Arterial Delivery Promising for Muscle Stem Cells

When dystrophin-deficient mice with a disease resembling Duchenne muscular dystrophy (DMD) received an injection of muscle-derived stem cells carrying highly miniaturized genes for dystrophin, the protein needed in DMD, they made more dystrophin than did other mice that received stem cells injected into a vein.

The “microdystrophin” genes were injected into a major leg artery.

Estanislao Bachrach and colleagues at Children’s Hospital in Boston used cells taken from adult mouse skeletal muscles and then further purified to obtain a “side population” that has previously been shown to have muscle progenitor (stemlike) capabilities. The team announced their results online April 21 in Muscle & Nerve.

Earlier studies from this lab, which is directed by long-time MDA grantee Louis Kunkel, have shown that when these cells are injected into a vein, a maximum of 1 percent of the recipient mouse fibers produce the needed dystrophin protein from donor-derived cells.

Based on the expression of microdystrophin or green fluorescent protein (GFP) transgenes in host muscle, sections of the recipient muscles exhibited 5 percent to 8 percent of skeletal muscle fibers.

However, when the cells were injected into the large femoral artery, after the vessel was exposed through a surgical incision, three out of four mice started producing dystrophin in 8 percent of their muscle fibers in one examined section, and one mouse produced dystrophin in 7 percent of its fibers in two sections.

“Our successful delivery of adult muscle progenitor cells to the muscle of dystrophin-deficient [mice] reinforces the utility of intra-arterial delivery of cells as a viable approach for cell-based clinical therapies of primary myopathies [muscle diseases],” the researchers write. “Intra-arterial injection is considered to be a safe, simple and common clinical procedure.”