By David N. Leff
Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
Mammalian hair exists in two cyclical growth stages. Anagen hair is growing; telogen hair, resting. Hairs emerge from their roots in the hair follicles, where epithelial stem cells and progenitor cells start them on their way.
A preliminary report of gene therapy as treatment for baldness appears in the April issue of Nature Biotechnology, under the title: "Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex." The authors, research dermatologists at the University of Pennsylvania Medical Center in Philadelphia, harvested transgenes from keratinocytes at the root of hair follicles they plucked.
"At the onset of each new growing stage (called anagen)," their paper explained, "stem cells in the bulge area of the hair follicle proliferate and give rise to progenitor (matrix) cells that subsequently generate the hair shaft."
The team mixed these potential hair-growing cells into the lipid composition of liposomes, then tested this topical "lipoplex" delivery system - first in cell culture, then in the shaved skin of mice, finally in growing human scalp-hair skin surgically implanted under the epidermis of hairless, immunodeficient (scid) mice. These animals were, by definition, unable to reject the foreign donor xenografts.
The approach enhanced the likelihood of successful hair growth in recipient animals by two strategies. Besides closely shaving the 1-centimeter-square recipient skin surfaces, they applied depilatory cream to remove vestigial stubble. Then the co-authors dripped the "lipoplex" mixture onto the graft site every other day for three days. And, their paper pointed out, "Transfection occurred only at the onset of a new growing [anagen] stage of the hair cycle" - the only stage at which hair follicle cells proliferate.
This in vivo procedure, they reported, "resulted in nearly 50 percent transfection efficiency of hair follicle cells. The human hair follicles remain viable for many (more than 12) months, generating abundant normal-appearing human hair.
"Disorders that are candidates for treatment with this approach," the co-authors concluded, "include common [male-pattern] baldness (androgenetic alopecia) and alopecia areata, an autoimmune disorder affecting over 1 percent of the population." (See BioWorld Today, Jan. 30, 1998, p. 1.)
In Search Of Autoimmunity Causes, Data Shift Blame From T Cells To Alien Invaders
Autoimmunity is a major scourge and prime puzzle of modern health and medicine. When the immune system turns against its body's own tissues, it provokes a long litany of autoimmune diseases - from multiple sclerosis and systemic lupus erythematosus to myasthenia gravis to thyroiditis, to insulin-resistant diabetes. Each disease brandishes its own specific antigenic determinants under the noses of immune system B and T cells.
What makes an autoantibody or killer T cell run amok and rain friendly fire on its own body is one of the most hotly researched mysteries in immunology. Normally, the B cells that churn out antibodies to fight invading pathogens practice immune self-tolerance - a hands-off policy, the origin for which many theories exist.
One hypothesis: Those very viruses and bacteria that antibodies and T cells target somehow can break self-tolerance by expressing epitopes that mimic self molecules. Another surmise puts the monkey on the back of the body's own T cells, which somehow - this theory holds - induce the B cells to break their self-tolerance.
A paper in the March 31, 2000, issue of Science refutes this T-cell complicity concept, favoring the foreign-epitope indictment. Its title: "T-cell-independent rescue of B lymphocytes from peripheral immune tolerance." In in vivo experiments, the co-authors injected mice with a bacteriophage (bacterial virus) that expressed an antigen that mimicked a murine self-antigen. Sure enough, the animals' B cells broke their vows of self-tolerance. This result revealed a mechanism by which self-reactive B cells can escape tolerance without benefit of T-cell connivance, thus setting the stage for autoimmune diseases.
3-D Structure Reveals How Key Enzyme Works In 1/30th Of A Second Instead Of 78 Million Years
There's a crucial but laid-back enzyme called OMP decarboxylase that would take 78 million years at room temperature to get a certain key molecule to shed half its carbon dioxide. The OMP stands for orotidine 5'-monophosphate. The molecule, which is central to all life on earth, is UMP - uridine monophosphate.
That OMP enzyme is a critical intermediate in the biosynthesis of cytidine and uridine - two of the four genetic-code nucleosides in RNA. Impairment of this process causes a rare hereditary disorder, orotic aciduria, marked by growth retardation and white blood cell deficiency, among other symptoms.
Five years ago, biochemists at the University of North Carolina in Chapel Hill re-jiggered OMP to do its stuff 30 times a second, rather than taking 78 million years. Now, in collaboration with Glaxo Wellcome Inc. in Research Triangle Park, N. C., they have solved the enzyme's 3-dimensional crystalline structure. Their report appears in the Feb. 29, 2000, issue of the Proceedings of the National Academy of Sciences (PNAS). Its title is "Anatomy of a proficient enzyme: The structure of oratidine 5'-monophosphate decarboxylase in the presence and absence of a potential transition state analog."
When Plant Seed Pods Burst Prematurely, Crops Spoil; Mutant Genes Prevent Process
To surgeons, the word dehiscence means what happens when a sutured incision breaks its stitches and splits wide open. To farmers, dehiscence occurs when seed pods break open prematurely and spill their contents. In important oilseed crop plants, such as rape (Brassica napus) or canola (Brassica rapa), up to half the yield can be lost by premature pod-shattering.
Developmental biologists at the University of California-San Diego looked at two mutant genes - Shatterproof 1 and 2 - that forestall this wasteful process, and so retain their seeds. Their report, in the April 13, 2000, issue of Nature, carries the title: "SHATTERPROOF MADS-box genes control seed dispersal in Arabidopsis."