Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625, Hannover, Germany.
Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625, Hannover, Germany.
Pediatr Res. 2023 Mar;93(4):810-817. doi: 10.1038/s41390-022-02165-x. Epub 2022 Jun 22.
Successful pregnancies are nowadays possible after kidney transplantation but are associated with a higher incidence of maternal and fetal complications. Immunosuppressive therapy causes cardiovascular side effects but must be maintained during pregnancy. Little is known about the consequences of maternal kidney transplantation on offspring's endothelial health. Endothelial colony forming cells (ECFCs) represent a highly proliferative subtype of endothelial progenitor cells and are crucial for vascular homeostasis, repair and neovascularization. Therefore, we investigated whether maternal kidney transplantation affects fetal ECFCs' characteristics.
ECFCs were isolated from umbilical cord blood of uncomplicated and post-kidney-transplant pregnancies and analyzed for their functional abilities with proliferation, cell migration, centrosome orientation and angiogenesis assays. Further, ECFCs from uncomplicated pregnancies were exposed to either umbilical cord serum from uncomplicated or post-kidney-transplant pregnancies.
Post-kidney-transplant ECFCs showed significantly less proliferation, less migration and less angiogenesis compared to control ECFCs. The presence of post-kidney-transplant umbilical cord serum led to similar functional aberrations of ECFCs from uncomplicated pregnancies.
These pilot data demonstrate differences in ECFCs' biological characteristics in offspring of women after kidney transplantation. Further studies are needed to monitor offspring's long-term cardiovascular development and to assess possible causal relationships with immunosuppressants, uremia and maternal cardiovascular alterations.
Pregnancy after kidney transplantation has become more common in the past years but is associated with higher complications for mother and offspring. Little is known of the impact of maternal kidney transplantation and the mandatory immunosuppressive therapy on offspring vascular development. In this study we are the first to address and detect an impairment of endothelial progenitor cell function in offspring of kidney-transplanted mothers. Serum from post-transplant pregnancies also causes negative effects on ECFCs' function. Clinical studies should focus on long-term monitoring of offspring's cardiovascular health.
如今，肾移植后成功妊娠已成为可能，但会增加母婴并发症的发生率。免疫抑制疗法会导致心血管副作用，但在妊娠期间必须维持该疗法。对于母体肾移植对后代内皮健康的影响，人们知之甚少。内皮祖细胞（endothelial progenitor cells，EPCs）中的集落形成细胞（colony forming cells，ECFCs）代表了一种高度增殖的内皮前体细胞亚型，对于血管稳态、修复和血管新生至关重要。因此，我们研究了母体肾移植是否会影响胎儿 ECFCs 的特征。
从无并发症和肾移植后妊娠的脐带血中分离 ECFCs，并用增殖、细胞迁移、中心体取向和血管生成测定等方法分析其功能能力。进一步，将无并发症妊娠的 ECFCs 暴露于无并发症或肾移植后妊娠的脐带血清中。
与对照 ECFCs 相比，肾移植后 ECFCs 的增殖、迁移和血管生成能力明显降低。肾移植后脐带血清的存在导致无并发症妊娠 ECFCs 的功能异常类似。
这些初步数据表明，肾移植后妇女的胎儿 ECFCs 生物学特征存在差异。需要进一步研究来监测后代的长期心血管发育，并评估与免疫抑制剂、尿毒症和母体心血管改变相关的可能因果关系。
近年来，肾移植后妊娠变得更为常见，但会增加母婴并发症的风险。对于母体肾移植和强制性免疫抑制治疗对后代血管发育的影响，人们知之甚少。在这项研究中，我们首次发现并检测到肾移植母亲后代的内皮祖细胞功能受损。移植后妊娠的血清也会对 ECFCs 的功能产生负面影响。临床研究应重点关注对后代心血管健康的长期监测。
