Microchimeric Fetal Cells Are Recruited to Maternal Kidney following Injury and Activate Collagen Type I Transcription

Abstract

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.

The Genetic Basis of Graves Disease

“…Although these cells could theoretically contribute to postpartum exacerbation of thyroid inflammation [251,258,259] these data are compatible with high prevalence of fMC in human AITD being a consequence rather than the cause of disease. Indeed, the hypothesis that presence of fetal cells was associated with the maternal response to injury (inflammatory or other) as opposed to causing disease was proposed relatively early [260] and is consistent with observations in animal models [261-263] and humans [264]. …”

Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury

“…The identification 4 of male FMC bearing epithelial, leukocyte, or hepatocyte markers in various tissue specimens from women with male offspring initiated the concept that fetal cells might have stem cell capabilities with multilineage potential. This was further supported by a range of studies demonstrating FMC plasticity along different lineages such as lymphoid 5,6 mesenchymal, [7][8][9] endothelial, [10][11][12] neuronal, 13 epithelial, and hepatic. 14,15 This broad differentiation capacity raises the question of the origin of FMC transferred to the mother during pregnancy.…”

Unravelling the biological secrets of microchimerism by single-cell analysis

“…Thus, termination of pregnancy or miscarriage enables direct transfer of the cells [ 38 , 99–101 ]. Differentiated microchimeric cells were found to be derived from the mesodermal [ 94 ], ectodermal [ 41 , 79 , 102 ] and endodermal [ 91 , 103 , 104 ] lineage. Although all these cells originate from the epiblast, it cannot be ruled out that microchimerism establishes from placental cells.…”

“…This is of special interest for some samples containing a relatively high rate of microchimeric cells (e.g. in organ injury models, [ 79 , 81–83 , 95 , 104 ]). This way, the problem of cell loss of microchimeric cells or other subpopulations because of the use of inappropriate or unknown markers will be kept at a minimum.…”