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Helping Cultured Stem Cells Roll

May 7, 2010

mesenchymal stem cells with lipid vesicleSpring is here, and for millions of Americans it’s now time to plan for their summer vacations.  First comes the concept – the beach, the mountains, or something more exotic – then comes the practical details of cost, lodging, and transportation that ultimately will make or break their getaways.  As many a frustrated vacation planner will repeat as the choices pile up, “The devil is always in the details.” 

For researchers who study mesenchymal stem cells, the scenario is much the same.  Conceptually, these cells hold enormous therapeutic potential to differentiate on cue into new bone or cartilage-forming cells that can regenerate damaged tissue.  But the devil is always in the details.  One of the trickiest of these details is delivering these cells reliably to a site of injury or inflammation, preferably via direct infusion into the bloodstream.   The problem is typically less than 1 percent of cultured mesenchymal stem cells have the ability to home in on their target once infused into the blood system.  The reason:  In culture, most either lose or do not possess the needed homing receptors that typically must be displayed on the cell surface of mesenchymal stem cells. 

This shortcoming has led to various strategies to coax more cultured mesenchymal stem cells not only to find their targets, but to adhere to them.  That leads to another devilish detail. Mesenchymal stem cells in the blood stream arrive via a rolling landing onto their target tissue. This rolling interaction helps the stem cells to decelerate and, just as importantly, initiate the subsequent steps in the adhesion cascade, including firm adhesion and passage into the tissue.   The problem is current strategies have yet to mimic this natural rolling landing, known as cell rolling, and trigger the natural adhesion cascade.  

But things finally may be rolling into place scientifically.  A team of NIDCR grantees and colleagues previously developed a versatile cell-engineering approach that allowed them to attach adhesion molecules to the surface of stem cells, improving their rolling response and thus homing ability.  Now, as published online in April in the journal Biomaterials, NIDCR grantees and colleagues take the next step in engineering mesenchymal stem cells with self-assembled lipid vesicles on their surface that transiently present molecules that promote cell rolling.  “This method presents an alternative cell membrane engineering approach to introduce a ligand of interest on the cell membrane for short duration, in contrast to enzymatic and covalent modification methods,” they noted.  “Furthermore, this approach offers a platform that can be used to investigate engineered stem cell homing and interrogate the biology of cell homing.” 

  • Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting.  Sarkar D, Vemula PK, Zhao W, Gupta A, Karnik R, and Karp JM. Biomaterials 2010 Jul 31(19):5266-74;Epub 2010 Apr 8.

 

 

 

 

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This page last updated: February 26, 2014