Selecting for better mesenchymal stem cells

New Orleans, LA - 

Mesenchymal stem cells have made significant therapeutic advances with positive clinical results in heart disease, Crohn's, and GVHD.  The question is, "how to improve efficacy?"

Mesenchymal stem cell powerhouse Dr. Darwin Prockup published a recent paper (Lee et al. The CD34-like protein PODXL and {alpha}6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood 2008 Sep 25) that gives us some clues.

They looked for what surface proteins are found primarily in "younger" mesenchymal progenitor cells, that is, what markers are found in the low density, low passage (read this patent about density) compared to older cells.  They found 6 proteins that were detected at a higher concentration on the younger cells, these were: PODXL, CD49f, CD49d, c-Met, CXCR4, and CX3CR1.

PODXL(hi)/CD49f(hi) mesenchymal stem cells produced more differentiated cells as opposed to PODXL(lo)/CD49f(lo) cells when induced to differentiate into various lineages. 

PODXL(hi)/CD49f(hi) cells were not as "embolic" when injected intravenously at high concentrations, and were actually found to engraft at a higher level as opposed to control cells in post-infarct animals.  These data provide some new methods of generating more "potent" mesenchymal stem cells.