HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2007-0406v1 2007-0406v2 26/2/550    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, C.-P. Articles by Yang, Y.-C. Search for Related Content PubMed PubMed Citation Articles by Chen, C.-P. Articles by Yang, Y.-C.

TRANSLATIONAL AND CLINICAL RESEARCH

Trafficking of Multipotent Mesenchymal Stromal Cells from Maternal Circulation Through the Placenta Involves Vascular Endothelial Growth Factor Receptor-1 and Integrins

^aDivision of High Risk Pregnancy and
^bDepartment of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;
^cMackay Medicine, Nursing and Management College, Taipei, Taiwan;
^dDivision of Human Development, Medical School, University of Manchester, Manchester, United Kingdom;
^eInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan;
^fBioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan

Key Words. Integrins • Multipotent mesenchymal stromal cell • Microchimerism • Placenta Vascular endothelial growth factor receptor

Correspondence: Correspondence: Chie-Pein Chen, M.D., Ph.D., Division of High Risk Pregnancy, Mackay Memorial Hospital, 92 Sec. 2 Chung San North Road, Taipei 104, Taiwan Telephone: 011-886-2-2543-3535; Fax: 011-886-2-2754-3769; e-mail: cpchen{at}ms2.mmh.org.tw

Received on May 24, 2007; accepted for publication on October 23, 2007.

First published online in STEM CELLS EXPRESS  November 1, 2007.


Maternal cells can become engrafted in various fetal organs during pregnancy. The nature of the cells and the mechanisms of maternofetal cell trafficking are not clear. We demonstrate that human lineage-negative, CD34-negative (Lin^–CD34^–) multipotent mesenchymal stromal cells express ₂, ₄, ₅, and β₁ integrins, which mediate their adhesion to endothelium, and vascular endothelial growth factor receptor-1 (VEGFR-1), which mediates their response to vascular endothelial growth factor A (VEGF-A). A maternal-fetal VEGF-A concentration gradient exists across the placental barrier, and cord blood plasma induces transendothelial and trans-Matrigel migration of stem cells in vitro. Migration is inhibited by a VEGF-A-neutralizing antibody or antibodies against VEGFR-1 or integrin ₂, ₄, ₅, or β₁. When Lin^–CD34^– multipotent mesenchymal stromal cells are transferred to rat maternal venous blood, they traffic through the placenta, engraft in various fetal organs, and persist in offspring for at least 12 weeks. Cell proliferation ability is retained in the xenogeneic placenta. Maternofetal trafficking is significantly reduced by blocking antibodies against integrins ₂, ₄, ₅, and β₁ or VEGFR-1. These results suggest that maternal microchimerism arises by the trafficking of multipotent mesenchymal stromal cells via VEGF-A- and integrin-dependent pathways across the hemochorial placenta to fetal tissues.

Disclosure of potential conflicts of interest is found at the end of this article.

This article has been cited by other articles:

				C.-P. Chen, S.-H. Liu, J.-P. Huang, J. D. Aplin, Y.-H. Wu, P.-C. Chen, C.-S. Hu, C.-C. Ko, M.-Y. Lee, and C.-Y. Chen Engraftment potential of human placenta-derived mesenchymal stem cells after in utero transplantation in rats Hum. Reprod., January 1, 2009; 24(1): 154 - 165. [Abstract] [Full Text] [PDF]