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.
Scientists from multiple basic disciplines and an international group of physician-scientists from the fields of obstetrics and gynecology presented recent studies and discussed new and evolving theories of uterine fibroid etiology, growth, and development at the Basic Science of Uterine Fibroids meeting, sponsored by the Campion Fund and the National Institute of Environmental Health Sciences. The purpose was to share up-to-date knowledge and stimulate new concepts regarding the basic molecular biology and pathophysiology of uterine fibroids and promote future collaborations. The meeting was held at the National Institutes of Environmental Health Sciences
Somatic stem cells (SSCs) are defined as a rare population of undifferentiated cells residing in differentiated tissues and organs. Different studies and diverse approaches suggest the presence of SSCs in human and murine endometria. Owing to the lack of specific phenotypic markers to identify endometrial SSCs, they are defined by their functional properties. The embryological origin of the uterus and the putative implication of bone marrow in endometrial regeneration suggest their presumed mesenchymal origin. Nevertheless, more information is needed regarding the physiology of endometrial stem cells to understand the gynecological disorders associated with abnormal endometrial proliferation, such as endometriosis and endometrial cancer.
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