Advances in Stem Cell Treatment of Gynaecological Conditions

Written by Dr. Lana du Plessis, Laboratory Director at CryoSave

In recent years studies have shown the potent regenerative effect of stem cell therapy in gynecologic diseases such as infertility, Asherman syndrome, lichen sclerosus, polycystic ovary syndrome, premature ovarian insufficiency, genitourinary syndrome of menopause, and rectovaginal fistulas.

Infertility is one of the world’s most common gynecological disorders. It is the inability to conceive after six months of regular intercourse if the woman is older than 35 years of age or 12 months if she is younger than 35 years of age. In recent advances, mesenchymal stromal cells have shown improved clinical outcomes for the treatment of infertility and are being used for clinical purposes but also their exosomes and mitochondria. MSC mitochondria are being used to improve oocyte quality (1).

Another great source for treating infertility is Menstrual Blood-MSCs. Men-MSCs also have an endometrial origin, which is why they can be a good replacement. With the help of estrogen and progesterone, they rebuild endometrial tissue in vivo after differentiation into endometrial cells in vitro. It was also shown that infertility could be characterized by the expression of CD9, CD44, CD73, CD90, and CD166 markers. It has been shown that infertile women have higher expression of surface markers CD56 and SUSD2 on their Men-MSCs. Therefore, Men-MSCs can be used as ideal regenerative cells for treatment purposes such as endometrial repair in patients with intrauterine adhesions, improvement in ovarian functions in those with premature ovarian failure, and repair of patients with pelvic organ prolapse (2).

Asherman syndrome is often a trauma-linked condition. It occurs when the basal layer of the endometrium is damaged either by physical trauma or after dilation and curettage. Autologous Men-MSCs were successfully isolated and expanded from menstrual blood and transplanted into the uterus of each patient, followed by hormonal stimulation. After 14 days of the transplantation transvaginal ultrasound, there was an improvement in the endometrial thickness: 3.9 ± 0.9 to 7.5 ± 0.6 mm (p < 0.001). Five patients achieved pregnancy, four after embryo transfers, and one from natural conception.

Polycystic ovary syndrome (PCOS) is a pervasive endocrine disorder that affects millions of women globally, impacting their hormonal balance, fertility and overall well-being. It is notoriously difficult to treat, with widely varying symptoms and mysterious, complex underlying causes. Recently published results demonstrate the promise of this novel therapeutic approach that uses mesenchymal stem cell-derived extracellular vesicles (EVs), also known as exosomes: tiny, free-floating packages of molecules released by stem cells (3).

Premature ovarian insufficiency (POI), also known as premature ovarian failure (POF), is a complex endocrine disease that commonly affects women under the age of 40. It is characterized by the cessation of ovarian function before the age of 40, leading to infertility and hormonal imbalances. However, there is currently no clear and effective treatment option for POI to restore ovarian function and infertility, and only a few preliminary studies have been undertaken. Since the introduction of iPSC technology more than a decade ago, it has now opened up a new direction to develop reproductively functional germ cells and their subsequent oocytes from pluripotent cells with the capability to restore fertility (4).

Genitourinary atrophy, previously known as vulvovaginal atrophy (VVA) or urogenital atrophy, nowadays called genitourinary syndrome of menopause (GSM), is a syndrome characterized by a lack of estrogen and therefore vaginal dryness, dyspareunia, often vulvovaginitis (VV), cystitis, urinary incontinence, burning, itching, stranguria, lesser sensitivity, etc. The vaginal microbiota is very important for women’s gynecologic and reproductive health and acts by preventing colonization by pathogenic organisms, including sexually transmitted and urinary tract infectious agents. eRecent research have indicated that MSC may provide the longest-lasting therapy, in comparison to other therapies and since there were no side-effects described from using MSC therapy, this type of therapy is deemed, completely safe as well (5).?

Many other diseases such as Lichen Sclerosus (LS), Rectovaginal Fistulas, to name but have been investigated to improve these conditions with the use of stem cells and many have shown improvement. Thus, even oogonial stem cells (OSCs), by successful isolation of OSCs could lead to a revolution in the field of gynecology and the potential treatment of many conditions?in this field.

In conclusion, new research has demonstrated the enormous therapeutic potential of stem cells for the management of a range of gynecological conditions. Numerous studies, including those conducted in human clinical trials and animal models, have demonstrated the safety, potential long-term benefits, and multimodal benefits of mesenchymal stem cells, including regenerative, angiogenic, immunomodulatory, analgesic, and antimicrobial (anti-inflammatory) effects. The application of stem cells, particularly MSCs, in gynecology and medicine as a whole is highly promising because of their high efficiency, safety, and potential for broad use in a variety of difficult cases and complex disorders that have not yet been successfully and durably treated. Further research is required to ascertain the precise manner in which they affect the human body, standardize the kind and amount required, and make applications more accessible to everyone.

References:

1. Skliute G., Bausyte R., Borutinskaite V., Valiuliene G., Kaupinis A., Valius M., Ramasauskaite D., Navakauskiene R. Menstrual Blood-Derived Endometrial Stem Cells’ Impact for the Treatment Perspective of Female Infertility. Int. J. Mol. Sci. 2021;22:6774. doi: 10.3390/ijms22136774
2. Lv Q., Wang L., Luo X., Chen X. Adult stem cells in endometrial regeneration: Molecular insights and clinical applications.?Mol. Reprod. Dev.?2021;88:379–394. doi:?10.1002/mrd.23476
3. Park HS, Cetin E, Siblini H, Seok J, Alkelani H, Alkhrait S, Liakath Ali F, Mousaei Ghasroldasht M, Beckman A, Al-Hendy A. Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles to Treat PCOS. Int J Mol Sci. 2023 Jul 6;24(13):11151
4. Ali I, Padhiar AA, Wang T, He L, Chen M, Wu S, Zhou Y, Zhou G. Stem Cell-Based Therapeutic Strategies for Premature Ovarian Insufficiency and Infertility: A Focus on Aging. Cells. 2022 Nov 22;11(23):3713
5. Casarotti G., Tremolada C. A new treatment of genito-urinary post-menopausal atrophy with autologous micro-fragmented fat tissue: A thirty-six months follow up case series.?Eur. Rev. Med. Pharmacol. Sci.?2020;24:7420–7426.