Kennedy Institute of Rheumatology, Imperial College London, Hammersmith Campus, London, UK.
Cells Tissues Organs. 2011;193(6):379-92. doi: 10.1159/000321172. Epub 2010 Dec 11.
Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where they persist in tissue decades later. We investigated in mice whether fetal microchimeric cells (FMCs) can be detected in maternal kidney, and whether they play a role in kidney homeostasis. FMCs were identified in vivo in two models: one an adaptive model following unilateral nephrectomy, the other an injury via unilateral renal ischaemia reperfusion. Both models were carried out in mothers that had been mated with transgenic mice expressing luciferase transgene under the control of collagen type I, and had given birth to either 1 or 3 litters. FMCs were detected by Y-probe fluorescent in situ hybridization (FISH) and bioluminescence, and the cell number quantified by real-time polymerase chain reaction. In the adaptive model, the remaining kidney showed more cells by all 3 parameters compared with the nephrectomized kidney, while ischaemia reperfusion resulted in higher levels of FMC participation in injured compared to contralateral kidneys. Bioluminescence showed that FMCs switch on collagen type I transcription implicating mesenchymal lineage cells. After injury, Y-probe in situ hydridization was found mainly in the tubular epithelial network. Finally, we compared FMCs with bone marrow cells and found similar dynamics but altered distribution within the kidney. We conclude that FMCs (1) are long-term sequelae of pregnancy and (2) are recruited to the kidney as a result of injury or adaptation, where they activate the transcriptional machinery of matrix proteins.
胎儿细胞从妊娠早期第一 trimester 开始进入母体循环，并在数十年后仍存在于组织中。我们在小鼠中研究了胎儿微小嵌合体细胞（Fetal microchimeric cells，FMCs）是否能在母体肾脏中被检测到，以及它们是否在肾脏稳态中发挥作用。我们在两种模型中体内鉴定了 FMCs：一种是单侧肾切除后的适应性模型，另一种是单侧肾缺血再灌注损伤模型。这两种模型都是在与表达荧光素酶转基因的雄性小鼠交配并生育 1 或 3 窝后代的母鼠中进行的。FMCs 通过 Y 探针荧光原位杂交（Fluorescent in situ hybridization，FISH）和生物发光检测，并通过实时聚合酶链反应（Polymerase chain reaction，PCR）定量细胞数量。在适应性模型中，与肾切除侧相比，剩余肾脏通过所有 3 个参数显示出更多的细胞，而缺血再灌注导致损伤侧比对侧肾脏有更高水平的 FMC 参与。生物发光显示，FMCs 开启了 I 型胶原的转录，涉及间充质谱系细胞。损伤后，Y 探针原位杂交主要发现于肾小管上皮网络中。最后，我们将 FMCs 与骨髓细胞进行了比较，发现它们具有相似的动力学，但在肾脏内的分布不同。我们得出结论，FMCs（1）是妊娠的长期后果，（2）是由于损伤或适应而被招募到肾脏，在那里它们激活了基质蛋白的转录机制。
