• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.9.1-9.10
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• 2018

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.

• Archives of Plastic Surgery
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• v.38 no.5
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• pp.567-575
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• 2011

Purpose: Acellular human dermis is very useful implant for use in plastic and reconstructive surgery. However, the volume of acellular human dermis graft is known to decrease for a long time. Basic fibroblast growth factor (bFGF) is a polypeptide that enhances the collagen synthesis and angiogenesis. In the current study we examined whether bFGF could improve the survival of acellular human dermis ($SureDerm^{(R)}$) by increasing angiogenesis of the graft. Methods: Forty rats were divided into two groups (control and bFGF). A 2-mm thick piece of $SureDerm^{(R)}$ was cut into smaller pieces that were $15{\times}5$ mm in size. Two subcutaneous pockets were made on the back of each rat. Grafts sprayed with bFGF were implanted in the bFGF group and injected with bFGF after transplantation every 3 days for 2 weeks. In the control group, the grafts were treated with phosphate-buffered saline (PBS) instead of bFGF. Four days, and 1, 4, and 12 weeks after the implantation, the grafts were harvested and gross and histologic examinations were performed. Inflammation grade, graft thickness, neocollagen density, and neocapillary count were measured. Results: The bFGF group displayed more rapid accumulation of inflammatory cells with a higher density of neocapillaries, and increased active collagen synthesis. After 12 weeks, the thickness of the grafts in the control and bFGF groups was $75.15{\pm}4.80%$ and $81.79{\pm}5.72%$, respectively, in comparison to the thickness before transplantation. There was a statistically significant difference between both groups ($p$ <0.05). Conclusion: bFGF was effective in reducing the absorption of acellular human dermal grafts by increasing angiogenesis and accelerating engraftment. In conclusion, bFGF may be a good tool for use in acellular human dermal graft transplantation for reconstructive surgery involving soft-tissue defects.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.253-263
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• 2002

Purpose : In order to understand in vivo radiation damage modifying of bFGF on jejunal mucosa, bone marrow and the effect of bFGF on the growth of transplanted mouse sarcoma 180 tumor in mice. Materials and Methods : Mice were treated with $6\;{\mu}g$ of bFGF at 24 hours and 4 hours before exposing to 600 cGy, 800 cGy and 1,000 cGy total body irradiation (TBI), and then exposed to 3,000 cGy local radiation therapy on the tumor bearing thigh. Survival and tumor growth curve were plotted in radiation alone group and combined group of bFGF and irradiation (RT). Histologic examination was performed in another experimental group. Experimental groups consisted of normal control, tumor control, RT (radiation therapy) alone, $6\;{\mu}g$ bFGF alone, combined group of $3\;{\mu}g$ bFGF and irradiation (RT), combined group of $6\;{\mu}g$ bFGF and irradiation (RT). Histologic examination was peformed with H-E staining in marrow, jejunal mucosa, lung and sarcoma 180 bearing tumor. Radiation induced apoptosis was determined in each group with the DNA terminal transferase nick-end labeling method ($ApopTag^{\circledR}$ S7100-kit, Intergen Co.) Results : The results were as follows 1) $6\;{\mu}g$ bFGF given before TBI significantly improved the survival of lethally irradiated mice. bFGF would protect against lethal bone marrow syndrome. 2) $6\;{\mu}g$ bFGF treated group showed a significant higher crypt depth and microvilli length than RT alone group (p<0.05). 3) The bone marrow of bFGF treated group showed less hypocellularity than radiation alone group on day 7 and 14 after TBI (p<0.05), and this protective effect was more evident in $6\;{\mu}g$ bFGF treated group than that of $3\;{\mu}g$ bFGF treated group. 4) bFGF protected against early radiation induced apoptosis in intestinal crypt cell but might have had no antiapoptotic effect in bone marrow stem cell and pulmonary endothelial cells. 5) There was no significant differences in tumor growth rate between tumor control and bFGF alone groups (p>0.05). 6) There were no significant differences in histopathologic findings of lung and mouse sarcoma 180 tumor between radiation alone group and bFGF treated group. Conclusions : Our results suggest that bFGF protects small bowel and bone marrow from acute radiation damage without promoting the inoculated tumor growth in C3H mice. Improved recovery of early responding normal tissue and reduced number of radiation induced apoptosis may be possible mechanism of radioprotective effect of bFGF.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2004.10a
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• pp.110-110
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• 2004

• Korean Journal of Medicinal Crop Science
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• v.15 no.5
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• pp.311-314
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• 2007

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important angiogenic molecules associated with tumor-induced neovascularization. This study was carried out to investigate inhibitory effect of extracts from root of Rehmannia glutinosa LIBOSCHITZ (Rehmannia Radix and Rehmannia Radix Preparata) on endothelial cell proliferation. The methanol extracts from the medicinal herb were fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. Among the four fractions, the n-butanol fraction from R. Radix on exhibited highly effective inhibition (${\approx}79%$ inhibition) on the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and then ethyl acetate fraction from R. Radix (${\approx}45%$ inhibition) at the concentration of $100\;{\mu}g/ml$. The n-butanol fraction efficiently blocked the VEGF- and bFGF-induced HUVEC proliferation in a dose-dependent manner, but did not affect the growth of HT1080 human fibrosarcoma cells. The n-butanol fraction more efficiently blocked the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and VEGF- and bFGF-induced human umbilical vein endothelial cell proliferation than the fraction from R. Radix Preparata. Our results suggest that Rehmannia Radix may be used as a candidate for developing anti-angiogenic agent.

• Journal of Embryo Transfer
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• v.21 no.2
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• pp.157-162
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• 2006

It is well known that unidentified factors in sera, hormones and growth factors promote the proliferation of granulosa cells and nuclear maturation of bovine COCs (cumulus oocytes complexes) in vitro. Attempts had been developed the simple composition of culture media and similar system to in vivo conditions has been applied. In the present study, we investigated the effect of FGF (fibroblast growth factor) on in vitro maturation and in vitro development of Hanwoo COCs. When the COCs were matured in HPM 199 (Inst. of Functional peptide, Japan) containing 0.1, 1 and 10 ng/ml FGF for 24 hr, maturation rates to metaphase II ($70.0{\sim}75.0%$) were significantly higher (p<0.05) than that of control group (0 ng/ml FGF, 37.5%). When matured COCs with FGF were cultured in maturation medium after in vitro fertilization, developmental rates to blastocysts were 9.5, 0 and 2.9%, respectively, compared to 25.0% of the control group (p<0.05). When the matured COCs with FGF were cultured in HPM 199 (IFP971, Inst. of Functional peptide, Japan) containing 10% FBS, 0.8% BSA or 0.1% PVA (polyvinyl alcohol), the blastocyst formation rates were 12.4, 12.8 and 8.5%, respectively, while the rates of matured COCs with FGF and cultured with IVMD and IVD (Inst. of Functional peptide, Japan) without serum were 38.4% and 34.8%, respectively (p<0.05). These results suggested that FGF is available for in vitro maturation of bovine COCs and is not suitable for in vitro development, but further investigation would be need for finding the synergistic autocrine/paracrine fashion of other growth factors in early bovine embryo development.

• Biomaterials and Biomechanics in Bioengineering
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• v.1 no.1
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• pp.27-39
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• 2014

We have previously described a new multilayer alginate microcapsule system, and the goals of the present study were to assess the in vitro function of islets encapsulated in its inner layer, and the angiogenic ability of FGF-1 delivered from the external layer in an omentum pouch. Following isolation and culture, islets were encapsulated in the inner core of microspheres ($500-600{\mu}m$ in diameter) with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers, and both unencapsulated and encapsulated islet function was assessed by a dynamic glucose perifusion. For angiogenesis experiments, one group of microcapsules without FGF-1 (control) and another (test) containing FGF-1 with heparin encapsulated in the external layer were made. One hundred microcapsules of each group were transplanted in Lewis rats (n = 5/group) and were retrieved after 14 days for assessment of angiogenesis. Glucose perifusion of unencapsulated and encapsulated islets resulted in similar stimulation indices. The release of FGF-1 resulted in increased vascular density compared to controls. In conclusion, islets encapsulated in the core of multilayer alginate microcapsules maintain functionality and the microcapsule's external layer is effective in delivery of FGF-1 to enhance graft neovascularization in a retrievable omentum pouch.

• Molecules and Cells
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• v.41 no.2
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• pp.110-118
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• 2018

The objective of this study was to induce the production of isthmic organizer (IsO)-like cells capable of secreting fibroblast growth factor (FGF) 8 and WNT1 from human embryonic stem cells (ESCs). The precise modulation of canonical Wnt signaling was achieved in the presence of the small molecule CHIR99021 ($0.6{\mu}M$) during the neural induction of human ESCs, resulting in the differentiation of these cells into IsO-like cells having a midbrain-hindbrain border (MHB) fate in a manner that recapitulated their developmental course in vivo. Resultant cells showed upregulated expression levels of FGF8 and WNT1. The addition of exogenous FGF8 further increased WNT1 expression by 2.6 fold. Gene ontology following microarray analysis confirmed that IsO-like cells enriched the expression of MHB-related genes by 40 fold compared to control cells. Lysates and conditioned media of IsO-like cells contained functional FGF8 and WNT1 proteins that could induce MHB-related genes in differentiating ESCs. The method for generating functional IsO-like cells described in this study could be used to study human central nervous system development and congenital malformations of the midbrain and hindbrain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1602-1607
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• 2004

3-O-D-galactopyranosylglyceride (GPG; fatty acids R1, R2 = myristic acid 11.62%, palmitic acid 61.90% and oleic acid 26.48%) was isolated from Chrysanthemum coronarium L that has been used for treating renal and cardiovascular diseases as one of vegetables or medicinal drug. However, little was known about the anti-angiogenic activity of GPG. Thus, anti-angiogenic effect of GPG was evaluated in human umbilical vein endothelial cells (HUVECs) in vitro and in vivo. GPG effectively inhibited bFGF-induced migration and invasion of HUVECs in a concentration-dependent manner, whereas it did not inhibit bFGF-induced proliferation and capillary-like tube formation of HUVECs. To examine the mechanism of anti-angiogenic activity of GPG, gelatin zymography was carried out. GPG downregulated the expression of matrix metalloproteinase-2 in a concentration-dependent manner. Furthermore, GPG significantly disrupted bFGF-induced neovascularization on the chick chorioallantoic membrane assay in vivo. These results suggest that 3-O--D-galactopyranosylglyceride may inhibit neovascularization by inhibiting angiogenic activity of endothelial cells via regulation of matrix metalloproteinase-2 (MMP-2).

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.47.1-47.10
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• 2019

Background: Hyaluronic acid (HA) has been applied as a primary biomaterial for temporary soft tissue augmentation and as a carrier for cells and the delivery of growth factors to promote tissue regeneration. Although HA derivatives are the most versatile soft tissue fillers on the market, they are resorbed early, within 3 to 12 months. To overcome their short duration, they can be combined with cells or growth factors. The purpose of this study was to investigate the stimulating effects of human fibroblasts and basic fibroblast growth factors (bFGF) on collagen synthesis during soft tissue augmentation by HA hydrogels and to compare these with the effects of a commercial HA derivative (Restylane^®). Methods: The hydrogel group included four conditions. The first condition consisted of hydrogel (H) alone as a negative control, and the other three conditions were bFGF-containing hydrogel (HB), human fibroblast-containing hydrogel (HF), and human fibroblast/bFGF-containing hydrogel (HBF). In the Restylane^® group (HGF), the hydrogel was replaced with Restylane^® (R, RB, RF, RBF). The gels were implanted subdermally into the back of each nude mouse at four separate sites. Twelve nude mice were used for the hydrogel (n = 6) and Restylane^® groups (n = 6). The specimens were harvested 8 weeks after implantation and assessed histomorphometrically, and collagen synthesis was evaluated by RT-PCR. Results: The hydrogel group showed good biocompatibility with the surrounding tissues and stimulated the formation of a fibrous matrix. HBF and HF showed significantly higher soft tissue synthesis compared to H (p < 0.05), and human collagen type I was well expressed in HB, HF, and HBF; HBF showed the strongest expression. The Restylane^® filler was surrounded by a fibrous capsule without any soft tissue infiltration from the neighboring tissue, and collagen synthesis within the Restylane^® filler could not be observed, even though no inflammatory reactions were observed. Conclusion: This study revealed that HA-based hydrogel alone or hydrogel combined with fibroblasts and/or bFGF can be effectively used for soft tissue augmentation.