Differential Properties Of Stromal Cells From Bone Marrow, Adipose, Cardiac and Liver

Bone marrow (BM) stromal cells (also termed mesenchymal stem cells; MSC) have been extensively studied and shown to control differentiation of hematopoietic stem cells (HSCs) in part through secreted growth factors. In addition, MSCs support the growth of tumor cells both in vitro and in vivo. As MSCs are being evaluated in a number of clinical trials for regenerative medicine approaches, it is critical to understand the role of stromal cells in different tissues. Stromal cells were isolated from various human tissues including adipose (Ad), cardiac (Car) and liver (Liv) tissues as well as bone marrow (BM) and had an identical appearance in culture. We have compared the stromal cells from these tissues and demonstrate that although they have similar morphology and surface marker expression (CD105+/CD90+/CD73+ and CD45-/CD34-) they have differential biological properties. BM MSCs have been shown previously to support both normal hematopoietic cells and tumor cells.

To test the functional properties of the stromal cell lines we co-cultured stromal cells with either cord blood (CB) cells or tumor cells (K562). As we have previously reported, co-culture of CB on BM-MSCs resulted in expansion of hematopoietic cells. Similarly, Ad stromal cells supported expansion of hematopoietic cells, however, Liv and Car stromal cells failed to expand the CB cells. The effect of the Car stroma was through a cytostatic mechanism as removal of the CB cells from the stromal cells after 7 days of co-culture resulted in hematopoietic cell expansion and detection of colony forming cells by methycellulose assay. We also tested the potential of the stromal cells to support tumor cell growth by co-culturing K562 cells with the stromal cells. Ad and Liv stroma supported growth of the K562 cells similar to BM MSCs, while Car stromal cells inhibited K562 cell growth with few viable cells after 7 days of culture.

These data suggest that the function of stromal cells from different tissue is variable. In particular, tumor development in cardiac tissue is a rare event and our data suggest that Car stromal cells may play a key role in inhibiting proliferation of tumor cells. Further we propose that non homologous use of stromal cells in clinical applications may have deleterious effects, for example the use of BM-MSCs to repair ischemic tissue in the heart may lead to a tumor supportive environment in cardiac tissue.