Fibroblast Growth Factor-2 Stimulates Adipogenic Differentiation of Human Adipose-derived Stem Cells

Kakudo, Natsuko; Shimotsuma, Ayuko; Kusumoto, Kenji

doi:10.5361/jkmu.61.200

Cited by 4 publications

(7 citation statements)

References 15 publications

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“…Fibroblast growth factor-2 has been shown to suppress differentiation of MSCs by inducing Twist-2 and Sprouty4. 43,44 In vivo evidence for the negative adipogenic function of FGF-2 also exists with the observation that MSCs from mice deficient in FGF-2 displayed enhanced adipogenic potential. 44 The finding of increased FGF-2 in the cell lysate of ADSCs from breast cancer patients correlates with the reduced adipogenic capacity observed in these ADSCs in our study.…”

Section: Discussionmentioning

confidence: 99%

Oncological Risk in Autologous Stem Cell Donation for Novel Tissue-Engineering Approaches to Postmastectomy Breast Regeneration

O’Halloran

Khan

Gilligan

et al. 2019

Breast Cancer�(Auckl)

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Adipose tissue engineering using adipose-derived stem cells (ADSCs) has emerged as an opportunity to develop novel approaches to postmastectomy breast reconstruction with the potential for an autologous tissue source with a natural appearance and texture. As of yet, the role of ADSCs in breast cancer development and metastasis is not completely understood; therefore, we must consider the oncological safety of employing an autologous source of ADSCs for use in breast regeneration. This study investigated the regenerative properties of ADSCs isolated from breast cancer patients, including those who had received neoadjuvant chemotherapy, and noncancer controls. The ADSCs were characterised for several parameters central to tissue regeneration, including cell viability, proliferation, differentiation potential, and cytokine secretion. A stem cell population was isolated and confirmed by flow cytometry and multilineage differentiation. There was no difference in cell phenotype or surface antigen expression between ADSCs from different sources. Adipose-derived stem cells isolated from the breast of cancer patients exhibited reduced adipogenic differentiation potential compared with ADSCs from other sources. The greatest degree of adipogenic differentiation was observed in ADSCs isolated from the subcutaneous abdominal fat of noncancer controls. The proliferation rate of ADSCs isolated from the breast of cancer patients was increased compared with other sources; however, it was decreased in ADSCs isolated from breast cancer patients who had recently been treated with neoadjuvant chemotherapy. A number of cytokines were detected in the cell conditioned media of ADSCs from different sources, including matrix metalloproteinase-2 (MMP-2), which was detected at higher levels in the secretome of ADSCs from breast cancer patients compared with noncancer controls. This study provides important information relating to the suitability of ADSCs as an autologous cell source for adipose tissue engineering in postcancer reconstruction. Results indicate that while the surface phenotype does not differ, the differentiation capacity, proliferative rate, and secreted cytokine profile are affected by the presence or treatment of breast cancer. These findings support further investigation into the regenerative potential of these ADSCs, if they are to be considered in clinical reconstructive strategies.

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Section: Discussionmentioning

confidence: 99%

Oncological Risk in Autologous Stem Cell Donation for Novel Tissue-Engineering Approaches to Postmastectomy Breast Regeneration

O’Halloran

Khan

Gilligan

et al. 2019

Breast Cancer�(Auckl)

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“…61 The effects of several different growth factors in MSC lineage specification was extensively studied in vitro in chondrogenesis, [62][63][64] osteogenesis, [64][65][66][67][68] and adipogenesis. [69][70][71] Many growth factors promoting MSCs proliferation and differentiation have been described, but the exact molecular mechanisms by which they act is still unclear. To better understand these mechanisms, it is first necessary to identify the factors that promote proliferation, differentiation, or retain the differentiation state of MSCs.…”

Section: The Ecm or Tissue Microenvironment Directs Mscs Lineage Specificationmentioning

confidence: 99%

Reproductive Stem Cell Differentiation: Extracellular Matrix, Tissue Microenvironment, and Growth Factors Direct the Mesenchymal Stem Cell Lineage Commitment

et al. 2013

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The mesenchymal stem cells (MSCs) have awakened interest in regenerative medicine due to its high capability to proliferate and differentiate in multiple specialized lineages under defined conditions. The reproductive system is considered a valuable source of MSCs, which needs further investigations. Many factors have been reported as critical for these cell lineage specification and determination. In this review, we discuss the main effects of extracellular matrix or tissue environment and growth factors in the cell lineage commitment, including the reproductive stem cells. The MSCs responses to culture medium stimuli or to soluble factors probably occur through several intracellular activation pathways. However, the molecular mechanisms in which the cells respond to these mechanical or chemical perturbations remain elusive. Recent findings suggest a synergic effect of microenvironment and soluble cell culture factors affecting cell differentiation. For future applications in cell therapy, protocols of reproductive MSCs differentiation must be established.

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“…While osteoblasts and adipocytes arise from mesenchymal stem cells (MSC), a common progenitor cell type located in bone marrow, adipose tissue and other adult organs ( 7 ) , the lineage commitment of multipotent MSC depends on several factors including growth factor signalling. Adipogenesis is regulated by several growth factors starting from determination, commitment to preadipocytes and lipid accumulation stages ( 8 ) involving several receptor kinase signalling pathways such as epithelial growth factor (EGF), fibroblast growth factor (FGF), vascular endothelical growth factor (VEGF) and insulin-like growth factor (IGF) ( 9 , 10 ) . Sprouty (Spry) and Spred (Spry-related protein) family proteins are evolutionarily conserved inhibitors of receptor tyrosine kinase signalling ( 11 – 13 ) .…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction

Urs

Henderson

et al. 2011

Br J Nutr

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We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss.

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Fibroblast Growth Factor-2 Stimulates Adipogenic Differentiation of Human Adipose-derived Stem Cells

Cited by 4 publications

References 15 publications

Oncological Risk in Autologous Stem Cell Donation for Novel Tissue-Engineering Approaches to Postmastectomy Breast Regeneration

Oncological Risk in Autologous Stem Cell Donation for Novel Tissue-Engineering Approaches to Postmastectomy Breast Regeneration

Reproductive Stem Cell Differentiation: Extracellular Matrix, Tissue Microenvironment, and Growth Factors Direct the Mesenchymal Stem Cell Lineage Commitment

Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction

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