Modulation of stem and progenitor cell differentiation, assays, and uses thereof

Patent Number: 7,498,171

One of the areas in which regenerative medicine is heading is the use of "drugs" to modulate the stem cell compartment.  For example, we have previously seen companies like Stem Cell Therapeutics performing clinical trials with EPO and hCG for stroke.  Drugs already in the clinic such as Velcade, have also been reported to affect the stem cell compartment. 

The current patent covers the use of various thalidomide analogues for preferentially stimulating hematopoietic stem cell (CD34 and CD133) differentiation along the myeloid pathway but not the erythroid pathway.  Interestingly the claims cover both in vitro and in vivo manipulation. 

In the first independent claim the patent covers "A method for promoting the differentiation of mammalian CD34+ or CD133+ hematopoietic stem cells to CFU-GM (colony-forming units-granulocyte/macrophage) while inhibiting their differentiation to BFU-E (blast-forming units-erythrocyte), said method comprising: contacting said stem cells with an amino-substituted thalidomide analog under conditions under which said stem cells differentiate, wherein the amino-substituted thalidomide analog is selected from the group consisting of 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione and 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, and wherein said contacting detectably increases the number of CFU-GM and detectably decreases the number of BFU-E differentiated from said stem cells relative to the numbers of CFU-GM and BFU-E differentiated from mammalian CD34+ or CD133+ hematopoietic stem cells not contacted with said amino-substituted thalidomide analog. "

Various thalidomide analogues have been previously reported by Kyle Chan's group from Celgene to manipulate the hematopoietic compartment, for example in this JCI paper, thalidomide analogues pomalidomide and lenalidomide were found to synergize with hydroxyurea for stimulation of fetal hemoglobin production. 

It will be interesting to see if these compounds affect other stem cell compartments as well, such as endogenous cardiac or neural stem cells.

View this patent on the USPTO website.