Blood Vessel Cells Can Repair, Regenerate Organs

Damaged or diseased organs may someday be healed with an injection of blood vessel cells, eliminating the need for donated organs and transplants, according to scientists at Weill Cornell Medical College.

In studies appearing in recent issues of Stem Cell Journal and Developmental Cell, the researchers show that endothelial cells — the cells that make up the structure of blood vessels — are powerful biological machines that drive regeneration in organ tissues by releasing beneficial, organ-specific molecules.

They discovered this by decoding the entirety of active genes in endothelial cells, revealing hundreds of known genes that had never been associated with these cells. The researchers also found that organs dictate the structure and function of their own blood vessels, including the repair molecules they secrete.

Together, the studies show that endothelial cells and the organs they are transplanted into work together to repair damage and restore function, says the study’s lead investigator, Shahin Rafii, M.D., a professor of genetic medicine and co-director of the medical college’s Ansary Stem Cell Institute and Tri-SCI Stem Center. When an organ is injured, its blood vessels may not be able to repair the damage on their own because they may themselves be harmed or inflamed, says Dr. Rafii, who is also an investigator at the Howard Hughes Medical Institute.

“Our work suggests that that an infusion of engineered endothelial cells could engraft into injured tissue and acquire the capacity to repair the organ,” he says. “These studies — along with the first molecular atlas of organ-specific blood vessel cells reported in the Developmental Cell paper— will open up a whole new chapter in translational vascular medicine and will have major therapeutic application.

“Scientists had thought blood vessels in each organ are the same, that they exist to deliver oxygen and nutrients. But they are very different,” and each organ is endowed with blood vessels with unique shape and function and delegated with the difficult task of complying with the metabolic demands of that organ, Dr. Rafii adds.

They found that endothelial cells possess tissue-specific genes that code for unique growth factors, adhesion molecules, and factors regulating metabolism. “We knew that these gene products were critical to the health of a particular tissue, but before our study it was not appreciated that these factors originate in the endothelial cells,” Dr. Nolan says.

“We also found that the healing, or regeneration of tissue, in the liver and in the bone marrow were unexpectedly different — including the repair molecules, known as angiocrine growth factors, that were expressed by the endothelial cells,” says Dr. Olivier Elemento, who performed the complex computational calculations for the studies.

Blood vessels differ among various organs because the endothelial cells have to constantly adapt to the metabolic, biomechanical, inflammatory and immunological needs of that particular organ, says Dr. Michael Ginsberg, a senior postdoctoral associate in Dr. Rafii’s laboratory during this study. Ginsberg also became an employee of Angiocrine Bioscience after the study ended. “And we have now found how endothelial cells have learned to behave differently in each organ and adjust to the needs of those organs,” he says.

These findings raise the question as to how endothelial cells have the capacity to adapt to the biological demands of each organ. Is it possible to design “immature” endothelial cells that could allow scientists to identify the means by which the microenvironmental cues educate them to become more specialized endothelial cells?

The entire article can be read here.

H/T Fight Aging!

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