From Connective-Tissue Cells to Heart Cells With No Stops In Between
In January, we discussed a biotech first–a transformation from skin cell to brain cell, without reverting to a more mutable stem cell in between. Today a paper in the journal Cell describes a similar direct transformation in mice, from a type of structural cell called a fibroblast to heart cells. If one day scientists can entice human cells to make a similar “direct conversion,” the researchers believe this metamorphosis may prove one way to fix heart damage that’s irreparable under the current state of medicine.
The study’s authors at the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco, once attempted to use stem cells for heart repair with little success, Nature News reports. Though the stem cells quickly turned into the beating variety, called cardiomyocytes, they remained feeble, never transforming into the strongly beating muscle cells of a healthy heart.
“I don’t know that this [direct conversion] will entirely replace stem cells,” says Deepak Srivastava [lead author on the study]… “But it will offer another strategy that might remove some of the concerns of using stem cells.” [Nature News]
The stem cell failure spurred the team to study the cardiomyocytes in more detail, searching for proteins that activate the genes responsible for making cardiomyocytes in mice embryos. They found three essential proteins and their associated genes: Gata4, Mef2c, and Tbx5. After activating these genes in adult fibroblasts and implanting them back into the mice, within a day, the cells started to transform into the coveted cardiomyocytes. Eventually 20 percent converted.
“Scientists have tried for 20 years to convert nonmuscle cells into heart muscle, but it turns out we just needed the right combination of genes at the right dose,” [study coauthor Masaki] Ieda, now at the Keio University School of Medicine in Japan, said in a statement. [Reuters]
Though Srivastava cautions that researchers must first show that human fibroblasts can use the same proteins to make the switch, he told The Telegraph that instead of removing cells, modifying them, and reintroducing them, as his team did in the mouse study, they might instead find a way to activate the conversion genes using a medication added through a tube, called a stent, in the coronary artery:
“It is ambitious, but not unreasonable, to imagine being ready for a clinical trial in the next five years.” [The Telegraph]
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