During pregnancy, a successful coexistence between the mother and the semi-allogenic fetus occurs which requires a dynamic immune system to guarantee an efficient immune protection against possible infections and tolerance toward fetal antigens. The mechanism of fetal-maternal tolerance is still an open question. There is growing in vitro and in vivo evidence that mesenchymal stromal cells (MSC) which are present in perinatal tissues have a prominent role in generating a functional microenvironment critical to a successful pregnancy. This review highlights the immunomodulatory properties of perinatal MSC and their impact on the major immune cell subsets present in the uterus during pregnancy, such as natural killer cells, antigen-presenting cells (macrophages and dendritic cells), and T cells. Here, we discuss the current understanding and the possible contribution of perinatal MSC in the establishment of fetal-maternal tolerance, providing a new perspective on the physiology of gestation.

Molecular biomarker profiling is an emerging field in maternal-fetal health with the potential to transform early detection and prediction of placental dysfunction. By analysing a range of biomarkers in maternal blood, researchers and clinicians can gain crucial insights into placental health, enabling timely interventions to enhance fetal and maternal outcomes. Placental structural function is vital for fetal growth and development, and disruptions can lead to serious pregnancy complications like preeclampsia. While conventional methods such as ultrasound and Doppler velocimetry offer valuable information on fetal growth and blood flow, they have limitations in predicting placental dysfunction before clinical signs manifest. In contrast, molecular biomarker profiling can provide a more comprehensive assessment by measuring proteins, metabolites, and microRNAs (miRNAs) in maternal blood, reflecting the placenta’s endocrine and metabolic functions. This approach offers a deeper understanding of placental health and function, aiding in early detection and prediction of complications. Challenges in developing molecular biomarker profiling include pinpointing specific molecular changes in the placenta linked to pathologies, timing predictions of conditions before clinical onset, and understanding how placental dysfunction affects maternal metabolism. Validating specific biomarkers and integrating them effectively into clinical practice requires further research. This review underscores the significance of molecular biomarker profiling as a powerful tool for early detection and prediction of placental dysfunction in maternal-fetal health. Through an exploration of biomarker analysis, we delve into how a deeper understanding of placental health can potentially improve outcomes for both mother and baby. Furthermore, we address the critical need to validate the utility of biomarkers and effectively integrate them into clinical practice.

The pathophysiology of preeclampsia (PE) is poorly understood; however, there is a large body of evidence that suggests a role of immune cells in the development of PE. Amongst these, B cells are a dominant element in the pathogenesis of PE, and they have been shown to play an important role in various immune-mediated diseases, both as pro-inflammatory and regulatory cells. Perinatal cells are defined as cells from birth-associated tissues isolated from term placentas and fetal annexes and more specifically from the amniotic membrane, chorionic membrane, chorionic villi, umbilical cord (including Wharton’s jelly), the basal plate, and the amniotic fluid. They have drawn particular attention in recent years due to their ability to modulate several aspects of immunity, making them promising candidates for the prevention and treatment of various immune-mediated diseases. In this review we describe main findings regarding the multifaceted in vitro and in vivo immunomodulatory properties of perinatal cells, with a focus on B lymphocytes. Indeed, we discuss evidence on the ability of perinatal cells to inhibit B cell proliferation, impair B cell differentiation, and promote regulatory B cell formation. Therefore, the findings discussed herein unveil the possibility to modulate B cell activation and function by exploiting perinatal immunomodulatory properties, thus possibly representing a novel therapeutic strategy in PE.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammation in the synovial tissue, driven by aberrant activation of both the innate and adaptive immune systems, which can lead to irreversible disability. Despite the increasing therapeutic approaches for RA, only a low percentage of patients achieve sustained disease remission, and the persistence of immune dysregulation is likely responsible for disease recurrence once remission is attained. Cell therapy is an attractive, wide-spectrum strategy to modulate inflammation, and mesenchymal stromal cells (MSC) derived from perinatal tissues provide valuable tools for their use in regenerative medicine, mainly due to their immunomodulatory properties. Several in vitro studies have shown that perinatal MSC modulate the proliferation, maturation, and cytokine secretion profile of both innate and adaptive immune cells. Moreover, different beneficial effects have also been described when perinatal MSC were used to treat animal models of diseases associated with inflammatory conditions and degenerative processes. Specifically, in experimental models of RA, treatment with perinatal MSC resulted in a strong reduction of articular damage, which was associated with the modulation of both inflammation and activation of stromal resident cells in the synovial tissue. Here, we present in vitro and in vivo evidence supporting the use of perinatal MSC in RA. We also highlight the promising results from the few published clinical trials, which demonstrate the safety of perinatal MSC.