Selecting Potent Immune Suppressive Mesenchymal Stem Cells
Paris, France -
It is widely known that mesenchymal stem cells, whether derived from the bone marrow, cord blood, or menstrual blood all possess some degree of immune suppressive activity. This is one of the reasons why mesenchymal stem cells are being used in clinical trials in a "universal donor" manner, and why the first marketing approval more than likely will be the BLA for Osiris using mesenchymal stem cells to treat the inflammatory condition graft versus host disease.
An important question is what if more potent immune suppressive mesenchymal stem cells can be collected from a population of mesenchymal stem cells by selecting for a specific surface marker? For example, selection of adipose derived mesenchymal stem cells for CD9 is associated with increased angiogenic activity.
In a recent paper (Nasef et al. Selected Stro-1-enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation. Int J Lab Hematol 2009 Feb;31(1):9- 19) selection of mesenchymal stem cells with increased immune suppressive activity was performed based on sorting of cells for higher expression of the molecule STRO-1.
The authors purified bone marrow derived mesenchymal stem cells into Stro-1 high expressing cells and Stro-1 low expressing cells and found that Stro-1 expression was associated with:
1. Increased suppressive activity on ongoing mixed lymphocyte reaction.
2. Increased suppression of T cell proliferation in a contact dependent manner.
3. Upregulated expression of IL-8, LIF, IDO, HLA-G, and VCAM1.
4. Expression of TGF-beta and IL-10 was induced only after contact with T cells.
These data suggest two things: firstly it may be beneficial to select for subsets within subsets of mesenchymal stem cells when trying to treat a specific condition; and secondly, when doing in vitro experiments looking at gene products made by mesenchymal stem cells, it is important to culture the mesenchymal stem cells with other cells, since the mesenchymal stem cell in its basal state may not be producing cytokines you are looking for.