Current Projects

Investigating the effect of plasma-derived extracellular vesicles on microchimeric cell traffic throughout the human placenta barrier

Microchimerism is the presence of less than 1% of allogeneic cells within an individual and characterized by a bidirectional exchange of cells (stem cells, leukocytes, among other cell types) controlled by the placenta from maternal to fetal tissues, resulting in maternal microchimerism, and vice versa, leading to fetal microchimerism. In humans, cells of fetal origin have been detected in maternal blood as early as the fourth week of gestation [2]. Extracellular vesicles (EVs) are lipid bilayer-delimited particles released from all organ cells and circulate in the body fluids. EVs can act as vehicles transporting information to the recipient cells or modifying the environment contributing to cell adaptations. In pregnancy, it was tested that placenta-derived EVs can reach the maternal periphery and target specific organs. In addition, it has been demonstrated the heterogeneous constitution of organ-specific EVs in the plasma being the adipose tissue, muscle, lung, and liver the main contributors [3]. The possibility that EVs composition may be implicated in the organ-specific microchimeric cell tropism needs further exploration. The presence of placenta-specific EVs in plasma may be implicated in the specific occurrence of microchimeric cells in pregnant women. Therefore, the project aims to investigate the potential contribution of EVs isolated from the plasma of pregnant women in the cell traffic through the placenta barrier in vitro.

References:

1. Murrieta-Coxca, J.M., et al., Synergies of Extracellular Vesicles and Microchimerism in Promoting Immunotolerance During Pregnancy. Front Immunol, 2022. 13: p. 837281.
2. Pertl, B. and D.W. Bianchi, First trimester prenatal diagnosis: fetal cells in the maternal circulation. Semin Perinatol, 1999. 23(5): p. 393-402.
3. Li, Y., et al., EV-origin: Enumerating the tissue-cellular origin of circulating extracellular vesicles using exLR profile. Comput Struct Biotechnol J, 2020. 18: p. 2851-2859.

The concept of PlacentAging refers to the aging process of the placenta during pregnancy. The placenta is a temporary organ that has a vital role in supporting the growth and development of the fetus. It undergoes changes and its function may be influenced by various factors including aging which is a condition associated with the progressive loss of tissue function over the lifetime and with an increased risk of age-associated pathologies. Although aging is conceived as a normal process in placenta development, advanced maternal age (AMA) may affect the aging process of the placenta. AMA is defined as being 35 years or older at the time of delivery and is associated with higher risks of pregnancy disorders and adverse perinatal outcomes. Therefore, premature placenta aging and abnormal placenta development may result in fertility complications. Although aging is a consequence of the interaction between environmental and genetic factors, other hallmarks play an important role. Among those elements, circulating cell-free mitochondrial DNA (ccf-mtDNA) is getting attention as critical in the regulation of senescence features in aging. It can be found in two conditions, membrane-bound and -unbound. The membrane-bound mtDNA is released encapsulated into cell-derived extracellular vesicles (EVs). This specific component, the release of mtDNA in EVs by trophoblast cells focuses on a molecular aspect of the placenta aging process. EVs harboring mtDNA could have implications for cellular communication and signaling within the placenta and it may be related to the overall aging and functional changes observed in the placenta during the course of pregnancy. A potential increase in membrane-bound mtDNA may contribute to the acceleration of senescence processes within the placenta. The compromised function of trophoblast cells is anticipated to manifest through diminished cell fusion, particularly in terms of trophoblast syncytialization, thereby indicating inadequate placental development associated with premature aging. Our further research in this area aims to understand molecular mechanisms involved in aging of the placenta and their impact on placental and fetal health.