Nature Biotechnology pp 587 - 591, pp 592 - 596 and pp 560 - 561

Researchers have found a way of engineering bone marrow cells in the laboratory so that they don’t lose their ability to grow into all the different cell types that form bone tissue. This approach is needed because of the poor growth of bone marrow cells outside of the body. When cultured in test tubes, marrow cells not only deteriorate and age, but also rapidly lose their capacity to differentiate into all the cell types that make up bone. These problems limit their use as a valuable source of replacement cells for repairing injured or diseased bone.

By adding the human enzyme telomerase reverse transcriptase (hTERT) to marrow cells, two groups of researchers from the United States and Denmark have shown that prolonged culture is possible and that such cultured cells can differentiate into several different types of bone cells in the laboratory. Both groups use a virus to carry into the bone marrow cells the gene encoding hTERT, an enzyme that extends DNA sequences (telomeres) at the ends of chromosomes.

Using this approach, Cun-Yu Wang and colleagues extend the life-span of marrow stromal cells to over 80 population doublings. In another paper, Moustapha Kassem and colleagues expand them even longer (to over 260 doublings). The long-lived cells express proteins on their surface characteristic of cells capable of forming bone, collagen, and adipose tissue. When implanted into immunodeficient mice, the hTERT-expressing marrow cells form more bone than do unaltered marrow cells. The cells also appear to be noncancerous and exhibit a normal set of chromosomes. The studies suggest that hTERT-expressing bone marrow cells may be useful for regenerating bone and possibly other connective tissues.

Nature Biotechnology pp 597 - 601

Antibodies have been isolated that are capable of neutralizing the toxin that makes the anthrax bacterium such a lethal pathogen. Anthrax is a soil microorganism endemic in many parts of the world and infection by inhalation of its heat-resistant spores containing anthrax toxin can result in death rates of up to 80%. The fact that anthrax has been used recently as a means of bioterrorism in the United States means that new forms of anthrax antidotes are needed. In the June issue of Nature Biotechnology, George Georgiou and colleagues report the development of a variety of fragments of a recombinant antibody that are capable of neutralizing the anthrax toxin.

The antibodies work by binding the toxin, thus preventing it from binding its cellular receptor; the antibodies that bind with the highest affinity were found to be the most effective at protecting rats from the effects of the toxin. The work suggests that such toxin-neutralizing antibodies could be promising candidates for alleviating symptoms in patients already infected with anthrax, and could also serve as a medium-term prophylaxis to the infection.

In addition to their high stability in serum (and, by extension, their long half-life inside the body), these antidote candidates also show high stability under heat and in the presence of reagents that typically disrupt protein structure—important factors in terms of the storage, transport, and use of such an antidote in the real world.

Nature Biotechnology pp 613 - 618 and pp 558 - 560

As tomatoes ripen, they become edible and flavorful, but also begin to soften and rot, leading to logistical problems and financial losses for producers and consumers. Genetic manipulation of the ripening process has the potential to extend the shelf life and improve the nutritional quality of tomatoes. A report in the June issue of Nature Biotechnology shows that manipulating the levels of compounds called polyamines can prolong the vine life of tomato fruit.

The mechanisms that control the ripening process of fruit are not fully understood. For some time, polyamines (molecules derived from amino acids, the building blocks of protein) have been suspected to have a role in controlling ripening because they decline throughout the process, and earlier studies have suggested that they can act as ripening regulators.

In their paper, Autar Mattoo and colleagues introduce into tomatoes a gene encoding an enzyme that synthesizes a precursor of two polyamines, spermine and spermidine. By engineering the gene so that it only switches on during ripening, they increased the levels of spermine and spermidine in transgenic fruit. These enhanced tomatoes had longer vine lives, suggesting that polyamines do have a function in delaying the ripening process. Unexpectedly, the fruit also had increased levels of the plant carotenoid lycopene, an increased dietary intake of which has been associated with health benefits such as a reduction in atherosclerosis and lower frequency of some cancers.