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Mar 06, 2014
 |  BC Innovations  |  Targets & Mechanisms

Heart cells: no longer undivided

The inability of adult heart cells to divide rapidly enough to repair cardiac damage has been a major impediment to regenerating heart tissue and preventing fibrosis after myocardial infarction. Now, a U.S. team has used cyclin A2 gene therapy to induce cardiomyocyte division and improve heart function in pig models of myocardial infarction.1

The technology has been licensed to VentriNova Inc., which is planning IND-enabling studies and is seeking investors to fund clinical testing of cyclin A2 (CCNA2) gene therapy to treat MI.

Most mammalian cells regenerate their tissues after injury by undergoing mitosis, but cardiomyocytes do not. Instead, cardiac fibroblasts proliferate after MI. Although they replace the damaged tissue and thus maintain the organ's structural integrity,2,3 they result in fibrotic scarring that compromises heart function and can lead to heart failure.

In the 1990s, studies by multiple groups showed that CCNA2 regulated the cell cycle transitions required for mitosis in many mammalian cell types4,5 but was silenced in mammalian cardiomyocytes shortly after birth.6 Clinical studies have shown that cardiomyocytes undergo a limited degree of turnover-a process by which mitotic cells replace older ones-across the human lifespan.7,8

The unanswered question was whether CCNA2 in adult cardiomyocytes could be reactivated to regenerate heart tissue.

Answers started to emerge in 2004, when a group led by

Debra Wolgemuth at Columbia University engineered mouse embryos to keep Ccna2 active in the heart after birth. The team...

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