August 2005

From the Lab: Biotechnology

Continued from page 1

By Technology Review

Repairing the Heart
Dividing cells could mend tissue after heart attacks

Results: In a study that could have ramifications for heart attack patients, researchers led by Mark Keating at the Harvard Medical School-affiliated Children's Hospital Boston have coaxed adult mammalian heart muscle cells into dividing by adding two types of chemicals. One blocks an enzyme called p38 MAP kinase, important in the early development of many types of cells; the other comprises protein growth factors. Adding these chemicals to rat heart cells in a lab dish induced 7 percent of them to start dividing. To show that the p38 gene can inhibit heart cell division, the researchers engineered live mice who lacked the gene and found that the duplication and separation of chromosomes in their heart cells -- a key step in cell division -- increased by more than 90 percent.

Why it Matters: During a heart attack, oxygen-starved cells die, leaving behind damaged tissue. Researchers have long thought that the heart can't repair itself because its cells can't divide. This paper suggests that tissue regeneration might be possible. Doctors could potentially administer a drug that triggers heart muscle regrowth in recovering heart attack patients.

Researchers have previously shown that heart cells can divide, but only in strains of lab animals with genetic modifications. Here, the Harvard researchers have shown that they can turn on the cells' ability to divide using a more therapeutically practical strategy: adding chemicals.

Methods: The researchers studied the effects of p38 inhibition on the major stages of cell division -- DNA synthesis, division of the cell's nucleus, and division of the cell itself--in rat cell cultures and living mice. In one experiment, they stimulated heart muscle cells from 12-week-old rats with growth factors in the presence or absence of a p38 inhibitor. They looked for signs of key molecular events associated with the various stages of cell division.

Next Step: While the researchers demonstrated cell division in a lab dish, they did not demonstrate it in live animals. They are now injecting the inhibitor and growth factors into rats with damaged hearts and looking for signs of regrowth. The researchers will also have to ensure that they can control the cell growth and avoid causing cancer. -- By Corie Lok

Source: Engel, F. B., et al. 2005. P38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes and Development 19:1175-87.