Mesenchymal Stem Cell Secretome: Potential Applications in Human Infertility Caused by Hormonal Imbalance, External Damage, or Immune Factors

Mesenchymal stem cells (MSCs) are a source of a wide range of soluble factors, including different proteins, growth factors, cytokines, chemokines, and DNA and RNA molecules, in addition to numerous secondary metabolites and byproducts of their metabolism. MSC secretome can be formally divided into secretory and vesicular parts, both of which are very important for intercellular communication and are involved in processes such as angiogenesis, proliferation, and immunomodulation. Exosomes are thought to have the same content and function as the MSCs from which they are derived, but they also have a number of advantages over stem cells, including low immunogenicity, unaltered functional activity during freezing and thawing, and a lack of tumor formation. In addition, MSC pre-treatment with various inflammatory factors or hypoxia can alter their secretomes so that it can be modified into a more effective treatment. Paracrine factors secreted by MSCs improve the survival of other cell populations by several mechanisms, including immunomodulatory (mostly anti-inflammatory) activity and anti-apoptotic activity partly based on Hsp27 upregulation. Reproductive medicine is one of the fields in which this cell-free approach has been extensively researched. This review presents the possible applications and challenges of using MSC secretome in the treatment of infertility. MSCs and their secretions have been shown to have beneficial effects in various models of female and male infertility resulting from toxic damage, endocrine disorders, trauma, infectious agents, and autoimmune origin.