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Biological Chemistry

Chemical cocktail induces fibroblasts to become heart cells

Converted collagen-producing skin cells help repair cardiac damage in mice

by Elizabeth K. Wilson
May 2, 2016 | A version of this story appeared in Volume 94, Issue 18

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Credit: Science
This immunofluorescence image shows chemical markers identifying a fibroblast that has been converted to a cardiac-like cell. The inset shows areas at higher magnification.
A colorful micrograph image of modified fibroblast cells
Credit: Science
This immunofluorescence image shows chemical markers identifying a fibroblast that has been converted to a cardiac-like cell. The inset shows areas at higher magnification.

Researchers have found that giving fibroblasts a bath in a mixture of nine chemicals can convert the collagen-producing skin cells into cardiac-like cells. A long-held goal, this type of cellular manipulation could give surgeons a source of tissue to help repair damage after a heart attack. A team led by Sheng Ding of the University of California, San Francisco, developed the method and has shown that the new cardiomyocytes, which are muscle cells that help the heart beat, can repair cardiac damage in mice (Science 2016, DOI: 10.1126/science.aaf1502). Researchers have been attempting to accomplish this fibroblast-to-cardiomyocyte conversion by a variety of methods, most notably through genetic manipulation. However, the yields have been poor. Ding’s group selected 83 compounds, which included enzyme inhibitors and epigenetic modulators known to help reprogram cell growth and development, to steer the cells toward cardiac function. The researchers exposed human foreskin fibroblasts to various combinations of the compounds, finding that one set of nine compounds accomplished the conversion to cardiac-like cells with beating behavior. They then transplanted the cells into mice with cardiac damage similar to that caused by heart attacks. Two weeks later, the rodent’s heart function had improved.

BLUB DUB
his video shows the beating of a cardiac-like cell, 40 um across, which was created by exposing a human skin cell to a cocktail of nine chemicals. Video is at three times speed.
Credit:Nan Cao/Gladstone Institutes

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