No abstract

Broad differentiation capacity has been described for mesenchymal stem cells (MSC) from human bone marrow. We sought to identify genes associated with the immature state and pluripotency of this cell type. To prove the pluripotent state of the MSC, differentiation into osteocytes, adipocytes, and chondrocytes was performed in vitro. In contrast, normal skin cells did not harbor these differentiation abilities. We compared the expression profile of human bone marrow MSC with cDNA from one primary human skin cell line as control, using a cDNA chip providing 9600 genes. The identity of all relevant genes was confirmed by direct sequencing. Data of gene array expression were corroborated employing quantitative PCR analysis. About 80 genes were differently expressed more than threefold in MSC compared to mature skin fibroblasts. Interestingly, primary human MSC were found to upregulate a number of genes important for embryogenesis such as distal-less homeo box 5, Eyes absent homolog 2, inhibitor of DNA binding 3, and LIM protein. In contrast, mesenchymal lineage genes were downregulated in MSC in comparison to skin cells. We also detected expression of some genes involved in neural development, indicating the broad differentiation capabilities of MSC. We conclude that human mesenchymal stem cells harbor an expression profile distinct from mature skin fibroblast, and genes associated with developmental processes and stem cell function are highly expressed in adult mesenchymal stem cells.

Mesenchymal stem cells (MSC) obtained from human bone marrow have been described as adult stem cells with the ability of extensive self-renewal and clonal expansion, as well as the capacity to differentiate into various tissue types and to modulate the immune system. Some data indicate that leukapheresis products may also contain non-hematopoietic stem cells, as they occur in whole bone marrow transplantation (BMT). However, there is still controversy whether MSC expand in the host after transplantation like blood progenitor cells do. Therefore, we were interested in finding out if graft MSC can be detected in leukapheresis products and in bone marrow after BMT and peripheral blood stem cell transplantation (PBSCT). Every sample from total bone marrow transplants exhibited growth of MSC after in vitro culture, but not one of nine leukapheresis products did. In addition, bone marrow aspirates of 9 patients receiving BMT and of 18 patients after PBSCT were examined for origin of MSC. Almost all MSC samples exhibited a complete host profile, whereas peripheral blood cells were of donor origin. We conclude that even if trace amounts of MSC are co-transplanted during PBSCT or BMT, they do not expand significantly in the host bone marrow.