Biomedical Research and Therapy 2023, 10(6):5744-5756 Open Access Full Text Article Review 1 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Islamic Azad University, Tehran Medical Branch, Tehran , Iran Correspondence Maryam Salimi, Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Email: m.salimi87@yahoo.com Correspondence Elham Roshandel, Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Email: elham.roshandel@gmail.com History • Received: Apr 03, 2023 • Accepted: May 29, 2023 • Published: Jun 30, 2023 DOI : 10.15419/bmrat.v10i6.815 Mesenchymal stem cell transplantation for infertility treatment: A review Reza Mirfakhraie 1,2 , Maryam Vahdat Lasemi 1 , Maryam Mehravar 1 , Dorsa Halvachi 3 , Maryam Salimi 1,* , Elham Roshandel 1,* Use your smartphone to scan this QR code and download this article ABSTRACT Infertility is a global disorder is resulted from factors related to men or women and afects not only the individual, but also the family and society. Recently, stem cell-based therapy, known as regen- erative medicine, uses stem cells or their derivatives to treat diseases, promising new ways to treat infertility. Several in vitro studies as well as studies on animal models, confrm the role of Mesenchy- mal stem cells (MSC), a kind of multipotent stem cells, in the recovery of folliculogenesis and sper- matogenesis. MSCs play the role of therapeutic efect in infertility from two basic aspects including regenerative medicine through diferentiation and paracrine pathway via participating in cell hom- ing, immune regulation, and the secretion of active factors and exosomes. Furthermore, there are fewer ethical concerns about using MSCs compared to other source of stem cells like embryonic stem cells. Here we discuss therapeutic approaches of diferent sources of MSC to restore fertility, then the basic aspects related to their paracrine efects will be described in detail. Finally, methods of MSCs delivery in clinical trials for treatment of infertility-related disorders will be mentioned. But before all these, frst we will talk about pros and cons of MSC therapy. Key words: Stem cell therapy, Mesenchymal stem cell, Infertility Treatment INTRODUCTION Infertility is a social health problem afecting both men and women and is defned as the inability to be- come pregnant afer at least one year of unprotected sex 1 . Various factors afect couples’ fertility, includ- ing genetic factors, anatomical defects, and environ- mental elements 2 . Some major reproductive disorders causing female in- fertility include uterine abnormalities, ovulatory dis- orders, a history of tubal pregnancy, and abnormal menstruation 3 . According to WHO, uterine abnor- malities include intrauterine adhesion (IUA; Asher- man syndrome [AS]), endometriosis, uterine polyps, and uterine fbroids 4 . Ovulatory disorders include premature ovarian insufciency (POI) and polycystic ovary syndrome (PCOS) 5 . Similarly, since several factors cause male infertility, problems in males are responsible for almost half of all infertility cases. Tese factors include hypogonadism (causing low blood testosterone levels), undescended testicles, injured testicles, testicular cancer, varicocele, premature ejaculation, and azoospermia 6,7 . Some common genetic factors also cause infertility, including Turner syndrome, Klein–Felter syndrome, deletion of the azoospermia factor c region of the Y chromosome, fragile X syndrome, androgen recep- tor (AR) mutations (e.g., CAG repeat expansion), and cystic fbrosis 8,9 . While conventional therapies such as ovulation med- ications or assisted reproductive technology are ef- fective for treating infertility, they have some limi- tations 10 . Terefore, recent studies have focused on evaluating newer methods to treat infertility, such as stem cell transplantation. Stem cells are self-sustaining cells in an organism that can diferentiate into various cell types. Several types of stem cells can be used for diferent purposes 11 . Embryonic stem cells (ESCs) are among the most widely used stem cells and can generate diferenti- ated cells with some germ-cell markers. However, their use has disadvantages, such as ethical concerns (destruction of human embryos) and tumor forma- tion 12 . Terefore, mesenchymal stem cells (MSCs), a new source of stem cells, are an alternative option for infertility treatment. Tese spindle-shaped cells orig- inate from various tissues and diferentiate into cells related to all three germ layers 13 . Since growth fac- tors secreted by MSCs are involved in survival, prolif- eration, migration, immunomodulation, and angio- genesis, they have become ideal options for regener- ative medicine 14 . Te biological properties of MSCs enable them to regulate immunological mechanisms and contribute to the restoration of the ovaries, ovar- ian tissue, and uterus. MSCs can also positively afect Cite this article : Mirfakhraie R, Lasemi M V, Mehravar M, Halvachi D, Salimi M, Roshandel E. Mesenchymal stem cell transplantation for infertility treatment: A review. Biomed. Res. Ther.; 2023,10(6):5744-5756. 5744 Copyright © Biomedpress. This is an open- access article distributed under the terms of the Creative Commons Attribution 4.0 International license.