Fight Aging!

Cell therapies have shown some ability to reduce fibrosis, the generation of scar-like structures in place of functional tissue that appears with aging and a variety of forms of organ failure. Fibrosis is one of the consequences of growing numbers of senescent cells and the chronic inflammation they cause. The normal intricate coordination of cell populations in regeneration and tissue maintenance runs awry. Cell therapies may help by pushing the balance of cell signaling back towards a more youthful, normal pattern, and reducing inflammation, at least for a time. This doesn't appear to be as be as potentially beneficial as clearance of senescent cells, but the development of cell therapies is a much larger and more mature field. The research here is one example of a more sophisticated effort to adjust the cellular environment to induce regeneration by transplanting cells of a specific type to induce the desired signaling changes.

Scientists have been exploring the potential of stem cell and other cell therapies to regenerate fibrosis-damaged organs including cirrhotic livers. One problem with this strategy is that inflammatory and other disease processes within a damaged organ tend to create an inhospitable environment - or "niche" - for transplanted cells and even for resident stem cells. Prior work has shown, however, that vessel-lining endothelial cells can produce special organ-specific growth factors, known as angiocrine factors, that restore a healthier niche and promote regeneration without provoking scarring. "In the case of liver cirrhosis, blood vessels in the liver are damaged and fail to supply angiocrine factors that promote regeneration. So the idea underlying this endothelial cell therapy is to rejuvenate that vascular niche. Accordingly, the remaining hepatocyte progenitors in the liver can get the proper signals from angiocrine factors they need to suppress fibrosis and regenerate liver tissue."

For the study, the investigators harvested small quantities of endothelial cells from the liver vessels of eight pigs, and multiplied the cells to large quantities in the laboratory. After inducing cirrhosis in each pig's liver, the researchers then treated half of the pigs by infusing the liver-specific endothelial cells into a large vein that runs into the liver, using a small catheter inserted through the skin and guided by ultrasound and live X-ray imaging.

Although the number of pigs in the study wasn't large enough to determine the therapeutic effectiveness of the technique, examination of the pigs' livers three weeks after treatment revealed some striking differences between treated and untreated animals. When the investigators examined samples of cells and tissues taken from the treated pigs' livers under the microscope, they found that the organ appeared much more like the livers of healthy pigs, in contrast to the untreated livers. The researchers now hope to conduct larger trials of the endothelial cell therapy in pigs and, if they are successful, progress to clinical trials in humans. In principle the cell therapy could be used to treat not just cirrhosis but other forms of liver injury as well.

Link: http://news.cornell.edu/stories/2017/10/infusion-vascular-cells-treat-liver-cirrhosis-shows-promise