BMP-2 Release By Synthetic Coacervates Improves Bone Making Ability of Muscle Stem Cells


Johnny Huard and his co-workers from the McGowan Institute for Regenerative Medicine at the University of Pittsburgh have isolated a slowly-adherent stem cell population from skeletal muscle called muscle-derived stem cells or MDSCs (see Deasy et al Blood Cells Mol Dis 2001 27: 924-933). These stem cells can form bone and cartilage tissue in culture when induced properly, but more importantly when MDSCs are engineered to express the growth factor Bone Morphogen Protein-2 (BMP-2), they make better bone and do a better job of healing bone lesions than other engineered muscle-derived cells (Gates et al., J Am Acad Orthop Surg 2008 16: 68-76).

In most experiments, MDSCs are infected with genetically engineered viruses to deliver the BMP-2 genes, but the use of viruses is not preferred if such a technique is to come to the clinic. Viruses elicit and immune response and can also introduce mutations into stem cells. Therefore a new way to introduce BMP-2 into stem cells is preferable.

To that end, Huard and his colleagues devised an ingenious technique to feed BMP-2 to implanted MDSCs without using viruses. They utilized a particle composed of heparin (a component of blood vessels) and a synthetic molecule called poly(ethylene arginylaspartate diglyceride), which is mercifully abbreviated PEAD. The PEAD-heparin delivery system formed a so-called “coacervate,” which is a tiny spherical droplet that is held together by internal forces and composed of organic molecules. These PEAD-heparin coacervates could be loaded with BMP-2 protein and they released slowly and steadily to provide the proper stimulus to the MDSCs to form bone.

When tested in culture dishes, the BMP-2-loaded coacervates more than tripled the amount of bone made by the MDSCs, but when they were implanted in living rodents the presence of the BMP-2-loaded coacervates quadrupled the amount of bone made by the MDSCs.

This technique provides a way to continuously deliver BMP-2 to MDSCs without using viral vectors to infect them. These carriers do inhibit the growth or function of the MDSCs and activate their production of bone.

This paper used a “heterotropic bone formation assay” which is to say that cells were injected into the middle of muscle and they formed ectopic bone. The real test is to see if these cells can repair actual bone lesions with this system.

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).