Researchers from the University of Illinois at Chicago have got identified a molecular switch that converts skin tissue into cells that make up blood vessels, which could ultimately be used to fix damaged vessels in patients with heart disease or to professional new vasculature in the lab. The technique, which improves levels of an enzyme that keeps cells young, can also circumvent the usual aging that cells undergo during the culturing process. Their findings are reported in the journal Circulation .
Researchers have many ways to convert one type of cell into another. 1 technique involves turning a mature cell into a “pluripotent” originate cell — one that has the ability to become any type of cell — and then using chemical cocktails to coax it directly into maturing into the desired cell type. Other methods reprogram a cell so that it directly assumes a new identity, skipping the stem-cell state.
In the last few years, researchers have begun to explore another method, a middle method, that can turn back the clock on skin cells so they lose some of their mature cell identity and become more stem-like.
“They don’t revert all the way back to the pluripotent stem cell, but instead turn into intermediate progenitor tissue, ” says Dr . Jalees Rehman, associate professor associated with medicine and pharmacology at UIC, who led the particular team of researchers. Progenitor cells can be grown in big amounts sufficient for regenerative therapies. And unlike pluripotent come cells, progenitor cells can only differentiate into a few various cell types. Rehman calls this method to produce new tissue “partial de-differentiation. ”
Other groups used this technique to produce progenitor cells that become blood ship cells. But until now, researchers had not fully understood the way the method worked, Rehman said.
“Without comprehending the molecular processes, it is difficult for us to control or boost the process in order to efficiently build new blood vessels, ” he or she said.
His group discovered that the progenitors could be converted into blood vessel cells or into blood, depending on the level of a gene transcription factor called SOX17.
The researchers measured the levels of many genes important for blood vessel formation. They saw that will as progenitor cells were differentiating into blood boat cells, levels of the transcription factor SOX17 became elevated.
When they increased levels of SOX17 even more in the progenitor cells, they saw that differentiation into blood boat cells was enhanced about five-fold. When they suppressed SOX17, the progenitor cells produced fewer endothelial cells plus instead generated red blood cells.
“It makes a lots of sense that SOX17 is involved because it is abundant in building embryos when blood vessels are forming, ” Rehman stated.
When the researchers embedded the human progenitor tissues into a gel and implanted the gels in rodents, the cells organized into functional human blood vessels. Skin tissues that had not undergone a conversion did not form bloodstream when similarly implanted.
When they implanted the particular progenitor cells into mice that had sustained cardiovascular damage from a heart attack, the implanted cells formed practical human blood vessels in the mouse hearts — and even associated with existing mouse blood vessels to significantly improve heart perform.
The human adult skin cells used by Rehman’s team can easily be obtained by a simple skin biopsy.
“This means that one could generate patient-specific blood vessels or even red blood cells for any individual person, ” Rehman said. Making use of such personalized cells reduces the risk of rejection, he mentioned, because the implanted blood vessels would have the same genetic makeup since the recipient.
Rehman and his colleagues noticed something different about the progenitor cells — they had elevated levels of telomerase — the “anti-aging” enzyme that adds a cover, or telomere, to the ends of chromosomes. As the hats wear away a little bit each time a cell divides, they are thought to contribute to aging in cells, whether in the body or increasing in culture in the laboratory.
“The embrace telomerase we see in the progenitor cells could be an additional benefit of using this partial de-differentiation technique for the production of new arteries for patients with cardiac disease, especially for older individuals, ” Rehman said. “Their cells may already have reduced telomeres due to their advanced age. The process of converting and growing these cells in the lab could make them age even more and impair their long-term function. But if the cells possess elevated levels of telomerase, the cells are at lower risk associated with premature aging. ”
While telomerase offers benefits, the enzyme is also found in extremely high ranges in cancer cells, where it keeps cell department in overdrive.
“We were concerned about the chance of tumor formation, ” Rehman said, but the researchers did not observe any in these experiments. “But to truly determine the particular efficacy and safety of these cells for humans, you need to study them over even longer time periods in bigger animals. ”