or adipogenic cells, and the cells were positive for the mesenchymal stem cell markers such as CD29, CD44, CD90, CD105, and CD146, suggesting that the stem cell potential of the ATSCs was preserved. Analysis of signaling pathway revealed that tyrosine phosphorylation of Src kinase was dramatically increased in response to FGF-2 and DEX, suggesting the involvement of Src-dependent pathways in the stimulatory mechanism of proliferation of ATSCs by FGF-2 and DEX. Moreover, Src family kinase inhibitors (SU6656 and Src kinase inhibitor I) substantially reduced the FGF-2 and DEX-induced proliferation of ATSCs. SU6656 also inhibited the osteogenic and adipogenic differentiation of ATSCs. The results of the current study demonstrate that FGF-2 in combination with DEX stimulates the proliferation and osteoblastic and adipogenic differentiation of ATSCs through a Src-dependent mechanism, and that FGF-2 and DEX promote the efficient ex vivo expansion of ATSCs.

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Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells

Cited by 115 publications

References 26 publications

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis

Monolayer cell expansion conditions affect the chondrogenic potential of adipose‐derived stem cells

Enhanced Ex Vivo Expansion of Human Adipose Tissue–Derived Mesenchymal Stromal Cells by Fibroblast Growth Factor-2 and Dexamethasone

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