Skip to main content
SpringerLink
Log in
Book cover

Human Fetal Tissue Transplantation pp 15–23Cite as

Fetomaternal Cell Trafficking: A Window into the Long-Term Health Effects of Treating Disease with Fetal Cell/Tissue Transplants?

  • Chapter
  • First Online:

  • 877 Accesses

Abstract

During pregnancy, fetal hematopoietic cells carrying paternal human leukocyte antigens (HLA) migrate into maternal circulation, and vice versa, maternal nucleated cells can be detected in fetal organs and umbilical cord blood, indicating the presence of bidirectional cell traffic between mother and fetus. The result is that both mother and infant exhibit microchimerism (Mc); that is, both have small numbers of cells and cell-free DNA that come from two genetically distinct individuals. Evidence is mounting that this is not a rare phenomenon, but that it occurs commonly in humans and other placental species, and that the chimeric cells may persist indefinitely in many individuals with no evidence of an immune attack against those cells. In this chapter, we briefly review maternal–fetal immune tolerance and explore what is known about the effects of fetomaternal (FMc) and maternal–fetal microchimerism (MFc) on the biology of both individuals in health and in illness. Perhaps better knowledge of these effects of microchimerism will instruct as to how long-term allogeneic coexistence within an organism can impact chronic disease, cancer biology, regenerative medicine, and fetal–maternal immunology.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Schmori CG. Pathologish-anatomische Uunter­suchungen uber Puerperal-Eklampsia. Leipzig: Verlag FCW Vogel; 1983.

    Google Scholar 

  2. Gammill HS, Nelson JL. Naturally acquired microchimerism. Int J Dev Biol. 2010;54(2–1):531–43.

    Article  PubMed  Google Scholar 

  3. Taylor JF. Sensitization of Rh-negative daughters by their Rh-positive mothers. N Engl J Med. 1967;276:547–51.

    Article  PubMed  CAS  Google Scholar 

  4. Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, Demaria M. Male progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci USA. 1996;93:705–8.

    Article  PubMed  CAS  Google Scholar 

  5. Lo Y, Tien M, Lau T, Haines C, Leung T, Poon P, Wainscoat J, Johnson P, Chang A, Hjelm N. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet. 1998;62:768–75.

    Article  PubMed  CAS  Google Scholar 

  6. Geifman-Holzman O, Grotegut CA, Gaughan JP. Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood-a meta-analysis. Am J Obstet Gynecol. 2006;195:1163–73.

    Article  Google Scholar 

  7. Hahn S, Lapaire O, Tercanli S, Kolla V, Hosli I. Determination of fetal chromosome aberrations from fetal DNA in maternal blood: has the challenge finally been met? Expert Rev Mol Med. 2011;13:16.

    Article  Google Scholar 

  8. Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB J. 2005;19:681–93.

    Article  PubMed  CAS  Google Scholar 

  9. Fournel S, Aguerre-Girr M, Huc X, et al. Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol. 2000;164:6100–4.

    PubMed  CAS  Google Scholar 

  10. Mor G, Gutierrez LS, Eliza M, Kahyaoglu F, Arici A. Fas ligand system-induced apoptosis in human placenta and gestational trophoblastic disease. Am J Reprod Immunol. 1998;40:89–94.

    Article  PubMed  CAS  Google Scholar 

  11. Hunt JS, Vassmer D, Ferguson TA, Miller L. Fas ligand is positioned in mouse uterus and placenta to prevent trafficking of activated leukocytes between the mother and the conceptus. J Immunol. 1997;158:4122–8.

    PubMed  CAS  Google Scholar 

  12. Munn DH, Zhou M, Attwood JT, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281:1191–3.

    Article  PubMed  CAS  Google Scholar 

  13. Von Rango U, Krusche CA, Beier HM, Classen-Linke I. Indoleamine- dioxygenase is expressed in human decidua at the time maternal tolerance is established. J Reprod Immunol. 2007;74:34–45.

    Article  Google Scholar 

  14. Miwa T, Zhou L, Hilliard B, Molina H, Song WC. Crry, but not CD59 and DAF, is indispensable for murine erythrocyte protection in vivo from spontaneous complement attack. Blood. 2002;99:3707–16.

    Article  PubMed  CAS  Google Scholar 

  15. Magatti M, De Munari S, Vertua E, Gibelli L, Wengler GS, Parolini O. Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells. 2008;26:182–92.

    Article  PubMed  CAS  Google Scholar 

  16. Parolini O, Soncini M. Placenta as a source of stem cells and as a key organ for fetomaternal tolerance. Bhattacharya N, Stubblefield P, editors. Regenera­tive medicine using pregnancy-specific biological substances, 11. doi:10.1007/978-1-84882-718-9_2. © Springer-Verlag London Limited; 2011.

  17. Ichinohe T. Long-term feto-maternal microchimerism revisited: microchimerism and tolerance in hematopoietic stem cell transplantation. Chimerism. 2010;1(1):39–43.

    Article  PubMed  Google Scholar 

  18. Cavell B. Transplacental metastasis of malignant melanoma. Report of a case. Acta Paediatr Suppl. 1963;146:37–40.

    Article  Google Scholar 

  19. Brodsky I, Baren M, Kahn SB, et al. Metastatic malignant melanoma from mother to fetus. Cancer. 1965;18:1048–54.

    Article  PubMed  CAS  Google Scholar 

  20. Jackisch C, Louwen F, Schwenkhagen A, et al. Lung cancer during pregnancy involving the products of conception and a review of the literature. Arch Gynecol Obstet. 2002;268:69–77.

    PubMed  Google Scholar 

  21. Astigiano S, Damonte P, Fossati S, et al. Fate of embryonal carcinoma cells injected into postimplantation mouse embryos. Differentiation. 2005;73:484–90.

    Article  PubMed  CAS  Google Scholar 

  22. Altshuler G. Toxoplasmosis as a cause of hydranencaphaly. Am J Dis Child. 1973;127:427–9.

    Google Scholar 

  23. Bittencourt AL. Congenital chagas disease. Am J Dis Child. 1976;130:97–103.

    PubMed  CAS  Google Scholar 

  24. Bierman HR, Kelly K, Cordes F, et al. The influence of histamine upon the circulating leukocyte level in patients with the leukemias. Blood. 1956;11:709–19.

    PubMed  CAS  Google Scholar 

  25. Schröder J. Transplacental passage of blood cells. J MedGenet. 1975;12:230–42.

    Google Scholar 

  26. Chen CP, Lee MY, Huang JP, et al. Trafficking of multipotent mesenchymal stromal cells from maternal circulation through the placenta involves vascular endothelial growth factor receptor-1 and integrins. Stem Cells. 2008;26:550–61.

    Article  PubMed  CAS  Google Scholar 

  27. Lo YM, Lo ES, Watson N, et al. Two-way cell traffic between mother and fetus: biologic and clinical implications. Blood. 1996;88:4390–5.

    PubMed  CAS  Google Scholar 

  28. Lo YM, Lau TK, Chan LY, et al. Quantitative analysis of the bidirectional fetomaternal transfer of nucleated cells and plasma DNA. Clin Chem. 2000;46:1301–9.

    PubMed  CAS  Google Scholar 

  29. Bonney EA, Matzinger P. The maternal immune system’s interaction with circulating fetal cells. J Immunol. 1997;158:40–7.

    PubMed  CAS  Google Scholar 

  30. Kadowaki J, Thompson RI, Zuelzer WW. XX-XY lymphoid chimaerism in congenital immunological deficiency syndrome with thymic alymphoplasia. Lancet. 1965;2:1152–6.

    Article  PubMed  CAS  Google Scholar 

  31. Githens JH, Muschenheim F, Fulginiti VA, et al. Thymic alymphoplasia with XX-XY lymphoid chimerism secondary to probable maternofetal transfusion. J Pediatr. 1969;75:87–94.

    Article  PubMed  CAS  Google Scholar 

  32. Anderson CC, Matzinger P. Immunity or tolerance: opposite outcomes of microchimerism from skin grafts. Nat Med. 2001;7:80–7.

    Article  PubMed  CAS  Google Scholar 

  33. Maloney S, Smith A, Furst DE, et al. Microchimerism of maternal origin persists into adult life. J Clin Invest. 1999;104:41–7.

    Article  PubMed  CAS  Google Scholar 

  34. Wan W, Shimizu S, Ikawa H, et al. Maternal cell traffic bounds for immune modulation: tracking maternal H-2 alleles in spleens of baby mice by DNA fingerprinting. Immunology. 2002;107:261–7.

    Article  PubMed  CAS  Google Scholar 

  35. Claas FH, Gijbels Y, van der Velden-de MJ, et al. Induction of B cell unresponsiveness to noninherited maternal HLA antigens during fetal life. Science. 1988;241:1815–7.

    Article  PubMed  CAS  Google Scholar 

  36. Nelson GW, Martin MP, Gladman D, et al. Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis. J Immunol. 2004;173:4273–6.

    PubMed  CAS  Google Scholar 

  37. Kaplan J, Land S. Influence of maternofetal histocompatibility and MHC zygosity on maternal ­microchimerism. J Immunol. 2005;174:7123–8.

    PubMed  CAS  Google Scholar 

  38. Ichinohe T, Maruya E, Saji H. Long-term feto-­maternal microchimerism: nature’s hidden clue for alternative donor hematopoietic cell transplantation? Int J Hematol. 2002;76(3):229–37.

    Article  PubMed  Google Scholar 

  39. Rubinstein A, Goldstein H, Calvelli T, et al. Mater­nofetal transmission of human immunodeficiency virus-1: the role of antibodies to the V3 ­primary ­neutralizing domain. Pediatr Res. 1993;33:76–8.

    Article  Google Scholar 

  40. Bucher C, Stern M, Buser A, et al. Role of primacy of birth in HLA-identical sibling transplantation. Blood. 2007;110:468–9.

    Article  PubMed  CAS  Google Scholar 

  41. Adams KM, Holmberg LA, Leisenring W, Fefer A, Guthrie KA, Tylee TS, McDonald GB, Bensinger WI, Nelson JL. Risk factors for syngenic graft-versus-host disease after adult hematopoietic cell transplantation. Blood. 2004;104:1894–7.

    Article  PubMed  CAS  Google Scholar 

  42. Mahanty HD, Cherikh WS, Chang GJ, Baxter-Lowe LA, Roberts JP. Influence of pretransplant pregnancy on survival of renal allografts from living donors. Transplantation. 2001;72:228–32.

    Article  PubMed  CAS  Google Scholar 

  43. Holzgreve W, Hahn S, Zhong XY, et al. Genetic ­communication between fetus and mother: short- and long-term consequences. Am J Obstet Gynecol. 2007;196:372–81.

    Article  PubMed  Google Scholar 

  44. Artlett CM, Welsh KI, Black CM, et al. Fetomaternal HLA compatibility confers susceptibility to systemic sclerosis. Immunogenetics. 1997;47:17–22.

    Article  PubMed  CAS  Google Scholar 

  45. Lambert NC, Evans PC, Hashizumi TL, et al. Cutting edge: persistent fetal microchimerism in T ­lymphocytes is associated with HLA-DQA1*0501: implications in autoimmunity. J Immunol. 2000;164:5545–8.

    PubMed  CAS  Google Scholar 

  46. Nelson JL. Microchimerism and the pathogenesis of systemic sclerosis. Curr Opin Rheumatol. 1998;10:564–71.

    Article  PubMed  CAS  Google Scholar 

  47. Reed AM, Picornell YJ, Harwood A, et al. Chimerism in children with juvenile dermatomyositis. Lancet. 2000;356:2156–7.

    Article  PubMed  CAS  Google Scholar 

  48. Artlett CM, Ramos R, Jiminez SA, Childhood Myositis Heterogeneity Collaborative Group, et al. Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Lancet. 2000;356:2155–6.

    Article  PubMed  CAS  Google Scholar 

  49. Buyon JP. Neonatal lupus and autoantibodies reactive with SSA/Ro-SSB/La. Scand J Rheumatol Suppl. 1998;107:23–30.

    PubMed  CAS  Google Scholar 

  50. Schröder J, Schröder E, Cann HM. Fetal cells in the maternal blood. Lack of response of fetal cells in maternal blood to mitogens and mixed leukocyte culture. Hum Genet. 1977;38:91–7.

    Article  PubMed  Google Scholar 

  51. Troeger C, Lapaire O, Zhong XY, Holzgreve, W. Implications of feto-maternal cell transfer in normal pregnancy. Bhattacharya N, Stubblefield P, editors. Regenerative medicine using pregnancy-specific ­biological substances, 11. doi:10.1007/978-1-84882-718-9_2. © Springer-Verlag London Limited; 2011.

  52. Yan Z, Lambert NC, Οstensen M, Adams KM, Guthrie KA, Nelson JL. Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis. Arthritis Rheum. 2006;54:2069–73.

    Article  PubMed  CAS  Google Scholar 

  53. Zeng XX, Tan KH, Yeo A, Sasajala P, Tan X, Xiao ZC, Dawe G, Udolph G. Pregnancy-associated progenitor cells differentiate and mature into neurons in the maternal brain. Stem Cells Dev. 2010;12:1819–30.

    Article  Google Scholar 

  54. Bhattacharya N. A study and follow-up (1999–2009) of human fetal neuronal tissue transplants at a heterotopic site outside the brain in case of advanced ­idiopathic parkinsonism. Bhattacharya N, Stubblefield P, editors. Regenerative medicine using pregnancy-specific biological substances, 407. doi:10.1007/978-1-84882-718-9_39. © Springer-Verlag London Limited; 2011.

  55. Miller RK. Fetal drug therapy: principles and issues. Clin Obstet Gynaecol. 1991;34(2):241–50.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Regenerative Medicine and Translational Science, Calcutta School of Tropical Medicine, Calcutta, West Bengal, India

    Niranjan Bhattacharya D.Sc., M.D., M.S., FACS (USA)

  2. Department of Ob/Gyn, Boston University, Boston, MA, USA

    Phillip Stubblefield M.D.

Authors
  1. Niranjan Bhattacharya D.Sc., M.D., M.S., FACS (USA)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Phillip Stubblefield M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Niranjan Bhattacharya D.Sc., M.D., M.S., FACS (USA) .

Editor information

Editors and Affiliations

  1. Southend Park 55, Kolkata, 700029, India

    Niranjan Bhattacharya

  2. Dept. Obstetrics & Gynaecology, Boston University Medical Centre, E. Concord Street 85, Boston, 02118, Massachusetts, USA

    Phillip Stubblefield

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Bhattacharya, N., Stubblefield, P. (2013). Fetomaternal Cell Trafficking: A Window into the Long-Term Health Effects of Treating Disease with Fetal Cell/Tissue Transplants?. In: Bhattacharya, N., Stubblefield, P. (eds) Human Fetal Tissue Transplantation. Springer, London. https://doi.org/10.1007/978-1-4471-4171-6_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4171-6_2

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4170-9

  • Online ISBN: 978-1-4471-4171-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation