Ovarian function and implantation of embryo are critical factors in pregnancy. So, their optimal conditions and tightly regulated networks are necessary in pregnancy as well as fetal development. However, there are limit approach to cure ovarian dysfunction or improve implantation rate despite of the development of associated reproductive technologies. Recently, translational studies have been explored the therapeutic effect of stem cells in reproductive medicine. Placenta derived mesenchymal stem cells (PD-MSCs) have been reported as alternative cell source capable of overcoming the limitation of bone marrow derived MSCs (BM-MSCs) and adipose-derived MSCs (AD-MSCs), which have stemness dependent by donor age as well as invasive procedure. In addition, their activities for self-renewal and immunomodulation were higher than those of others. In this section, we will review the stem cell therapy in reproductive medicine and introduce feasibilities of PD-MSCs on a rat model with ovarian failure as well as on trophoblast invasion activity. Finally, we introduce new insights into further understanding of stem cell-based therapeutic mechanisms for reproductive system as well as new avenues to develop more efficient therapies in degenerative medicine.

The trophectoderm is one of the earliest cell types to differentiate in the forming placenta. It is an important for the initial implantation and placentation during pregnancy. Trophoblast stem cells (TBSCs) develop from the blastocyst and are maintained by signals emanating from the inner cell mass. However, several limitations including rarity and difficulty in isolation of trophoblast stem cells derived from blastocyst still exist. To establish a model for trophoblast differentiation, we isolated TBSCs from human term placenta (38 weeks) and characterized. Cell cycle was analyzed by measuring DNA content by FACS analysis and phenotype of TBSCs was characterized by RT-PCR and FACS analysis. TBSCs have expressed various markers such as self-renewal markers (Nanog, Sox2), three germ layer markers (hNF68, alpha-cardiac actin, hAFP), trophoblast specific markers (CDX-2, CK7, HLA-G), and TERT gene. In FACS analysis, TBSCs isolated from term placenta showed that the majority of cells expressed CD13, CD44, CD90, CD95, CD105, HLA-ABC, cytokeratin 7, and HLA-G. Testing for CD31, CD34, CD45, CD71, vimentin and HLA-DR were negative. TBSCs were shown to decrease the growth rate when cultured in conditioned medium without FGF4/heparin as well as the morphology was changed to a characteristic giant cell with a large cytoplasm and nucleus. In invasion assay, TBSCs isolated from term placenta showed invasion activities in in vivo using nude mice and in vitro Matrigel system. Taken together, these results support that an isolation potential of TBSCs from term placenta as well as a good source for understanding of the infertility mechanism.

Implantation of the blastocyst into the maternal endometrium, mediated by well-differentiated primary cells of the placenta known as trophoblasts, grow in an invasive via complicated interaction with immune cells in the maternal myometrium. Placenta-derived stem cells (PDSCs), which is a fetal origin, display multi-lineages differentiation potential, and they are free of ethical concerns, easily accessible, abundant, and strongly immunosuppressive. However, the efficiency of PDSCs according to trophoblast invasion or immune modulation in implantation has not yet been evaluated. Here, we investigated the effects of PDSCs for trophoblast invasion as well as their potential for immune modulation of activated T cells when they co-cultured with PDSCs. Activated T cells and HTR-8SV/neo trophoblast cells were co-cultured with PDSCs according to cell dose-dependent manner. Activities for proliferation of T cells were analyzed by BrdU incorporation assay and cell invasions were estimated. Activation of T cells was significantly decreased in the group co-cultured with PDSCs comparing to normal fibroblast cells (p<0.05). In addition, trophoblast invasion by PDSCs have recorded a twofold increase than the normal fibroblast cells. These results contribute to our understanding of the potential roles of PDSCs, including immune modulation effects for trophoblast invasion in pregnancy, and provide a foundation for the development of new cell therapy-based strategies for the treatment of women with implantation.