Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulatedin vitroto develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine.

This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSCs)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl₄ (1μL/g intraperitoneally) twice/week for 1 month. MSCs (1x10⁶), or MSC-conditioned medium (MSC-CM) were intravenously injected 24h after CCl₄ and on every 7^th day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining and RT-PCR. Serum levels of cytokines, IDO and kynurenine were determined by ELISA. Flow cytometry was performed to identify liver infiltrated cells. In vitro, CD4+ T cells were stimulated and cultured with MSCs. 1-methyltryptophan was used for inhibition of Indoleamine 2,3-dioxygenase (IDO). MSCs significantly attenuated CCl₄-induced liver fibrosis by decreasing serum levels of inflammatory IL-17, increasing immunosuppressive IL-10, IDO and kynurenine, reducing number of IL-17 producing Th17 cells and increasing percentage of CD4+IL-10+ T cells. Injection of MSC-CM resulted with attenuated fibrosis accompanied with the reduced number of Th17 cells in the liver, and decreased serum levels of IL-17. MSC-CM promoted expansion of CD4+FoxP3+IL-10+ T regulatory cells and suppressed proliferation of Th17 cells. This phenomenon was completely abrogated in the presence of IDO inhibitor. MSCs, in IDO dependent manner, suppress liver Th17 cells which lead to the attenuation of liver fibrosis.

Transplantation of mesenchymal stem cells (MSCs) reduces the severity of dextran sulphate sodium‐ (DSS‐) induced colitis. MSCs are able to secrete Galectin‐3 (Gal‐3), a protein known to affect proliferation, adhesion, and migration of immune cells. We investigate whether newly synthetized inhibitor of Gal‐3 (Davanat) will affect production of Gal‐3 in MSCs and enhance their potential to attenuate DSS‐induced colitis. Pharmacological inhibition of Gal‐3 in MSCs enhances their capacity to promote alternative activation of peritoneal macrophages in vitro and in vivo. Injection of MSCs cultured in the presence of Davanat increased concentration of IL‐10 in sera of DSS‐treated animals and markedly enhanced presence of alternatively activated and IL‐10 producing macrophages in the colons of DSS‐treated mice. Pharmacological inhibition of Gal‐3 in MSCs significantly attenuates concentration of Gal‐3 in sera of DSS‐treated animals, indicating that MSCs produce Gal‐3 in this disease. In conclusion, our findings indicate that Davanat could be used for improvement of MSC‐mediated polarization towards immunosuppressive M2 phenotype of macrophages.

It was once suggested that adult or tissue-specific stem cells may be immortal; however, several recently published data suggest that their efficacy is limited by natural aging in common with most other somatic cell types. Decreased activity of stem cells in old age raises questions as to whether the age of the donor should be considered during stem cell transplantation and at what age the donor stem cells should be harvested to ensure the largest possible number of viable, functional, and non-altered stem cells. Although stem cells remain active into old age, changes in stem cells and their microenvironments inhibit their regenerative potential. The impact of aging on stem cell populations differs between tissues and depends on a number intrinsic and extrinsic factors, including systemic changes associated with immune system alterations. In this review, we describe key mechanisms of stem and progenitor cell aging and techniques that are currently used to identify signs of stem cells aging. Furthermore, we focus on the impact of aging on the capacity for proliferation, differentiation, and clinical use of stem cells. Finally, we detail the aging of embryonic, mesenchymal, and induced pluripotent stem cells, with particular emphasis on aging mechanisms and rejuvenation.