21 results
Search Results
Now showing 1 - 10 of 21
Article Citation - WoS: 5Citation - Scopus: 6Clinic-Oriented Injectable Smart Material for the Treatment of Diabetic Wounds: Coordinating the Release of Gm-Csf and Vegf(Elsevier, 2024) Kinali, Hurmet; Kalaycioglu, Gokce Dicle; Boyacioglu, Ozge; Korkusuz, Petek; Aydogan, Nihal; Vargel, IbrahimChronic wounds are often caused by diabetes and present a challenging clinical problem due to vascular problems leading to ischemia. This inhibits proper wound healing by delaying inflammatory responses and angiogenesis. To address this problem, we have developed injectable particle-loaded hydrogels which sequentially release Granulocyte-macrophage- colony-stimulating-factor (GM-CSF) and Vascular endothelial growth factor (VEGF) encapsulated in polycaprolactone-lecithin-geleol mono-diglyceride hybrid particles. GM-CSF promotes inflammation, while VEGF facilitates angiogenesis. The hybrid particles (200 -1000 nm) designed within the scope of the study can encapsulate the model proteins Bovine Serum Albumin 65 +/- 5 % and Lysozyme 77 +/- 10 % and can release stably for 21 days. In vivo tests and histological findings revealed that in the hydrogels containing GM-CSF/VEGF-loaded hybrid particles, wound depth decreased, inflammation phase increased, and fibrotic scar tissue decreased, while mature granulation tissue was formed on day 10. These findings confirm that the hybrid particles first initiate the inflammation phase by delivering GM-CSF, followed by VEGF, increasing the number of vascularization and thus increasing the healing rate of wounds. We emphasize the importance of multi-component and sequential release in wound healing and propose a unifying therapeutic strategy to sequentially deliver ligands targeting wound healing stages, which is very important in the treatment of the diabetic wounds.Article Citation - WoS: 24Citation - Scopus: 27Mesenchymal Stem Cells Promote Spermatogonial Stem/Progenitor Cell Pool and Spermatogenesis in Neonatal Mice in Vitro(Nature Portfolio, 2022) Onen, Selin; Kose, Sevil; Yersal, Nilgun; Korkusuz, PetekPrepubertal cancer treatment leads to irreversible infertility in half of the male patients. Current in vitro spermatogenesis protocols and cryopreservation techniques are inadequate to expand spermatogonial stem/progenitor cells (SSPC) from testicles. Bone marrow derived mesenchymal stem cells (BM-MSC) bearing a close resemblance to Sertoli cells, improved spermatogenesis in animal models. We asked if a co-culture setup supported by syngeneic BM-MSC that contributes to the air-liquid interphase (ALI) could lead to survival, expansion and differentiation of SSPCs in vitro. We generated an ALI platform able to provide a real-time cellular paracrine contribution consisting of syngeneic BM-MSCs to neonatal C57BL/6 mice testes. We aimed to evaluate the efficacy of this culture system on SSPC pool expansion and spermatogenesis throughout a complete spermatogenic cycle by measuring the number of total germ cells (GC), the undifferentiated and differentiating spermatogonia, the spermatocytes and the spermatids. Furthermore, we evaluated the testicular cell cycle phases, the tubular and luminal areas using histochemical, immunohistochemical and flow cytometric techniques. Cultures in present of BM-MSCs displayed survival of ID4(+) spermatogonial stem cells (SSC), expansion of SALL4(+) and OCT4(+) SSPCs, VASA(+) total GCs and Ki67(+) proliferative cells at 42 days and an increased number of SCP3(+) spermatocytes and Acrosin(+) spermatids at 28 days. BM-MSCs increased the percentage of mitotic cells within the G2-M phase of the total testicular cell cycle increased for 7 days, preserved the cell viability for 42 days and induced testicular maturation by enlargement of the tubular and luminal area for 42 days in comparison to the control. The percentage of PLZF(+) SSPCs increased within the first 28 days of culture, after which the pool started to get smaller while the number of spermatocytes and spermatids increased simultaneously. Our findings established the efficacy of syngeneic BM-MSCs on the survival and expansion of the SSPC pool and differentiation of spermatogonia to round spermatids during in vitro culture of prepubertal mice testes for 42 days. This method may be helpful in providing alternative cures for male fertility by supporting in vitro differentiated spermatids that can be used for round spermatid injection (ROSI) to female oocyte in animal models. These findings can be further exploited for personalized cellular therapy strategies to cure male infertility of prepubertal cancer survivors in clinics.Article Citation - WoS: 1Citation - Scopus: 2Cannabinoid Receptor Ligands Modulate Fibrosis and Inflammation in Idiopathic Pulmonary Fibrosis: a Preliminary Study(Tubitak Scientific & Technological Research Council Turkey, 2024) Kose, Sevil; Onen, Selin; Gizer, Merve; Boduroglu, Esin; Gonullu, Ugur; Korkusuz, PetekBackground/aim: No specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF) exists. Therefore, new antiinflammatory therapeutic strategies are needed. Cannabinoids (CBs), known for their inflammation-modulating and antifibrotic effects, may be potential medication candidates for treating IPF. We aim to evaluate the inflammation-modulating and antifibrotic effects of CB receptor (CBR) agonists and antagonists in lipopolysaccharide-stimulated normal human lung fibroblast, epithelial cells, IPF fibroblast cells, and monocytes. Materials and methods: We detected CBRs in normal human lung fibroblasts (LL24) and IPF fibroblast cells (LL29), epithelial cells (A549) and monocytes (THP-1) by flow cytometry. We determined TGF-(31, IL-8, and TNF-alpha inflammatory cytokines in the LL24, LL29, A549, and THP-1 cell culture supernatants on days 1 and 5 by ELISA. We evaluated the cell viability in LL24, LL29, and A549 cells on days 1, 3, and 5 spectrophotometrically and detected collagen Type I (ColI) production in the LL24 and LL29 cell culture supernatants on days 1, 3, and 5 by ELISA. Results: LL24, LL29, A549, and THP-1 cells exhibited CB1 (CB1R) and CB2 (CB2R) receptors. CB1R and CB2R agonists WIN55,2122 and JWH015 inhibited fibroblastic and epithelial cell proliferation on day 5. TGF-(31 and TNF-alpha release increased, while IL-8 release decreased in LL24, LL29, A549, and THP-1 cells in response to the administration of WIN55,212-2 and JWH015 at a 10-2 mM concentration. CB1R and CB2R antagonists AM251 and AM630 did not block agonistic responses, suggesting a nonclassical CBRmediated pathway. CB2R agonist JWH015 decreased ColI expression in IPF lung fibroblasts LL29 on day 3. Conclusion: These results suggest that CB signaling regulates the progression of pulmonary inflammation and fibrosis via CBR activation. This may offer a potential pharmacological tool for developing antifibrosis therapies.Book Part Citation - WoS: 18Citation - Scopus: 23Stem Cell and Advanced Nano Bioceramic Interactions(Springer-verlag Singapore Pte Ltd, 2018) Kose, Sevil; Kankilic, Berna; Gizer, Merve; Dede, Eda Ciftci; Bayramli, Erdal; Korkusuz, Petek; Korkusuz, Feza; Ciftci Dede, EdaBioceramics are type of biomaterials generally used for orthopaedic applications due to their similar structure with bone. Especially regarding to their osteoinductivity and osteoconductivity, they are used as biodegradable scaffolds for bone regeneration along with mesenchymal stem cells. Since chemical properties of bioceramics are important for regeneration of tissue, physical properties are also important for cell proliferation. In this respect, several different manufacturing methods are used for manufacturing nano scale bioceramics. These nano scale bioceramics are used for regeneration of bone and cartilage both alone or with other types of biomaterials. They can also act as carrier for the delivery of drugs in musculoskeletal infections without causing any systemic toxicity.Article Citation - WoS: 37Citation - Scopus: 44The Effect of Boron-Containing Nano-Hydroxyapatite on Bone Cells(Humana Press inc, 2020) Gizer, Merve; Kose, Sevil; Karaosmanoglu, Beren; Taskiran, Ekim Z.; Berkkan, Aysel; Timucin, Muharrem; Korkusuz, PetekMetabolic diseases or injuries damage bone structure and self-renewal capacity. Trace elements and hydroxyapatite crystals are important in the development of biomaterials to support the renewal of bone extracellular matrix. In this study, it was assumed that the boron-loaded nanometer-sized hydroxyapatite composite supports the construction of extracellular matrix by controlled boron release in order to prevent its toxic effect. In this context, boron release from nanometer-sized hydroxyapatite was calculated by ICP-MS as in large proportion within 1 h and continuing release was provided at a constant low dose. The effect of the boron-containing nanometer-sized hydroxyapatite composite on the proliferation of SaOS-2 osteoblasts and human bone marrow-derived mesenchymal stem cells was evaluated by WST-1 and compared with the effects of nano-hydroxyapatite and boric acid. Boron increased proliferation of mesenchymal stem cells at high doses and exhibited different effects on osteoblastic cell proliferation. Boron-containing nano-hydroxyapatite composites increased osteogenic differentiation of mesenchymal stem cells by increasing alkaline phosphatase activity, when compared to nano-hydroxyapatite composite and boric acid. The molecular mechanism of effective dose of boron-containing hydroxyapatite has been assessed by transcriptomic analysis and shown to affect genes involved in Wnt, TGF-beta, and response to stress signaling pathways when compared to nano-hydroxyapatite composite and boric acid. Finally, a safe osteoconductive dose range of boron-containing nano-hydroxyapatite composites for local repair of bone injuries and the molecular effect profile in the effective dose should be determined by further studies to validation of the regenerative therapeutic effect window.Article Citation - WoS: 1Citation - Scopus: 1Topical Intranasal Insulin Enhances Healing of Nasal Mucosa: an Experimental Animal Study(Sage Publications inc, 2023) Kulekci, Cagri; Ozer, Serdar; Onen, Selin; Korkusuz, Petek; Yilmaz, TanerObjective Aim of this study was to evaluate the effect of topical intranasal insulin on healing of nasal mucosa in a rat model. Methods Forty-eight Wistar rats, weighing between 250 and 300 g and aged 10-12 weeks were used and randomized into two equal groups. 1.9 mm curette was introduced through the left nostril and 1.9 mm mucosa from the left nasal septum was curetted. Postoperatively, animals in the control group received 1 mL of physiologic saline, 3 times a day in a nasal irrigation fashion. Animals in the experimental group received 1 mL of 5 IU/mL regular insulin in saline solution. Subjects were sacrificed after 5, 10, and 15 days and macroscopic and histomorphometric evaluations were performed. Results There were no mucosal synechiae and septal perforation macroscopically. Histological examination revealed that the defect size reduction was 21% in the saline group versus 56% in the insulin group on the fifth day (p = 0.006). There was 62% defect reduction in the saline group versus 79% in the insulin group on the 10th day (p = 0.034). On the 15th day, only 67% of saline group animals had complete defect closure, whereas 100% of animals treated with insulin had complete closure (92% vs 100% mucosal defect reduction, p = 0.036). Both edema and inflammation were less in the insulin group on 15th day (p = 0.006; p = 0.023, respectively). Conclusion The results from this study support the safety and efficacy of topical insulin on wound healing in the literature. This study could guide further experimental studies that examine human sinonasal wound healing.Book Part Citation - WoS: 13Citation - Scopus: 14Neurological Regulation of the Bone Marrow Niche(Springer international Publishing Ag, 2020) Aerts-Kaya, Fatima; Ulum, Baris; Mammadova, Aynura; Kose, Sevil; Aydin, Gozde; Korkusuz, Petek; Uckan-Cetinkaya, DuyguThe bone marrow (BM) hematopoietic niche is the microenvironment where in the adult hematopoietic stem and progenitor cells (HSPCs) are maintained and regulated. This regulation is tightly controlled through direct cell-cell interactions with mesenchymal stromal stem (MSCs) and reticular cells, adipocytes, osteoblasts and endothelial cells, through binding to extracellular matrix molecules and through signaling by cytokines and hematopoietic growth factors. These interactions provide a healthy environment and secure the maintenance of the HSPC pool, their proliferation, differentiation and migration. Recent studies have shown that innervation of the BM and interactions with the peripheral sympathetic neural system are important for maintenance of the hematopoietic niche, through direct interactions with HSCPs or via interactions with other cells of the HSPC microenvironment. Signaling through adrenergic receptors (ARs), opioid receptors (ORs), endocannabinoid receptors (CRs) on HSPCs and MSCs has been shown to play an important role in HSPC homeostasis and mobilization. In addition, a wide range of neuropeptides and neurotransmitters, such as Neuropeptide Y (NPY), Substance P (SP) and Tachykinins, as well as neurotrophins and neuropoietic growth factors have been shown to be involved in regulation of the hematopoietic niche. Here, a comprehensive overview is given of their role and interactions with important cells in the hematopoietic niche, including HSPCs and MSCs, and their effect on HSPC maintenance, regulation and mobilization.Article Citation - WoS: 3Citation - Scopus: 4A Novel Injectable Nanotherapeutic Platform Increasing the Bioavailability and Anti-Tumor Efficacy of Arachidonylcyclopropylamide on an Ectopic Non-Small Cell Lung Cancer Xenograft Model: A Randomized Controlled Trial(Elsevier, 2025) Boyacioglu, Ozge; Varan, Cem; Bilensoy, Erem; Aykut, Zaliha Gamze; Recber, Tuba; Nemutlu, Emirhan; Korkusuz, PetekRapid progressing non-small cell lung adenocarcinoma (NSCLC) decreases treatment success. Cannabinoids emerge as drug candidates for NSCLC due to their anti-tumoral capabilities. We previously reported the controlled release of Arachidonylcyclopropylamide (ACPA) selectively targeting cannabinoid 1 (CB1) receptor in NSCLC cells in vitro. Hydrophobic polymers like polycaprolactone (PCL) offer prolonged circulation time and slower drug clearance which is suitable for hydrophobic molecules like ACPA. Thus, the extended circulation time with enhanced bioavailability and half-life of nanoparticular ACPA is crucial for its therapeutic performance in the tumor area. We assumed that a novel high technology-controlled release system increasing the bioavailability of ACPA compared to free ACPA could be transferred to the clinic when validated in vivo. Plasma profile of ACPA and ACPA-loaded PCL-based nanomedicine by LC-MS/MS and complete blood count (CBC) was assessed in wild-type Balb/c mice. Tumor growth in nanomedicine-applied NSCLC-induced athymic nude mice was assessed using bioluminescence imaging (BLI) and caliper measurements, histomorphometry,immunohistochemistry, TUNEL assay, and Western blot on days 7-21. Injectable NanoACPA increased its systemic exposure to tissues 5.5 times and maximum plasma concentration 6 times higher than free ACPA by substantially improving bioavailability. The potent effect of NanoACPA lasted for at least two days on ectopic NSCLC model through Akt/PI3K, Ras/MEK/Erk, and JNK pathways that diminished Ki-67 proliferative and promoted TUNEL apoptotic cell scores on days 7-21. The output reveals that NanoACPA platform could be a chemotherapeutic for NSCLC in the clinic following scale-up GLP/GMP-based phase trials, owing to therapeutic efficacy at a safe low dose window.Article Citation - WoS: 28Citation - Scopus: 30Acpa Decreases Non-Small Cell Lung Cancer Line Growth Through Akt/Pi3k and Jnk Pathways in Vitro(Springernature, 2021) Boyacioglu, OEzge; Bilgic, Elif; Varan, Cem; Bilensoy, Erem; Nemutlu, Emirhan; Sevim, Duygu; Korkusuz, PetekTherapeutic agents used for non-small cell lung cancer (NSCLC) have limited curative efficacy and may trigger serious adverse effects. Cannabinoid ligands exert antiproliferative effect and induce apoptosis on numerous epithelial cancers. We confirmed that CB1 receptor (CB1R) is expressed in NSCLC cells in this study. Arachidonoylcyclopropylamide (ACPA) as a synthetic, CB1R-specific ligand decreased proliferation rate in NSCLC cells by WST-1 analysis and real-time proliferation assay (RTCA). The half-maximal inhibitory concentration (IC50) dose of ACPA was calculated as 1.39x10(-12)M. CB1 antagonist AM281 inhibited the antiproliferative effect of ACPA. Flow cytometry and ultrastructural analyzes revealed significant early and late apoptosis with diminished cell viability. Nano-immunoassay and metabolomics data on activation status of CB1R-mediated pro-apoptotic pathways found that ACPA inhibited Akt/PI3K pathway, glycolysis, TCA cycle, amino acid biosynthesis, and urea cycle and activated JNK pathway. ACPA lost its chemical stability after 24hours tested by liquid chromatography-mass spectrometry (LC-MS/MS) assay. A novel ACPA-PCL nanoparticle system was developed by nanoprecipitation method and characterized. Sustained release of ACPA-PCL nanoparticles also reduced proliferation of NSCLC cells. Our results demonstrated that low dose ACPA and ACPA-PCL nanoparticle system harbor opportunities to be developed as a novel therapy in NSCLC patients that require further in vivo studies beforehand to validate its anticancer effect.Book Part A Niche-Based Perspective to Stem and Cancer Stem Cells of the Lung(Springer, 2025) Boyacıoğlu, Özge; Kalali, Berfin Deniz; Tongün, Ege; Korkusuz, PetekLungs carry the principle function for the conduction and exchange of air through the primary, secondary, tertiary bronchi, bronchioles, and alveoli, resulting in the exchange of oxygen to carbon dioxide within the human tissues. Lung stem and progenitor cells enable differentiation of parenchymal and stromal elements and provide homeostasis and regeneration in the microenvironment against pulmonary diseases. Tumor-initiating cancer cells (TICs) refer to a subpopulation named as cancer stem cells (CSCs) of lung cancer exhibiting high self-renewal and proliferation capacity by Notch, Hippo, Hedgehog, and Wnt signaling pathways that leads to tumor development or recurrence. Lung cancer stem cells (LCSCs) are characterized by distinct genotypic or phenotypic alterations compared to healthy lung stem cells (LSCs) that provide a potential target to treat lung cancer. Therefore, understanding the cascades responsible for the transformation of healthy to CSCs is essential to develop new targeted therapy approaches. In this chapter, we precisely highlight the latest researches on LSCs and CSCs, key signaling mechanisms within the perspective of novel targeted therapy strategies. © 2025 Elsevier B.V., All rights reserved.
- «
- 1 (current)
- 2
- 3
- »