**3. Conclusions**

the annual trials registered and many of the trials were in the early phase of development (phase I or II). The cells from the amniotic membrane and placental tissue seem to be in a growth period for clinical trials. It will be important to track the progress of these trials and

**Figure 6.** A search on ClinicalTrials.gov with the search terms mesenchymal stem cells illustrating the much greater

**Figure 5.** A narrow search on ClinicalTrials.gov with the search terms placenta derived cells illustrating the diverse

see which cells work in which indications.

numbers of clinical studies.

diseases investigated.

20 Placenta

In this chapter, the observation of fetal-maternal microchimerism that can last for decades indicated that the placenta exhibited highly specific and strong immune tolerance to the host. In an attempt to explain the immune tolerance mechanisms, we highlighted several cell types from Tregs to dendritic cells and their interactions with placental derived cells using in vitro and in vivo models. There were several molecular mechanisms (examples, IDO, PGE2, T cell proliferation, and DC maturation) invoked to explain some of the interactions with T cells and dendritic cells, which included the effects of cytokine secretion on the activation and differentiation status of immune cells. The in vitro and in vivo data describe a broad array of immune modulation functions suggesting that cells of placental origin have immune modulatory and immune tolerance inducing properties that are independent of tissue source.

These immune modulatory properties highlight some of the possible ways in which the physiology of the placental graft is maintained during pregnancy and well after for microchimerism. To put these interesting results into some physiological context, a recent example of the immune system driving preterm labor described a pro-inflammatory environment at the fetal-maternal interface as a prerequisite for preterm labor [31]. In this study, the authors demonstrated that fetal T cells produced INF-γ and TNF-α which preceded myometrial cell contraction required for parturition. In addition, the authors demonstrated that fetal T cells (both CD4 and CD8) specifically proliferated in response to maternal antigen. It is interesting to speculate that the placental MSC present at the fetal-maternal interface could participate in suppressing the pro-inflammatory signals and the T cell proliferation that drive preterm labor.

This is a very active field of clinical and pre-clinical investigation and has generated huge excitement in the field of advanced cell therapy. The near future will bring us clinical results that allow the advancement of cell therapy to FDA approval and ultimately for the benefit of the patients that eagerly await these therapies.
