Llorente Vicente, López-Olañeta Marina, Blázquez-López Elena, Vázquez-Ogando Elena, Martínez-García Magdalena, Vaquero Javier, Carmona Susana, Desco Manuel, Lara-Pezzi Enrique, Gómez-Gaviro María Victoria
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Front Cell Dev Biol. 2024 Aug 5;12:1390533. doi: 10.3389/fcell.2024.1390533. eCollection 2024.
Multiple complex biological processes take place during pregnancy, including the migration of fetal cells to maternal circulation and their subsequent engraftment in maternal tissues, where they form microchimerisms. Fetal microchimerisms have been identified in several tissues; nevertheless, their functional role remains largely unknown. Different reports suggest these cells contribute to tissue repair and modulate the immune response, but they have also been associated with pre-eclampsia and tumor formation. In the maternal heart, cells of fetal origin can contribute to different cell lineages after myocardial infarction. However, the functional role of these cells and their effect on cardiac function and repair are unknown. In this work, we found that microchimerisms of fetal origin are present in the maternal circulation and graft in the heart. To determine their functional role, WT female mice were crossed with male mice expressing the diphtheria toxin (DT) receptor. Mothers were treated with DT to eliminate microchimerisms and the response to myocardial infarction was investigated. We found that removal of microchimerisms improved cardiac contraction in postpartum and post-infarction model females compared to untreated mice, where DT administration had no significant effects. These results suggest that microchimerisms play a detrimental role in the mother following myocardial infarction.
孕期会发生多种复杂的生物学过程,包括胎儿细胞向母体循环的迁移及其随后在母体组织中的植入,在这些组织中它们形成微嵌合体。已在多种组织中鉴定出胎儿微嵌合体;然而,它们的功能作用在很大程度上仍不清楚。不同的报告表明,这些细胞有助于组织修复并调节免疫反应,但它们也与子痫前期和肿瘤形成有关。在母体心脏中,胎儿来源的细胞在心肌梗死后可分化为不同的细胞谱系。然而,这些细胞的功能作用及其对心脏功能和修复的影响尚不清楚。在这项研究中,我们发现母体循环中存在胎儿来源的微嵌合体,并且它们会植入心脏。为了确定它们的功能作用,将野生型雌性小鼠与表达白喉毒素(DT)受体的雄性小鼠杂交。给母鼠注射DT以消除微嵌合体,并研究其对心肌梗死的反应。我们发现,与未处理的小鼠相比,消除微嵌合体可改善产后和心肌梗死后模型雌性小鼠的心脏收缩功能,而注射DT对未处理小鼠没有显著影响。这些结果表明,微嵌合体在心肌梗死后的母体中起有害作用。