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Hum. Reprod. Advance Access published online on October 9, 2008
Human Reproduction, doi:10.1093/humrep/den356
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Engraftment potential of human placenta-derived mesenchymal stem cells after in utero transplantation in rats

Chie-Pein Chen1,2,3,5, Shu-Hsiang Liu2, Jian-Pei Huang1, John D. Aplin4, Yi-Hsin Wu2, Pei-Chun Chen2, Cing-Siang Hu2, Chun-Chuan Ko2, Ming-Yi Lee2 and Chia-Yu Chen2

1 Division of High Risk Pregnancy, Mackay Memorial Hospital, 92 Sec. 2 Chung-San North Road, Taipei 104, Taiwan 2 Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan 3 Mackay Medicine, Nursing and Management College, Taipei 112, Taiwan 4 Maternal and Fetal Health Research Group, University of Manchester, St Mary’s Hospital, Manchester M13 0JH, UK

5Correspondence address.Tel: +886-2-2543-3535; Fax: +886-2-2754-3769; E-mail: cpchen{at}ms2.mmh.org.tw

BACKGROUND: Human placental mesenchymal stem cells (hPMCs) are thought to be multipotent, but their fate after in utero transplantation is not known.

METHODS: hPMCs isolated from term placenta were assessed for their phenotype markers, mutilineage capacity, and immunomodulatory properties. Their engraftment potential was analyzed in a pregnant rat model after in utero transplantation at embryonic day 17. Immunohistochemistry, tracing of labeled cells, fluorescence in situ hybridization and real-time PCR were used to assess post-transplant chimerism.

RESULTS: In vitro, lineage-negative, CD34-negative hPMCs differentiated into osteocytes, adipocytes, hepatocytes and endothelial cells with tube formation, and actively suppressed the rat lymphocyte proliferative response to allogeneic lymphocyte stimulation (P < 0.0001). After in utero transplantation into pregnant rats, a low level of engraftment was achieved in various fetal tissues. Engraftment occurred in more than 60% of the fetal rats. Cells persisted for at least 12 weeks after delivery and evidence was obtained to suggest differentiation into specific lineages, including hepatocytes and hematopoietic cells. However, a greater number of hPMCs migrated to the placenta than to the fetus, thus limiting the degree of cell engraftment in fetal organs.

CONCLUSIONS: We conclude that hPMCs are mutipotent cells that can be engrafted long-term in immunocompetent rats after in utero transplantation.

Key words: engraftment/in utero transplantation/mesenchymal stem cells/placenta/rat

Submitted on August 14, 2007; resubmitted on August 17, 2008; accepted on August 21, 2008.


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