Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Kidney transplantation is among the major medical advances of the past 30 years. Its major hang-up is still the lack of donor organs. A way around this shortage attempts the use of partially developed kidney precursor cells - nephrons - obtained from early embryos and fetal tissue.

Research immunologists at the Weizmann Institute of Science in Rehovot, Israel, have put this putative approach to in vivo testing. Their interim report in Nature Medicine, released online Dec. 23, 2002, is titled: "Human and porcine early kidney precursors as a new source for transplantation." Transfer into mice revealed the earliest gestational time point at which kidney precursor cells of both human and pig origin differentiate into functional nephrons, and not into other, non-renal professional cell types.

Timing was a key factor. The co-authors achieved successful organogenesis when using the early kidney precursors but not late-gestation organs. The formed miniature kidneys proved functional, as evidenced by the dilute urine they produced. Moreover, transplants of early human and pig kidney precursors showed decreased immunogenicity compared with adult kidney transplants - indicating diminished threat of organ graft rejection.

"In the developing human kidney," their paper recounts, "fresh stem cells were induced into the nephrogenic pathway to form nephrons until 34 weeks of gestation. Thus, transplants of precursors for the adult kidney, present in early embryos and fetal tissue, may be a potential source for regenerating kidney cells, and a promising solution for the current shortage of organs for kidney transplantation."

However, the article noted, "Despite their clinical utility for replacement therapy suggested by murine studies, the fate of undifferentiated and human kidney precursors after transplantation is unknown. The difficulty in obtaining sufficient numbers of human embryos, as well as the ethical problems involved with the use of human embryonic tissue, can be circumvented by the use of porcine embryonic donor tissue."

Accordingly, the team assessed growth potential, vascularization, function and immunogenicity of kidney precursors, derived from both human and pig embryos, after transplantation into both immunodeficient and immunocompetent mouse hosts. "Our findings," they report, "indicate that early in gestation the embryonic kidney contains progenitor cells with the ability to generate multipotent progenitors or embryonic renal stem cells. It has been known for over four decades," the co-authors continued, "that embryonic tissues are less immunogenic compared with their adult counterparts. Thus, our definition of the earliest time point in human or pig renal gestation - at which normal differentiation and subsequent kidney function are possible - may also pinpoint the ideal time for harvesting the tissue less prone to immune rejection. When tested in large animal models or in patients," their paper concludes, "our data predict that these early stage human and pig kidney progenitors should require less immunosuppression compared with that currently used in renal transplantation."

One Glutathione Molecule Devours One Oxidant; One Bilirubin Takes Care Of 10,000 Glutathiones

Bilirubin is not the name of a rock star.

Rather, it's a mystery molecule associated in small quantities with better health, but best known for being at the root of the yellow pigment in jaundice, and at high levels causing brain damage in newborns.

Neuroscientists at the Johns Hopkins School of Medicine in Baltimore have now cracked the enigma of how this toxic pigment can also be beneficial. Their report in the Proceedings of the National Academy of Sciences (PNAS), dated Dec. 10, 2002, appears under the title: "Biliverdin reductase: A major physiologic cytoprotectant." The paper's senior author is Solomon Snyder, director of neuroscience at Hopkins.

The paper makes the point that bilirubin and biliverdin reductase - the enzyme that makes it - conspire to provide the body's most potent protection against damage by reactive oxygen species. Their finding may one day help treatment of stroke, heart attack and even cognitive decline following heart bypass surgery.

"There are some very elegant studies in the literature," Snyder observed, "that tie slightly elevated levels of bilirubin to better alertness in newborns, a lower risk of coronary artery disease, of cancer in adults, and less damage from stroke in animal models. But these findings went against what people thought they knew about bilirubin, and those results were largely shrugged off. Now they make sense."

Known as the toxic yellow molecule at the end of the biologic degradation of hemoglobin - the "red" in red blood cells - bilirubin was known, too, for reacting with the highly reactive forms of oxygen, responsible for practically all cell damage. However, there's so little bilirubin in cells - roughly 1,000 times less than the amount of oxidants - it wasn't thought to contribute to protecting cells.

To test their idea that these tiny amounts of bilirubin had a big gig, the co-authors used RNA interference to "zip up" the RNA for biliverdin reductase. Because that maneuver blocked RNA from making a protein, the effect was knocking out a gene. Thus, deprived of the enzyme, human cancer cells and brain cells from rats experienced much more damage and apoptotic cell death in response to small amounts of hydrogen peroxide, an oxidant, than cells with the reductase intact.

Amazingly, the havoc caused by knocking out the enzyme, and hence bilirubin, was even greater than knocking out the previously known cellular anti-oxidant, glutathione. While it takes one glutathione molecule to consume one oxidant, a single bilirubin molecule took care of 10,000 oxidant molecules. Bilirubin is part of a cycle, so it can use a single molecule over and over again to scavenge the oxygen-free radicals that otherwise would savage cell membranes and their DNA beyond repair.

Despite Five Clinical Trials, Statins Fail Expectations In Reducing LDL Cholesterol

Embargoed until Dec. 20, 2002, an article in the Dec. 1 issue of The American Journal of Medicine reports: "Statins do not meet expectations for lowering low-density lipoprotein cholesterol levels when used in clinical practice." The study, conducted by the Cleveland Clinic Foundation's Department of Preventive Cardiology, investigates the applicability of package-insert guidelines (based on controlled clinical trials) to everyday medical practice.