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Abstract Objective To determine the efficacy of fibroblast growth factor‐2 (FGF‐2) in treating chronic nonhealing tympanic membrane (TM) perforations. Method Double‐blinded, randomized placebo controlled phase 2 clinical trial for patients with chronic TM perforations of more than 3 months duration with a cross‐over arm. Patients received either FGF‐2 or placebo (sterile water) saturated gelatin sponge in the perforation after rimming the perforation under topical anesthesia. The perforation was then covered with Tisseel fibrin glue. The primary endpoint was complete closure of the TM perforation. Secondary end points included change in hearing and partial TM closure rates. The TM was examined every 3 weeks with otoendoscopy for closure. The treatment was repeated if there was incomplete closure every 3 weeks up to a total of three treatments per arm. Results Seventy four patients were recruited for the study. Fifty seven met eligibility criteria and fifty four completed the study. Ten of 14 perforations closed completely in the placebo group (71.4%) and 23 of 40 perforations closed completely in the FGF‐2 treatment group (57.5%), P value = .36. Pure tone averages and word recognition scores were not statistically significantly different between study groups post‐treatment. After initial complete closure, re‐perforation occurred in seven FGF‐2 treated patients and two placebo patients making the effective final closure rate 40% for FGF and 57% for placebo, respectively. Conclusion No statistically significant difference in tympanic membrane perforation closure rate was found between the FGF‐2 and placebo groups. There were no differences in hearing outcomes between the groups. Level of evidence 1b.

The purpose of this study was to investigate the effect of recombinant human basic fibroblast growth factor (rhbFGF) on nerve regeneration immediately after nerve injury. Partial defects were created in the inferior alveolar nerve of rabbits and were treated with (Experimental group) or without (Control group) rhbFGF for 1–3 weeks. Injured tissues were then characterized immunohistochemically using primary antibodies to S-100; a marker for Schwann cells, and to neurofilament (NF); a marker for axons. The number of S-100-immunopositive cells in the experimental group was significantly increased compared with the control group at weeks 2 and 3 (P < 0.05). The number of NF-immunopositive cells in the experimental group was also significantly increased compared with the control group at week 3 (P < 0.05). These results suggest that application of rhbFGF immediately after partial damage of an inferior alveolar nerve might be effective to promote nerve regeneration. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy of fibroblast growth factor‐2 (FGF‐2) in treating chronic nonhealing tympanic membrane (TM) perforations. Method: Double‐blinded, randomized placebo controlled phase 2 clinical trial for patients with chronic TM perforations of more than 3 months duration with a cross‐over arm. Patients received either FGF‐2 or placebo (sterile water) saturated gelatin sponge in the perforation after rimming the perforation under topical anesthesia. The perforation was then covered with Tisseel fibrin glue. The primary endpoint was complete closure of the TM perforation. Secondary end points included change in hearing and partial TM closure rates. The TM was examined every 3 weeks with otoendoscopy for closure. The treatment was repeated if there was incomplete closure every 3 weeks up to a total of three treatments per arm. Results: Seventy four patients were recruited for the study. Fifty seven met eligibility criteria and fifty four completed the study. Ten of 14 perforations closed completely in the placebo group (71.4%) and 23 of 40 perforations closed completely in the FGF‐2 treatment group (57.5%), P value =.36. Pure tone averages and word recognition scores were not statistically significantly different between study groups post‐treatment. After initial complete closure, re‐perforation occurred in seven FGF‐2 treated patients and two placebo patients making the effective final closure rate 40% for FGF and 57% for placebo, respectively. Conclusion: No statistically significant difference in tympanic membrane perforation closure rate was found between the FGF‐2 and placebo groups. There were no differences in hearing outcomes between the groups. Level of evidence: 1b. [ABSTRACT FROM AUTHOR]

Sclerosing stromal tumours (SSTs) are rare benign tumours and are generally observed in individuals in their teens to 20 s. Many cases are suspected as malignant tumours pre-operatively, owing to their high vascularity on diagnostic imaging. Herein, we aimed to evaluate the expressions of various angiogenic factors in SSTs. The expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) were examined by immunohistochemical staining. Upon immunohistochemistry, overexpressions of VEGF, bFGF, and HGF in the ovarian stroma were observed in SSTs. In the normal ovary, the expressions were strong around the vessels and weak in the stroma of the ovary, while a Sertoli-Leydig cell tumour showed weak staining with VEGF, locally strong staining with bFGF and negative staining with HGF. This is the first report about angiogenic factors such as bFGF, and HGF in SST. Impact statement What is already known on this subject? Sclerosing stromal tumour (SST) is a rare benign tumour with high vascularity. The high vascularity of SSTs are reported to be related to the overexpression of vascular endothelial growth factor (VEGF). But there is no study on the expressions of other angiogenic factors in SST. What do the results this study add? In the immunohistochemical analysis, VEGF, bFGF and HGF were found to be widely stained in SSTs. This results suggest the possibility that the high vascularity seen on diagnostic imaging, and the many small vessels observed microscopically may be related to the expressions of VEGF, bFGF and HGF in SSTs. What are the implications of these findings for clinical practice and/or further research? Our results suggest the possibility that the combined expression pattern of VEGF, bFGF, and HGF may be used as marker of SSTs. [ABSTRACT FROM AUTHOR]

Elastofibroma is a rare tumour that occurs in the subscapular space, and it typically presents in middle-aged and older individuals. The aetiology of elastofibroma remains unknown. Recent, sporadic reports have shown, immunohistologically, that fibroblasts in elastofibroma may produce abnormal elastic and collagen fibres through the action of transforming growth factor-beta (TGF-β), a factor that promotes fibroblast proliferation. However, that finding lacked quantitative measurements and controls. Therefore, in this study, we performed quantitative, immunohistochemical analyses of TGF-β1 and basic fibroblast growth factor (bFGF) in three elastofibromas, and we compared them to ten dermatofibromas and keloids, and five normal skin. In elastofibroma specimens, 16-59 % fibroblasts were positive for TGF-β1 in the cytoplasm, compared to 96 % in dermatofibroma, 93 % in keloid and 2 % in normal dermis specimens. Also, in elastofibroma specimens, 26-67 % of fibroblasts were positive for bFGF in the cytoplasm, compared to 97 % in dermatofibroma, 97 % in keloid, and 22 % in normal dermis specimens. Intriguingly, the tumour size and growth rate were proportional to the percentage of cells positive for bFGF. Finally, greater levels of bFGF expressions in fibroblasts were associated with larger sized elastofibromas. These results suggested that elastofibroma development depended on high expression of TGF-β1 and bFGF. [ABSTRACT FROM AUTHOR]

Neural precursor cell (NPC) dysfunction has been consistently implicated in autism. Induced pluripotent stem cell (iPSC)-derived NPCs from two autism groups (three idiopathic [I-ASD] and two 16p11.2 deletion [16pDel]) were used to investigate if proliferation is commonly disrupted. All five individuals display defects, with all three macrocephalic individuals (two 16pDel, one I-ASD) exhibiting hyperproliferation and the other two I-ASD subjects displaying hypoproliferation. NPCs were challenged with bFGF, and all hyperproliferative NPCs displayed blunted responses, while responses were increased in hypoproliferative cells. mRNA expression studies suggest that different pathways can result in similar proliferation phenotypes. Since 16pDel deletes MAPK3, P-ERK was measured. P-ERK is decreased in hyperproliferative but increased in hypoproliferative NPCs. While these P-ERK changes are not responsible for the phenotypes, P-ERK and bFGF response are inversely correlated with the defects. Finally, we analyzed iPSCs and discovered that 16pDel displays hyperproliferation, while idiopathic iPSCs were normal. These data suggest that NPC proliferation defects are common in ASD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Neural stem progenitor cells (NSPCs) from E13.5 mouse embryos can be maintained in culture under proliferating conditions. Upon growth-factor removal, they may differentiate toward either neuronal or glial phenotypes or both. Exosomes are small extracellular vesicles that are part of the cell secretome; they may contain and deliver both proteins and genetic material and thus play a role in cell–cell communication, guide axonal growth, modulate synaptic activity and regulate peripheral nerve regeneration. In this work, we were interested in determining whether NSPCs and their progeny can produce and secrete extracellular vesicles (EVs) and if their content can affect cell differentiation. Our results indicate that cultured NSPCs produce and secrete EVs both under proliferating conditions and after differentiation. Treatment of proliferating NSPCs with EVs derived from differentiated NSPCs triggers cell differentiation in a dose-dependent manner, as demonstrated by glial- and neuronal-marker expression. [ABSTRACT FROM AUTHOR]

Although myoblast transplantation is an attractive method for muscle regeneration, its efficiency remains limited. The efficacy of myoblast transplantation in combination with the controlled and sustained delivery of basic fibroblast growth factor (bFGF) was investigated. Defects of thigh muscle in Sprague-Dawley (SD) rats were created, and GFP-positive myoblasts were subsequently transplanted. The rats were divided into three groups. In control group 1 (C1) only myoblasts were transplanted, while in control group 2 (C2) myoblasts were introduced along with empty gelatin hydrogel microspheres. In the experimental group (Ex), myoblasts were transplanted along with bFGF incorporated into gelatin hydrogel microspheres. Four weeks after transplantation, GFP-positive myoblasts were found to be integrated into the recipient muscle and to contribute to muscle fibre regeneration in all groups. A significantly higher expression level of GFP in the Ex group demonstrated that the survival rate of transplanted myoblasts in Ex was remarkably improved compared with that in C1 and C2. Furthermore, myofibre regeneration, characterized by centralization of the nuclei, was markedly accelerated in Ex. The expression level of CD31 in Ex was higher than that in both C1 and C2, but the differences were not statistically significant. A significantly higher expression level of Myogenin and a lower expression level of MyoD1 were both observed in Ex after 4 weeks, suggesting the promotion of differentiation to myotubes. Our findings suggest that the controlled and sustained release of bFGF from gelatin hydrogel microspheres improves the survival rate of transplanted myoblasts and promotes muscle regeneration by facilitating myogenesis rather than angiogenesis., (Copyright © 2013 John Wiley & Sons, Ltd.)