CELLULAR PERSISTENCE BEYOND BOUNDARIES: A COMPREHENSIVE REVIEW OF HUMAN MICROCHIMERISM, ITS BIOLOGICAL FOUNDATIONS, AND CLINICAL IMPLICATIONS
DOI:
https://doi.org/10.5281/zenodo.20229543Keywords:
microchimerism; fetomaternal cell trafficking; pregnancy; immune tolerance; autoimmune disease; stem cells; chimerism detection.Abstract
Microchimerism refers to the sustained coexistence of a genetically distinct, numerically minor cell population within a host organism. Although the phenomenon has been recognised for several decades, its biological significance remained underappreciated until advances in molecular detection made it possible to track rare cell lineages with high sensitivity and specificity. The present review synthesises current knowledge regarding the origin, trafficking, and long-term fate of microchimeric cells in humans, with particular emphasis on fetomaternal exchange during pregnancy, the role of stem-cell-like progenitors in sustaining engraftment, and the dual — protective versus pathological — consequences that these foreign cells may exert on host tissues. Evidence drawn from epidemiological studies, in-vitro experiments, and animal models collectively suggests that microchimerism is not a passive residual phenomenon but rather an active participant in immune modulation, tissue homeostasis, and the pathogenesis of certain autoimmune conditions. Methodological considerations relevant to reliable detection are also addressed, alongside perspectives on therapeutic exploitation of microchimeric cell populations.
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References
1. Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci USA. 1996;93(2):705-708.
2. Nelson JL. The otherness of self: microchimerism in health and disease. Trends Immunol. 2012;33(8):421-427.
3. Lo YMD, Corbetta N, Chamberlain PF, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485-487.
4. Gammill HS, Nelson JL. Naturally acquired microchimerism. Int J Dev Biol. 2010;54(2-3):531-543.
5. Khosrotehrani K, Johnson KL, Cha DH, Salomon RN, Bianchi DW. Transfer of fetal cells with multilineage potential to maternal tissue. JAMA. 2004;292(1):75-80.
6. O'Donoghue K, Chan J, de la Fuente J, et al. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. Lancet. 2004;364(9429):179-182.
7. Stevens AM. Maternal microchimerism in health and disease. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):509-522.
8. Jonsson AM, Uzunel M, Gotherstrom C, Karlsson H, Westgren M. Maternal microchimerism in human fetal tissues. Am J Obstet Gynecol. 2008;198(3):325.e1-325.e6.
9. Dawe GS, Tan XW, Bhakoo KK. Cell migration from baby to mother. Cell Adhes Migr. 2007;1(1):19-27.
10. Rinkevich B. Quo vadis chimerism? Chimerism. 2011;2(1):1-5.
11. Reed AM, Picornell YJ, Harwood A, Kredich DW. Chimerism in children with juvenile dermatomyositis. Lancet. 2000;356(9248):2156-2157.
12. Nelson JL, Gillespie KM, Lambert NC, et al. Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet beta cell microchimerism. Proc Natl Acad Sci USA. 2007;104(5):1637-1642.
13. Ando T, Imaizumi M, Graves PN, Unger P, Davies TF. Intrathyroidal fetal microchimerism in Graves' disease. J Clin Endocrinol Metab. 2002;87(7):3315-3320.
14. Lambert NC, Lo YM, Erickson TD, et al. Male microchimerism in healthy women and women with scleroderma: cells or circulating DNA? A quantitative answer. Blood. 2002;100(8):2845-2851.
15. Artlett CM, Smith JB, Jimenez SA. Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med. 1998;338(17):1186-1191.
16. Burlingham WJ, Grailer AP, Heisey DM, et al. The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors. N Engl J Med. 1998;339(23):1657-1664.
17. van Rood JJ, Loberiza FR Jr, Zhang MJ, et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood. 2002;99(5):1572-1577.
18. Fujiki Y, Johnson KL, Tighiouart H, Peter I, Bianchi DW. Fetomaternal trafficking in the setting of maternal kidney disease. Kidney Int. 2008;74(5):689-695.
19. Guettier C, Sebagh M, Buard J, et al. Male cell microchimerism in normal and diseased female livers from fetal life to adulthood. Hepatology. 2005;42(1):35-43.
20. Tanaka A, Lindor K, Gish R, et al. Fetal microchimerism alone does not contribute to the induction of primary biliary cirrhosis. Hepatology. 1999;30(4):833-838.
21. Johnson KL, McAlindon TE, Mulcahy E, Bianchi DW. Microchimerism in a female patient with systemic lupus erythematosus. Arthritis Rheum. 2001;44(9):2107-2111.
22. Kamper-Jorgensen M, Biggar RJ, Tjonneland A, et al. Opposite effects of microchimerism on breast and colon cancer. Eur J Cancer. 2012;48(14):2227-2235.
23. Boddy AM, Fortunato A, Wilson Sayres M, Aktipis A. Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb. Bioessays. 2015;37(10):1106-1118.
24. Srivatsa B, Srivatsa S, Johnson KL, Samura O, Lee SL, Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet. 2001;358(9298):2034-2038.
25. Castilla JA, Gil T, Molina J, Tovar V, Morell M, Herruzo A. Fetal cell microchimerism: is it a pregnancy-induced phenomenon or does it predate pregnancy? Hum Reprod. 2001;16(7):1534-1538.
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