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Fetal microchimerism as an explanation of disease

Nature Reviews Endocrinology volume 7, pages 89–97 (2011)Cite this article

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Abstract

Fetal cell microchimerism is defined as the persistence of fetal cells in the mother after birth without any apparent rejection. Fetal microchimeric cells (FMCs) engraft into the maternal bone marrow for decades after delivery and are able to migrate to blood and tissues. This phenomenon was hypothesized to have a detrimental role in autoimmune diseases, but data are still controversial and debated. In malignant tumors, fetal cell microchimerism has been postulated to have a positive effect on tumor burden, although some evidence suggests that FMCs may be involved in neoplastic progression. At the peripheral level, circulating FMCs are less frequently detected in patients with thyroid cancer, breast cancer or other solid, hematologic malignancies than in healthy individuals, which suggests a protective role for fetal cell microchimerism. In tissues, FMCs have been found in tumor sections from malignancies such as thyroid, breast, cervix, lung cancers and melanomas and have been shown to differentiate into epithelial, hematopoietic, endothelial and mesenchymal cells. FMCs with hematopoietic differentiation have been postulated to have a role in destroying the tumor, whereas mesenchymal and epithelial cells could participate in repair processes. Endothelial cells, on the other hand, are believed to play a part in tumor progression. This Review provides an overview of the role of fetal cell microchimerism in autoimmune and benign or malignant nonautoimmune diseases. Moreover, the mechanisms by which fetal cell microchimerism is believed to modulate the protection against cancer or tumor progression will be discussed, together with future research directions.

Key Points

  • Fetal microchimeric cells (FMCs) can engraft into maternal bone marrow and provide a renewing source of fetal cells in maternal blood for decades after delivery

  • Three hypotheses have been put forward concerning microchimerism and human health: a chronic inflammatory response that causes tissue damage; a protective role in repair of tissues; or a physiologic event without biological significance

  • In systemic and nonsystemic autoimmune diseases, a pathogenic role of fetal cell microchimerism remains controversial, as study results comparing the number of FMCs in patients and healthy controls are conflicting

  • FMCs are more frequent in the blood of healthy women compared with patients with neoplasms, which indicates that FMCs have the potential to participate in immune surveillance

  • At the tissue level, FMCs are preferentially located in tumoral tissues rather than nontumoral areas and are morphologically undistinguishable from the surrounding maternal cells

  • Some FMCs are CD45-positive, possibly for tumor destruction, whereas others can differentiate into epithelial or mesenchymal cells to regenerate tissue or endothelial cells to participate in vessel formation

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Figure 1: Methods to detect male fetal cells.
Figure 2: Schematic representation of the organs involved in autoimmune diseases (left) and in neoplastic processes (right) in which fetal cell microchimerism has been studied.
Figure 3: Possible roles of microchimeric male cells.
Figure 4: Immunophenotypic characterization of papillary thyroid cancer.

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Authors and Affiliations

  1. Endocrine Unit, Fondazione IRCCS Ca' Granda, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy

    Laura Fugazzola

  2. Department of Medical Sciences, Università degli Studi di Milano, Via Francesco Sforza 35, 20122, Milan, Italy

    Valentina Cirello & Paolo Beck-Peccoz

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  1. Laura Fugazzola
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L. Fugazzola and V. Cirello researched the data for the article. P. Beck-Peccoz provided a substantial contribution to discussions of the content. L. Fugazzola wrote the review. All authors reviewed and edited the manuscript before submission.

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Correspondence to Laura Fugazzola.

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Fugazzola, L., Cirello, V. & Beck-Peccoz, P. Fetal microchimerism as an explanation of disease. Nat Rev Endocrinol 7, 89–97 (2011). https://doi.org/10.1038/nrendo.2010.216

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