Adipose-Derived Mesenchymal Stem Cells: A Promising Tool in the Treatment of pre mature ovarian failure

Highlights

• Premature ovarian failure (POF) is among the most common diseases in women.

• Ovarian failure causes complications that can lead to infertility, though they have not been determined precisely and require further studies

• There are several treatments for POF, but none are definite because of the complexity of POF.

• One of the most effective treatments in this regard is the application of stem cells, which have received a lot of attention due to possessing unique self-renewal and proliferative features.

• Among stem cells, adipose-derived stem cells (ADSCs) are easier to obtain and are more abundant than other stem cells. They also increase Tregs in the body.

Abstract

Despite being rare, primary ovarian insufficiency (POI) is a significant cause of infertility and deficiency of ovarian hormone in women. Several health risks are also associated with POI, which include dry eye syndrome, reduced density of bones and enhanced fracture risks, troublesome menopausal symptoms, early development of cardiovascular disease, and psychological effects such as declined cognition, reduced perceived psychological support, anxiety, and depression. Replacing premenopausal levels of ovarian sex steroids through proper hormone replacement therapy could improve the quality of life for POI women and ameliorate related health risks. Herein, POI and its complications, in addition to hormone replacement therapies, which are safe and effective, are discussed. It is proposed that the use of HRT) Hormone replacement therapy (formulations which mimic normal production of ovarian hormones could reduce POI-associated morbidity rates if they are continued by the age 50, which is approximately the natural age of menopause. Particular populations of POI women are also addressed, which include those with enhanced risk of ovarian or breast cancer, those with Turner syndrome, those approaching natural menopause, and those who are breastfeeding. It is generally predicted that stem cell-based therapies would be both safe and effective. In fact, several types of cells have been described as safe, though their effectiveness and therapeutic application are yet to be defined. Several factors exist which could affect the results of treatment, such as cell handling, ex-vivo preparation strategies, variations in tissue of origin, potency, and immunocompatibility. Accordingly, cell types potentially effective in regenerative medicine could be recognized. Notably, products of MSCs from various sources of tissues show different levels of regenerative capabilities. The ultimate focus of the review is on adipose tissue-derive MCSs (ADMSCs), which possess exceptional features such as general availability, great ability to proliferate and differentiate, immunomodulatory capabilities, and low immunogenicity.

Introduction

Premature ovarian failure (POF) is among the most common diseases in women. This term refers to a condition in which the follicles in ovaries are destroyed or inactivated (Hoek et al., 1997; Kovanci & Schutt, 2015). Evidence with regards to the exact prevalence of POF do not exist yet. Almost 1% of women younger than 40 are estimated to be affected by spontaneous POF. Although particular information are lacking, the incidence of iatrogenic POF is increasing, which is concerning. As a result of increased survival rates following malignant diseases, more women now experience the long-term effects of treatments in this regard, including radiotherapy and chemotherapy (Maclaran & Panay, 2011).

Although the causes of ovarian failure have not been precisely identified, factors such as surgery, radiation or chemotherapy, genetic and chromosomal abnormalities, environmental factors (chemical agents, viruses, etc.), metabolic damage of ovarian autoimmunity (type 1 diabetes, galactosemia, deficiency of 17-OH and OH-21, etc.), endometriosis, and polycystic ovary syndrome are involved in the development of ovarian failure (Komorowska, 2016). Ovarian failure occurs with symptoms such as amenorrhea or infertility. However, comorbidities including hypotension, axillary and genital hair loss, hyperpigmentation or vitiligo (related to autoimmune adrenal insufficiency, thyroid enlargement, and exophthalmos can also be symptoms of ovarian failure (Ahonen et al., 1990; Betterle et al., 2002; Betterle & Volpato, 1998).

One of the recent treatment options for ovarian failure is the use of ADMSCs. Adipose tissue is totally available and is in fact a rich source for stem cells which possess multipotent characteristics that are proper for application in regenerative medicine and tissue engineering (Parhizkar et al., 2021). These are the reasons why ADMSCs have become popular among researchers (Bunnell et al., 2008).

Obtaining ADMSCs could be performed on adipose tissue using liposuction, washing, collagenase digestion, and centrifugation. The advantages of employing adipose stem cells over bone marrow cells include less invasion, facile application, and abundance of this tissue in the body (Aghlmandi et al., 2021). Reproduction, migration, and ADMSC differentiation can be regulated using estrogen. In this review, the causes of POF, effective treatment strategies, and the effect of Adipose-Derived Mesenchymal Stem Cell transplantation for the treatment of premature ovarian failure are reviewed.