Intraovarian administered BMSCs are able to restore ovarian hormone production and reactivate folliculogenesis in chemotherapy-induced ovarian failure mouse model.
Uterine fibroid(s) (UF/UFs) are benign tumors commonly found in women of reproductive age. The long-term outcomes of myomectomies are often hampered by high rates of recurrence (up to 60%).
Objective
To study whether efficient transduction and subsequent elimination of fibroid tumor initiating stem cells during debulking of tumor cells will aid in completely eradicating the tumor as well as decreasing the likelihood of recurrence.
Design
We have developed a localized non-surgical adenovirus-based alternative for the treatment of UFs. Combining viral based gene delivery with nanotechnology provides an opportunity to develop more efficient targeted viral gene therapy. Magnetic nanoparticles (MNPs) complexed to adenovirus, in the presence of an external magnetic field, accelerate adenovirus transduction.
Setting
Research laboratory located in Georgia Regents University, an academic research institution.
Patients N/A Interventions
MNPs complexed to adenovirus (AD GFP) or (AD LacZ) were used to transfect differentiated human fibroid cells in vitro. Main Outcome Measures rate of transduction and tumor growth inhibition.
Results
We observed a significant increase in transduction efficiency among differentiated human fibroid cells at 2 different multiplicities of infection (MOI); 1 and 10 respectively, with MNPs as compared to adenovirus-alone. Human fibroid stem cells transfected with AD-LacZ expressed β-Galactosidaze at (MOI) of 1, 10, and 50 at percentages of 19%, 62%, and 90%, respectively, which were significantly enhanced with MNPs.
Conclusion
When applied with adenovirus herpes simplex thymidine kinase, magnetofection significantly suppressed proliferation and induced apoptosis in both cell types. Through the use of magnetofection, we will prove that a lower viral dose will effectively increase the overall safety profile of suicide gene therapy against fibroid tumors.
Background: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. Materials and Method: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions. The second was to prove improved fertility. A total of 36 mice were randomly assigned; 6 mice into each of 3 groups for two experiments. Group 1 (control), group 2 (sham chemotherapy), group 3 (stem cells). Results: In the first experiment, post-UCMSCs treatment (group 3) showed signs of restored ovarian function in the form of increased ovarian weight and estrogen-dependent organs (liver, uterus), increased follicular number, and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 versus group 2. Immuno-histochemistry analysis demonstrated a higher expression of AMH, follicle stimulating hormone receptor (FSHR) and Inhibin A in the growing follicles of group 3 versus group 2. In the second experiment, post-UCMSCs treatment (group 3) pregnancy rates were higher than group 2, however, they were still lower than group 1. Conclusion: We demonstrated the ability of UCMSCs to restore fertility in female cancer survivors with POI and as another source of stem cells with therapeutic potentials.
Trichomoniasis is the most common curable sexually transmitted disease worldwide. Resistance to metronidazole in treating trichomoniasis is a problematic health issue. We aimed to determine the minimum lethal concentration (MLC) of metronidazole for Trichomonas vaginalis isolates detected in Mansoura, Egypt and studied the genotypic profile of these isolates. Vaginal swab specimens were obtained from 320 symptomatic and 100 asymptomatic females, for whom clinical examination, vaginal discharge wet mount, Giemsa stain, and culture in modified Diamond's media were performed. Metronidazole susceptibility testing by an aerobic tube assay was performed. Both sensitive and resistant isolates were examined by PCR amplification followed by restriction fragment length polymorphism (RFLP). Trichomonas vaginalis was identified in 49/420 (11.7%) using either culture or PCR, while wet mount and Giemsa stain detected the parasite in 8.1 and 7.6% of participants, respectively. After 48 h incubation, most isolates were sensitive to metronidazole with a minimal lethal concentration (MLC) of 1 μg/ml. Mild resistance was observed in two isolates with MLCs of 64 μg\ml and mild to moderate resistance was observed in an additional two isolates with MLCs of 128 μg/ml. The four isolates that demonstrated low to moderate metronidazole resistance displayed a unique genotype band pattern by RFLP compared to the other 45 samples that were metronidazole sensitive. Our results highlight the presence of in vitro metronidazole tolerance in a few T. vaginalis isolates in Mansoura, Egypt that may lead to the development of drug resistance as well as the possibility of an identifying RFLP pattern in the isolates.
Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial.
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