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Article Citation - WoS: 16Citation - Scopus: 19A Pumpless Monolayer Microfluidic Device Based on Mesenchymal Stem Cell-Conditioned Medium Promotes Neonatal Mouse in Vitro Spermatogenesis(Bmc, 2023) Onen, Selin; Atik, Ali Can; Gizer, Merve; Kose, Sevil; Yaman, Onder; Kulah, Haluk; Korkusuz, PetekBackgroundChildhood cancer treatment-induced gonadotoxicity causes permanent infertility/sub-infertility in nearly half of males. The current clinical and experimental approaches are limited to cryopreservation of prepubertal testicular strips and in vitro spermatogenesis which are inadequate to achieve the expanded spermatogonial stem/progenitor cells and spermatogenesis in vitro. Recently, we reported the supportive effect of bone marrow-derived mesenchymal cell co-culture which is inadequate after 14 days of culture in static conditions in prepubertal mouse testis due to lack of microvascular flow and diffusion. Therefore, we generated a novel, pumpless, single polydimethylsiloxane-layered testis-on-chip platform providing a continuous and stabilized microfluidic flow and real-time cellular paracrine contribution of allogeneic bone marrow-derived mesenchymal stem cells.MethodsWe aimed to evaluate the efficacy of this new setup in terms of self-renewal of stem/progenitor cells, spermatogenesis and structural and functional maturation of seminiferous tubules in vitro by measuring the number of undifferentiated and differentiating spermatogonia, spermatocytes, spermatids and tubular growth by histochemical, immunohistochemical, flow cytometric and chromatographic techniques.ResultsBone marrow-derived mesenchymal stem cell-based testis-on-chip platform supported the maintenance of SALL4(+) and PLZF(+) spermatogonial stem/progenitor cells, for 42 days. The new setup improved in vitro spermatogenesis in terms of c-Kit(+) differentiating spermatogonia, VASA(+) total germ cells, the meiotic cells including spermatocytes and spermatids and testicular maturation by increasing testosterone concentration and improved tubular growth for 42 days in comparison with hanging drop and non-mesenchymal stem cell control.ConclusionsFuture fertility preservation for male pediatric cancer survivors depends on the protection/expansion of spermatogonial stem/progenitor cell pool and induction of in vitro spermatogenesis. Our findings demonstrate that a novel bone marrow-derived mesenchymal stem cell-based microfluidic testis-on-chip device supporting the maintenance of stem cells and spermatogenesis in prepubertal mice in vitro. This new, cell therapy-based microfluidic platform may contribute to a safe, precision-based cell and tissue banking protocols for prepubertal fertility restoration in future.Article Citation - WoS: 2Citation - Scopus: 22-Ag and Bone Marrow-Targeted Pcl Nanoparticles as Nanoplatforms for Hematopoietic Cell Line Mobilization(Bmc, 2024) Kose, Sevil; Varan, Cem; Onen, Selin; Nemutlu, Emirhan; Bilensoy, Erem; Korkusuz, PetekBackgroundThe use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated.MethodsPCL nanoparticles were prepared by using the emulsion evaporation method and characterized by Zetasizer and scanning electron microscopy (SEM). The encapsulation efficiency and release profile of 2-AG were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The presence of cannabinoid receptors (CBRs) in HSCs and monocytes was detected by flow cytometry. Cell morphology and viability were assessed using transmission electron microscopy (TEM), SEM, and the WST-1 viability assay. The migration efficacy of the 2-AG and 2-AG-loaded nanoparticle delivery system on HSCs and HPSCs (TF-1a and TF-1) and monocytes (THP-1) was evaluated using a transwell migration assay.ResultsThe 140-225 nm PCL nanoparticles exhibited an increasing polydispersity index (PDI) after the addition of Ps and 2-AG, with a surface charge ranging from - 25 to -50 mV. The nanoparticles released up to 36% of 2-AG within the first 8 h. The 2-AG-Ps-PCL did not affect cellular viability compared to control on days 5 and 10. The HSCs and monocytes expressed CB1R and CB2R and revealed increased migration to media containing 1 mu M 2-AG-Ps-PCL compared to control. The migration rate of the HSCs toward monocytes incubated with 1 mu M 2-AG-Ps-PCL was higher than that of the monocytes of control. The 2-AG-Ps-PCL formulation provided a real time mobilization efficacy at 1 mu M dose and 8 h time window via a specific CBR agonism.ConclusionThe newly generated and validated 2-AG-loaded PCL nanoparticle delivery system can serve as a stable, long lasting, targeted mobilization agent for HSCs and as a candidate therapeutic to be included in HSC transplantation (HSCT) protocols following scale-up in vivo preclinical and subsequent clinical trials.Article Citation - Scopus: 1Systemic Iodine Levels Increase With Povidone-Iodine Irrigation, but Does This Affect Thyroid Functions? a Case-Control Study(Bmc, 2024) Ertan, Mehmet Batu; Basarir, Kerem; Kocaoglu, Hakan; Aydugan, Mehmet Yagiz; Guengoer, ErdalBackgroundIntraoperative irrigation with diluted povidone iodine (PI) can be used to reduce the incidence of infection-related complications in arthroplasty surgeries. Since PI is associated with many interventions, especially skin antisepsis, its systemic effects are being studied. The aim of our study is to evaluate the systemic effects of PI, which we use as an irrigation solution, by means of urine iodine and thyroid function tests.MethodsIn this case-control study, 96 patients who underwent knee or hip arthroplasty were included and divided into two groups according to the irrigation solution. In the first group, PI was added to the standard irrigation. The second group was considered as the control group and only standard irrigation was applied. Urine iodine, thyroid stimulating hormone, free T3 and free T4 values were compared in the preoperative and postoperative periods of these two groups. In this way, the effect of absorbed iodine on thyroid functions was investigated.ResultsIn the diluted PI group, urinary iodine levels were measured at maximum levels (450 mu g/L) in the early postoperative period in most of the patients. The statistically significant difference in urinary iodine levels between the PI group and the control group, which started in the early postoperative period, continued until the last follow-up on the 14th postoperative day. In terms of thyroid functions, the observed differences were not statistically significant.ConclusionStudies to reduce periprosthetic infection show that PI can be preferred for irrigation before the closure of the joint area in total joint arthroplasty. Although the success of this treatment in periprosthetic infection has been investigated, its systemic examination has not been demonstrated. It was determined that PI treatment, which was seen to decrease in the systemic circulation within 14 days, did not show a statistically significant change in terms of thyroid functions when used at the determined concentration and duration. These results should be evaluated with larger and longer-term studies.Trial registrationClinical trials ID no. NCT05599841.Article Citation - WoS: 5Citation - Scopus: 6Adaptation of Food Craving Inventory To Turkish Culture: a Validity and Reliability Study(Bmc, 2022) Ozel, Irem Cagla; Yabanci Ayhan, Nurcan; Cetiner, OzlemPlain English Summary This study was carried out to adapt the Food Craving Inventory to Turkish. The English version of inventory consists of 4 sub-factors that measure cravings for high-fat foods, carbohydrates/starches, sweets, and fast food fats, and creates a total score. The sample of the study consists of 621 individuals between the ages of 19-50 who voluntarily agree to participate in an online survey. This study revealed that FCI-TR is a valid instrument of specific food cravings in the Turkish adult population. Turkish version of the FCI also consist of 4 sub-factors. Women experienced more food craving for sweets than men. While the most craved food by women was chocolate, men scored significantly higher on bread than women. In addition, a relationship was found between food craving and body weight. Introduction The Food Craving Inventory is a 28-item self-report measure of specific food cravings. The inventory consists of 4 factors: high fats, sweets, carbohydrates/starches and fast-food fats. Purpose This study was carried out to evaluate the Turkish validity and reliability of the Food Craving Inventory, and to determine the psychometric properties and factor structure of the Turkish version. Methods The sample of the study consists of 621 individuals between the ages of 19-50 who voluntarily agree to participate in online survey. Validity and reliability analyses were performed for the Turkish version of Food Craving Inventory (FCI-TR). Confirmatory factor analysis was performed to evaluate the factor structure of the Turkish version of FCI. Results Confirmatory factor analysis yielded a four-factor structure as "sweets," "high-fats," "carbohydrates/starches" and "fast food fats". The Cronbach-alpha coefficient for the total score was 0.84; subfactors were calculated as 0.74 for "sweets", 0.64 for "high-fat foods", 0.65 for "carbohydrates/starches", and 0.66 for "fast-food fats". The scores of the FCI-TR factors and its total score significantly correlated with the sub-factors of Three Factor Eating Questionnaire (TFEQ). A significant correlation was found between body mass index (BMI) and high fats and fast-food fats factor score. Also total and factor scores of the FCI-TR were different between BMI groups. Conclusions This study demonstrates that the Turkish version of the FCI is a valid and reliable tool to measure food cravings in the Turkish population. FCI is also correlated with sub-factors of TFEQ.

