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of CKD. Fibrosis is a pathological re- sponse to chronic kidney stress and in- cludes an abnormal buildup of fibrous collagen, a loss of capillaries, a die-off of important kidney cells called tubular epithelial cells, and other changes that progressively reduce a kidney’s ability to filter blood properly.
Researchers found strong hints that the loss of cellular fuel is a driver of the fibrosis process. In mouse mod- els, a drop in fatty acid metabolism preceded the signs of fibrosis. In human tabular epithelial cells, artifi- cially reducing fatty acid metabolism quickly brought about fibrosis-like signs, including the buildup of fat molecules and the deaths of many affected cells.
Fat buildup in kidney cells had been hypothesized to be a significant cause of cell death in CKD fibrosis. But in a mouse model of fat accumu- lation in tubular epithelial cells, Susz- tak showed that the fat accumulation on its own had minimal impact. The more important factor in fibrosis was the loss of energy in the cells as fatty acid metabolism dropped.
Researchers also found evidence that the shutdown of fatty acid metabolism in tubular epithelial cells is caused in large part by the growth factor TGF-ß. The growth factor is known to promote fibrosis and has been linked to high blood glucose levels, high blood pressure, and in- flammation — all triggers of CKD.
When Susztak’s team restored fatty acid metabolism in mouse models of kidney fibrosis using genetic tech- niques or compounds that boost
the activity of fatty acid metabolism genes, the treatment prevented nearly all signs of fibrosis.9
CKD affects at least one in four Ameri- cans 60 years and older and can sig- nificantly shorten a person’s life span.
Breakthrough Biotech
3-D Microtissues May Create Whole Organs
A new device, called the Bio-Pick, Place and Perfuse (BioP3), can print three-dimensional microtissues and may lead to the creation of whole hu- man organs in the future.
Developed by Brown University scien- tist Jeffrey Morgan and Dr. Andrew Blakely, a surgery fellow at Rhode Island Hospital and the Warren Alpert Medical School, the BioP3 applies the precise picking and placing of parts used in electronics manu- facturing. And because it allows assembly of larger structures from small living microtissue components, future versions of BioP3 may finally make possible the manufacture of whole organs, such as livers, pancre- ases and kidneys.
Morgan’s initial research focused on creating individual microtissues in various shapes, including spheres, long rods, doughnut rings and hon- eycomb slabs. A novel micromolding technique directed cells to self-as- semble and form the complex shapes. When stacked, the microtissues natu- rally fuse with each other because they are living components. And by combining the living components, larger tissues can be constructed.
Perhaps even more amazing, the BioP3 prototype was made mostly from parts available at Home Depot for less than $200.
Morgan received a $1.4 million grant from the National Science Founda- tion in September 2014, which will help Morgan and his team make im-
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