Engraftment potential of human placenta-derived mesenchymal stem cells after in utero transplantation in rats.
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.
Division of High Risk Pregnancy, Mackay Memorial Hospital, 92 Sec. 2 Chung-San North Road, Taipei 104, Taiwan. cpchen@ms2.mmh.org.tw
Chie-Pein
CP
Chen
Shu-Hsiang
SH
Liu
Jian-Pei
JP
Huang
John D
JD
Aplin
Yi-Hsin
YH
Wu
Pei-Chun
PC
Chen
Cing-Siang
CS
Hu
Chun-Chuan
CC
Ko
Ming-Yi
MY
Lee
Chia-Yu
CY
Chen
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D046528:Chimerism; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D005333:Fetus / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley