In utero cell transfer between porcine littermates
Andrea McConico A , Kim Butters B , Karen Lien B , Bruce Knudsen B , Xiaosheng Wu C , Jeffrey L. Platt D E and Brenda M. Ogle F G H
+ Author Affiliations
- Author Affiliations
A Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN 55901, USA.
B Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA.
C Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA.
D Department of Surgery, University of Michigan-Ann Arbor, Ann Arbor, MI 48109, USA.
E Department of Microbiology and Immunology, University of Michigan-Ann Arbor, Ann Arbor, MI 48109, USA.
F Material Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
G Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
H Corresponding author. Email: ogle@wisc.edu
Reproduction, Fertility and Development 23(2) 297-302 https://doi.org/10.1071/RD10165
Submitted: 25 March 2010 Accepted: 5 July 2010 Published: 4 January 2011
Abstract
Trafficking of cells between mother and fetus during the course of normal pregnancy is well documented. Similarly, cells are known to travel between twins that share either a placenta (i.e. monozygotic) or associated chorion (i.e. monochorionic). Transferred cells are thought to be channelled via the vessels of the placenta or vascular connections established via the chorion and the long-term presence of these cells (i.e. microchimerism) can have important consequences for immune system function and reparative capacity of the host. Whether cells can be transferred between twins with separate placentas and separate chorions (i.e. no vascular connections between placentas) has not been investigated nor have the biological consequences of such a transfer. In the present study, we tested the possibility of this type of cell transfer by injecting human cord blood-derived cells into a portion of the littermates of swine and probing for human cells in the blood and tissues of unmanipulated littermates. Human cells were detected in the blood of 78% of unmanipulated littermates. Human cells were also detected in various tissues of the unmanipulated littermates, including kidney (56%), spleen (33%), thymus (11%) and heart (22%). Human cells were maintained in the blood until the piglets were sacrificed (8 months after birth), suggesting the establishment of long-term microchimerism. Our findings show that the transfer of cells between fetuses with separate placentas and separate chorions is significant and thus such twins may be subject to the same consequences of microchimerism as monozygotic or monochorionic counterparts.
Additional keywords: cord blood, maternofetal transfer, microchimerism, stem cells, tolerance.
References
Amoroso, E. C. (1952). Placentation. In ‘Marshall’s Physiology of Reproduction’. 3rd edn. (Ed. A. S. Parkes.) pp. 127–311. (Longman: New York.)Anderson, D., Billingham, R. E., Lampkin, G. H., and Medawar, P. B. (1951). The use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle. Heredity 5, 379–397.
| The use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle.Crossref | GoogleScholarGoogle Scholar |
Billingham, R. E., Lampkin, G. H., Medawar, P. B., and Williams, H. L. L. (1952). Tolerance to homografts, twin diagnosis, and the freemartin condition in cattle. Heredity 6, 201–212.
| Tolerance to homografts, twin diagnosis, and the freemartin condition in cattle.Crossref | GoogleScholarGoogle Scholar |
BonDurant, R. H., McDonald, M. C., and Trommershausen-Bowling, A. (1980). Probable freemartinism in a goat. J. Am. Vet. Med. Assoc. 177, 1024–1025..
| 1:STN:280:DyaL3M7hs1yksA%3D%3D&md5=a2605c3dd669b536374c7ae84e9f4251CAS | 7193198PubMed |
Cirello, V., Recalcati, M. P., Muzza, M., Rossi, S., Perrino, M., Vicentini, L., Beck-Peccoz, P., Finelli, P., and Fugazzola, L. (2008). Fetal cell microchimerism in papillary thyroid cancer: a possible role in tumor damage and tissue repair. Cancer Res. 68, 8482–8488.
| Fetal cell microchimerism in papillary thyroid cancer: a possible role in tumor damage and tissue repair.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1CmsbrF&md5=d3b161d13f5df7223aa1cee6d87d39daCAS | 18922922PubMed |
Davies, M. L., Xu, S., Lyons-Weiler, J., Rosendorff, A., Webber, S. A., Wasil, L. R., Metes, D., and Rowe, D. T. (2010). Cellular factors associated with latency and spontaneous Epstein–Barr virus reactivation in B-lymphoblastoid cell lines. Virology 400, 53–67.
| Cellular factors associated with latency and spontaneous Epstein–Barr virus reactivation in B-lymphoblastoid cell lines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjtVCqtrk%3D&md5=67f45e02873edad675cce09760098774CAS | 20153012PubMed |
Forte, E., and Luftig, M. A. (2009). MDM2-dependent inhibition of p53 is required for Epstein–Barr virus B-cell growth transformation and infected-cell survival. J. Virol. 83, 2491–2499.
| MDM2-dependent inhibition of p53 is required for Epstein–Barr virus B-cell growth transformation and infected-cell survival.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXivF2rt7Y%3D&md5=ba4fecd561e468627a114ad43bfa21efCAS | 19144715PubMed |
Frandson, R. D. (1981). ‘Anatomy and Physiology of Farm Animals.’ 3rd edn. (Lea & Febiger: Philadelphia.)
Freedman, W. L., and Mc, M. F. (1960). Placental metastasis. Review of the literature and report of a case of metastatic melanoma. Obstet. Gynecol. 16, 550–560..
| 1:STN:280:DyaF3c%2FitFSrtQ%3D%3D&md5=91bfa6747b144d61966a728242991737CAS | 13701623PubMed |
Gadi, V. K., and Nelson, J. L. (2007). Fetal microchimerism in women with breast cancer. Cancer Res. 67, 9035–9038.
| Fetal microchimerism in women with breast cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFSnur7P&md5=64abe45a9c30e1b47c70f6fe4030d2f5CAS | 17909006PubMed |
Gadi, V. K., Malone, K. E., Guthrie, K. A., Porter, P. L., and Nelson, J. L. (2008). Case-control study of fetal microchimerism and breast cancer. PLoS One 3, e1706.
| Case-control study of fetal microchimerism and breast cancer.Crossref | GoogleScholarGoogle Scholar | 18320027PubMed |
Johansson, S., Dencker, L., and Dantzer, V. (2001). Immunohistochemical localization of retinoid binding proteins at the materno-fetal interface of the porcine epitheliochorial placenta. Biol. Reprod. 64, 60–68.
| Immunohistochemical localization of retinoid binding proteins at the materno-fetal interface of the porcine epitheliochorial placenta.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhtFCmsA%3D%3D&md5=92463a3b922dc11736ad48a95810cd9bCAS | 11133659PubMed |
Khosrotehrani, K., Reyes, R. R., Johnson, K. L., Freeman, R. B., Salomon, R. N., Peter, I., Stroh, H., Guegan, S., and Bianchi, D. W. (2007). Fetal cells participate over time in the response to specific types of murine maternal hepatic injury. Hum. Reprod. 22, 654–661.
| Fetal cells participate over time in the response to specific types of murine maternal hepatic injury.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2s7gs1Cnsw%3D%3D&md5=a5985394f2d33bf0072783a473fb9286CAS | 17074776PubMed |
Krohn, K., Ivemark, B. I., and Salo, K. (1970). A microangiographic study of the fetal arterial vasculature in the human placenta in uncomplicated pregnancy. Acta Obstet. Gynecol. Scand. 49, 205–214.
| A microangiographic study of the fetal arterial vasculature in the human placenta in uncomplicated pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE3M3jtlCktw%3D%3D&md5=400ddd11b786baebce426c7abca0eff6CAS | 5519492PubMed |
Lapaire, O., Holzgreve, W., Oosterwijk, J. C., Brinkhaus, R., and Bianchi, D. W. (2007). Georg Schmorl on trophoblasts in the maternal circulation. Placenta 28, 1–5.
| Georg Schmorl on trophoblasts in the maternal circulation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2s%2FlsFGktA%3D%3D&md5=4edd8c5c013919c362c42cfedbe58c39CAS | 16620961PubMed |
Leiser, R. (1985). Fetal vasculature of the human placenta: scanning electron microscopy of microvascular casts. Contrib. Gynecol. Obstet. 13, 27–31..
| 1:STN:280:DyaL2M3gt1ygsQ%3D%3D&md5=ad4fbb7ea40dd3f92c4bb5567a77951bCAS | 3995980PubMed |
Leiser, R., and Dantzer, V. (1988). Structural and functional aspects of porcine placental microvasculature. Anat. Embryol. 177, 409–419.
| Structural and functional aspects of porcine placental microvasculature.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1c3gsl2mtA%3D%3D&md5=31cba45e03e25202704384f28723e852CAS | 3364745PubMed |
Lillie, F. R. (1917). The free-martin, a study of the action of sex hormones in foetal life of cattle. J. Exp. Zool. 23, 371–452.
| The free-martin, a study of the action of sex hormones in foetal life of cattle.Crossref | GoogleScholarGoogle Scholar |
Loubière, L. S., Lambert, N. C., Flinn, L. J., Erickson, T. D., Yan, Z., Guthrie, K. A., Vickers, K. T., and Nelson, J. L. (2006). Maternal microchimerism in healthy adults in lymphocytes, monocyte/macrophages and NK cells. Lab. Invest. 86, 1185–1192..
| 16969370PubMed |
Ogle, B. M., Butters, K. A., Plummer, T. B., Ring, K. R., Knudsen, B. E., Litzow, M. R., Cascalho, M., and Platt, J. L. (2004). Spontaneous fusion of cells between species yields transdifferentiation and retroviral transfer in vivo. FASEB J. 18, 548–550..
| 1:CAS:528:DC%2BD2cXisVyhurs%3D&md5=99cf986854af9797536b15b54c2fc8c2CAS | 14715691PubMed |
Ogle, B. M., West, L. J., Driscoll, D. J., Strome, S. E., Razonable, R. R., Paya, C. V., Cascalho, M., and Platt, J. L. (2006). Effacing of the T cell compartment by cardiac transplantation in infancy. J. Immunol. 176, 1962–1967..
| 1:CAS:528:DC%2BD28XlsFyrsA%3D%3D&md5=8c53f6ea0ca2dc1e358a80d595279f67CAS | 16424228PubMed |
Ogle, B. M., Knudsen, B. E., Nishitai, R., Ogata, K., and Platt, J. L. (2009). Toward development and production of human T cells in swine for potential use in adoptive T cell immunotherapy. Tissue Eng. Part A 15, 1031–1040.
| Toward development and production of human T cells in swine for potential use in adoptive T cell immunotherapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlt1CktLY%3D&md5=3f76191f1e2ea617f151a324b50a12f7CAS | 18826341PubMed |
Østensen, M., Förger, F., Nelson, J. L., Schuhmacher, A., Hebisch, G., and Villiger, P. M. (2005). Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum. Ann. Rheum. Dis. 64, 839–844.
| Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum.Crossref | GoogleScholarGoogle Scholar | 15539410PubMed |
Padula, A. M. (2005). The freemartin syndrome: an update. Anim. Reprod. Sci. 87, 93–109.
| The freemartin syndrome: an update.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2M3ks1ChtQ%3D%3D&md5=78090189593d7bf5f4ef86dc57487d84CAS | 15885443PubMed |
Reynolds, A. G. (1955). Placental metastasis from malignant melanoma; report of a case. Obstet. Gynecol. 6, 205–209..
| 1:STN:280:DyaG2M7gslansQ%3D%3D&md5=eb9ad6a2d6377433cddabf9333a05848CAS | 13244979PubMed |
Rocklin, R. E., Kitzmiller, J. L., and Kaye, M. D. (1979). Immunobiology of the maternal–fetal relationship. Annu. Rev. Med. 30, 375–404.
| Immunobiology of the maternal–fetal relationship.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3M3otVGltg%3D%3D&md5=06adbcee4e1a05abe07e42d4a2aebfaeCAS |
Schroder, J., and De la Chapelle, A. (1972). Fetal lymphocytes in the maternal blood. Blood 39, 153–162..
| 1:STN:280:DyaE38%2FptlKrsA%3D%3D&md5=521c14f90fb9a5ea736489642d4a3b51CAS | 4109537PubMed |
Smith, K. C. P., Parkinson, T. J., Long, S. E., and Barr, F. J. (2000). Anatomical, cytogenetic and behavioural studies of freemartin ewes. Vet. Rec. 146, 574–578..
| 1:STN:280:DC%2BD3cvpvVKiug%3D%3D&md5=f4cc05455e4ffc0335ed85164728f7d4CAS | 10839234PubMed |
Srivatsa, B., Srivatsa, S., Johnson, K. L., Samura, O., Lee, S. L., and Bianchi, D. W. (2001). Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet 358, 2034–2038.
| Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38%2FktlersQ%3D%3D&md5=eebf43f8c129e1f7c3435fa82ba44c7cCAS | 11755610PubMed |
Tokita, K., Terasaki, P., Maruya, E., and Saji, H. (2001). Tumour regression following stem cell infusion from daughter to microchimeric mother. Lancet 358, 2047–2048.
| Tumour regression following stem cell infusion from daughter to microchimeric mother.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38%2FktlertQ%3D%3D&md5=091dce1d9c4009d5c814c8b86ebc5d76CAS | 11755614PubMed |
Walknowska, J., Conte, F. A., and Grumbach, M. M. (1969). Practical and theoretical implications of fetal–maternal lymphocyte transfer. Lancet 293, 1119–1122.
| Practical and theoretical implications of fetal–maternal lymphocyte transfer.Crossref | GoogleScholarGoogle Scholar |
Wang, Y., Iwatani, H., Ito, T., Horimoto, N., Yamato, M., Matsui, I., Imai, E., and Hori, M. (2004). Fetal cells in mother rats contribute to the remodeling of liver and kidney after injury. Biochem. Biophys. Res. Commun. 325, 961–967.
| Fetal cells in mother rats contribute to the remodeling of liver and kidney after injury.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXpslKnt74%3D&md5=6bcd7b38387cb30deac6a74472e9cefdCAS | 15541383PubMed |
Yan, Z., Lambert, N. C., Ostensen, M., Adams, K. M., Guthrie, K. A., and Nelson, J. L. (2006). Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis. Arthritis Rheum. 54, 2069–2073.
| Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XnslKhtbs%3D&md5=d7e4fb61419e09a11262f47883d9f57bCAS | 16804866PubMed |
