Introduction: We have recently reported that immature myeloid cells (IMCs), first reported to infiltrate malignant tumors, are present in mouse placentas and similarly promote angiogenesis.
We sought to determine whether these proangiogenic cells are present also in human placentas and whether they express similar genes as in tumors.

Materials and Methods: Human placental biopsies were analyzed for the presence and location of CD45+CD33+LIN2-HLADR- IMCs using flow cytometry (FACS) and confocal microscopy.
The ability of IMCs to promote angiogenesis was determined by human umbilical vein endothelial cell (HUVEC) tube formation assays. Global gene expression patterns of mouse placental- or tumor CD11b+Gr1+ IMCs were analyzed using Affymetrix microarrays and their similarity was determined using the mass-distance measure algorithm. Real time quantitative PCR (qPCR) was used to validate microarray data.

Results : Data from human term- and discordant twin placentas indicate that IMCs comprise up to 40% of hematopoietic cells, in close proximity to blood vessels, and in correlation with placental weight. FACS-sorted human placental IMCs are proangiogenic as they enhanced tube formation of HUVEC cells in vitro. Genome-wide expression data indicated that IMCs derived from placentas and tumors share similar gene clusters of proangiogenic factors, inflammatory cytokines, chemokines and their receptors.

Conclusion: Human placentas are populated by IMCs, and their presence corrleates with placental mass. Placental IMCs resemble tumor IMCs both by their proangiogenic properties and
by expressing similar genes. The notion that placentas utilize a similar proangiogenic machinery as malignant tumors is intriguing and its relevance to human placental pathologies is the subject of our current investigation.

Authors

Ofer Fainarua, Shay Hantisteanua, Elad Mei-Dana, Golan Yonab, Adrian Ellenbogena and Mordechai Hallaka

Laboratory for Reproductive Immunology and IVF Unit, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Faculty of Medicine, Technion – Israel Institute
of Technology; bDepartment of Structural Biology, Stanford University, Palo Alto, CA, USA.