“Adipose-derived mesenchymal stem cell therapy for the management of female sexual dysfunction: Literature reviews and study design of a clinical trial”

Abstract

Hormone imbalance and female sexual dysfunction immensely affect perimenopausal female health and quality of life. Hormone therapy can improve female hormone deficiency, but long-term use increases the risk of cardiovascular diseases and cancer. Therefore, it is necessary to develop a novel effective treatment to achieve long-term improvement in female general and sexual health. This study reviewed factors affecting syndromes of female sexual dysfunction and its current therapy options. Next, the authors introduced research data on mesenchymal stromal cell/mesenchymal stem cell (MSC) therapy to treat female reproductive diseases, including Asherman’s syndrome, premature ovarian failure/primary ovarian insufficiency, and vaginal atrophy. Among adult tissue-derived MSCs, adipose tissue-derived stem cells (ASCs) have emerged as the most potent therapeutic cell therapy due to their abundant presence in the stromal vascular fraction of fat, high proliferation capacity, superior immunomodulation, and strong secretion profile of regenerative factors. Potential mechanisms and side effects of ASCs for the treatment of female sexual dysfunction will be discussed. Our phase I clinical trial has demonstrated the safety of autologous ASC therapy for women and men with sexual hormone deficiency. We designed the first randomized controlled crossover phase II trial to investigate the safety and efficacy of autologous ASCs to treat female sexual dysfunction in perimenopausal women. Here, we introduce the rationale, trial design, and methodology of this clinical study. Because aging and metabolic diseases negatively impact the bioactivity of adult-derived MSCs, this study will use ASCs cultured in physiological oxygen tension (5%) to cope with these challenges. A total of 130 perimenopausal women with sexual dysfunction will receive two intravenous infusions of autologous ASCs in a crossover design. The aims of the proposed study are to evaluate 1) the safety of cell infusion based on the frequency and severity of adverse events/serious adverse events during infusion and follow-up and 2) improvements in female sexual function assessed by the Female Sexual Function Index (FSFI), the Utian Quality of Life Scale (UQOL), and the levels of follicle-stimulating hormone (FSH) and estradiol. In addition, cellular aging biomarkers, including plasminogen activator inhibitor-1 (PAI-1), p16 and p21 expression in T cells and the inflammatory cytokine profile, will also be characterized. Overall, this study will provide essential insights into the effects and potential mechanisms of ASC therapy for perimenopausal women with sexual dysfunction. It also suggests direction and design strategies for future research.

The Concept behind the Suitability of Menstrual Blood-Derived Stem Cells for the Management of Vaginal Atrophy among BRCA Mutation Carriers after RRSO

“…Not enough research has been conducted on the adverse reactions of MenSC-based therapy, and whether malignant transformation will occur after autologous transplantation. Nonetheless, a meta-analysis based on 62 prospective studies about the adverse events after MSC administration showed no association between this therapy and cancer or mortality incidence, and this analysis reported transient fever as the most common major side effect [55,56]. For this reason, robust evidence on this issue is mandatory in order to consider MenSC as a suitable therapy weapon for vaginal atrophy in patients with a predisposition to malignant disease, such as BRCA mutation carriers.…”

“…However, the optimal cryopreservation protocol is still under development and the long-term viability of cryo-MenSC should be carefully evaluated. To date, there are no more than 10 clinical trials registered exploring the MenSC role in regenerative medicine, but none is related to the potential use of these stem cells in vaginal atrophy [55].…”

“…To date, there are no more than 10 clinical trials registered exploring the MenSC role in regenerative medicine, but none is related to the potential use of these stem cells in vaginal atrophy [55].…”

Research progress on the premature ovarian failure caused by cisplatin therapy

“…Nierestrol can reduce the end-metabolism of lipid peroxides in vivo ( 39 ). The decrease in the hydroxyl radical levels and the increase in SOD activity can help protect the ovarian function and reduce the toxic effect of chemotherapeutic drugs.…”

Low-intensity pulsed ultrasound in obstetrics and gynecology: advances in clinical application and research progress

“…In addition, mesenchymal stem cell (MSC) transplantation is an effective treatment for POF and has been shown to restore ovarian structure and function in animal models ( 14 ). Human amnion-derived mesenchymal stem cells (hAD-MSCs) have been shown to possess the characteristics of MSC ( 15 ).…”