Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture

Human mesenchymal stem cells (hMSC) have been isolated and characterized extensively for a variety of clinical applications. Yet it is unclear how the phenomenon of hMSC plasticity can be safely and reasonably exploited for therapeutic use.

We have generated mesenchymal stem cells (MSC) from normal human BM and identified a novel cell population with a transformed phenotype. This cell population was characterized by morphologic, immunophenotypic, cytogenetic analyzes and telomerase expression. Its tumorigenicity in NOD/SCID mice was also studied.

A subpopulation of cells in hMSC culture was noted to appear morphologically distinct from typical MSC. The cells were spherical, cuboidal to short spindle in shape, adherent and exhibited contact independent growth. Phenotypically the cells were CD133(+), CD34(-), CD45(-), CD90(low), CD105(-), VEGFR2(+). Cytogenetic analysis showed chromosome aneuploidy and translocations. These cells also showed a high level of telemerase activity compared with typical MSC. Upon transplantation into NOD/SCID mice, multiple macroscopic solid tumors formed in multiple organs or tissues. Histologically, these tumors were very poorly differentiated and showed aggressive growth with large areas of necrosis.

The possible explanations for the origin of this cell population are: (1) the cells represent a transformed population of MSC that developed in culture; (2) abnormal cells existed in the donor BM at rare frequency and subsequently expanded in culture. In either case, the MSC culture may provide a suitable environment for transformed cells to expand or propagate in vitro. In summary, our data demonstrate the potential of transformed cells in hMSC culture and highlight the need for karyotyping as a release criteria for clinical use of MSC.