Abstract

The placenta is a readily available and ethically non-controversial source of large amounts of therapeutic stem cells. We isolated adherent cells from the Umbilical Cord (UC) and the Amnion Chorion (AC) of term placentas. These Placenta Derived Adherent Cells (PDACs) displayed a cell surface phenotype of CD29+, CD44+, CD73+, CD90+, CD105+, CD200+, CD34, and constitutively secreted IL-6, IL-8 and Monocyte Chemoattractant protein-1 (MCP-1). PDACs demonstrated in vitro pluripotency and suppressed T cell proliferation in both the allogeneic mixed leukocyte reaction, and the autologous EBV regression assay. Because progenitor cells have been described to inhibit tumor growth in some systems, the role of PDACs in tumor suppression was investigated.

EBV transformed tumor cells were cultured either alone, or with AC or UC PDACs. After 6 days, live (7-AAD Annexin-V) tumor cells were counted on a flow cytometer. Free growing tumor cells numbered 40,000. When tumor cells were co-cultured with AC or UC PDACs, the growth was suppressed to 10,000 cells, a suppression of 75%. We designed and tested a panel of tumor cell lines that included retinoblastoma (RB), histiocytic lymphoma (HL), chronic myelogenous leukemia (CML), and colon adenocarcinoma (CAC). The tissue origin of the selected tumor cell lines included neuronal tissue (retinoblastoma), epithelium (carcinomas) and the hematopoietic lineage (lymphomas and CML). Co-culture experiments showed that the growth of all tumor lines was suppressed more than 40%. When a transwell was introduced separating PDACs and tumor cells, contact dependency of suppression was 12% for HL, 22% for CML, 42% for CAC, and 51% for EBV transformed tumor cells.

These results indicate that PDACs may have therapeutic value with respect to certain cancers.

Disclosures: Casper Paludan, Jia-Lun Wang, Qian Ye, James Edinger, Wolfgang Hofgartner, Robert Hariri are all employed by Celgene Corporation or its affiliates or subsidiaries.; All Celgene Corporation authors have stock options.; There is an agreement in place between Celgene Corporation and PHRI.; Gilla Kaplan sits on the Board of Directors for Celgene Corporation.

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