The Rule of Mesenchymal Stem Cells in Marrow Transplantation
The founding principles of hematopoietic cell transplantation are that infused hematopoietic stem cells home and engraft in the marrow microenvironment and expand and proliferate to reconstitute all of the blood lineages. Yet it may be that another cellular component of the marrow microenvironment, namely the mesenchymal stem cell, has the potential to synergize with current hematopoietic cell transplantation regimens and positively impact the field of hematopoietic cell transplantation. Clinical trials with mesenchymal stem cells are ongoing. Owen was the first to propose that non-hematopoietic mesenchymal stem cells with fibroblastic, osteogenic, and adipocytic potential reside in the marrow microenvironment.
What is the Mesenchymal Stem Cells?
At present, mesenchymal stem cells are considered a heterogeneous population of cells because no specific marker or combination of markers is accepted to uniquely define these cells, although surface expression of the three antigens, CD105, CD73, and CD90 (Thy1), appear important.
Similarly, there is no single functional assay to distinguish mesenchymal stem cells, analogous to the repopulation assay for hematopoietic stem cells. The lack of a consensus on features to characterize these cells makes it difficult to compare and contrast study outcomes, and this slows the progress of the field. Nonetheless, mesenchymal stem cells are recognized to have diverse biologic properties, suggesting remarkable potential as cellular therapy. In particular, the cytokine-generating and immunomodulatory properties of mesenchymal stem cells hold promise for clinical applications inhematopoietic cell transplantation.
The source of Mesenchymal Stem Cells
Mesenchymal Stem Cells are most commonly isolated from marrow but can be obtained from placenta, umbilical cord blood, adipose tissue, and fetal lung and blood. The current opinion is that mesenchymal stem cells do not circulate in cytokine-mobilized blood. For isolation from the marrow, mononuclear cells are placed in tissue culture and the mesenchymal stem cells adhere to the plastic surface of the tissue culture vessels while the non-adherent cells are easily removed by changing the culture media. Once isolated, mesenchymal stem cells are expanded in vitro prior to preparation for a clinical trial; this extensive cell replication raises theoretical concern about malignant transformation. However, malignant transformation of MSCs after infusion into human subjects in a clinical trial has not been reported.