CCNA2 Expression Promotes Regeneration in Older Heart Muscle
Researchers here find a potential way to induce greater regeneration in injured heart muscle, normally a tissue that regenerates only poorly following damage, and particularly so in older individuals. Inducing CCNA2 expression appears to promote replication of the cardiomyocyte cells making up heart muscle. Still, a great deal of work remains in order to build a viable gene therapy based on this finding and assess it in a clinical trial. The direct delivery of a gene therapy to heart muscle is perhaps more viable than is the case for other internal organs given the range of established minimally invasive surgical procedures developed for use in the cardiovascular field. One can envisage a therapy that is delivered alongside the procedures normally carried out for patients following a heart attack.
When someone has a heart attack or heart failure, heart muscle cells are lost and the heart cannot replace them. There is no current way to grow new heart muscle cells after damage. Researchers wanted to know if they could reawaken the heart's ability to regenerate itself by using a naturally occurring pathway that enables cardiomyocyte (heart muscle) cell division in utero. They focused on CCNA2 - a gene that is normally silenced after birth - and turned it back on in adults to see if this would help grow new heart cells and help the heart heal.
The research team built a replication-deficient human-compatible virus that carries the CCNA2 gene and delivered it to heart muscle cells. They tested it directly in living adult human heart cells in culture from healthy donor hearts. Researchers used time-lapse imaging to analyze the heart cells with CCNA2 and saw these cells divide successfully, while still keeping their normal structure and function.
More specifically, researchers looked at three healthy hearts from donors who were 21, 41, and 55-years-old. Cyclin A2 therapy triggered these adult human heart cells to divide in the 41- and 55-year-old hearts. Conversely, cells from hearts belonging to a 21-year-old showed no change when given the CCNA2 therapy. This latter finding aligns with previous studies that show younger hearts do have regenerative potential and that their cells are capable of dividing without the stimulus provided by CCNA2.