Nature Biotechnology pp 933 - 936

Stem cell researchers in Singapore have come up with a way of growing human embryonic stem cells that allays one of the concerns surrounding the possible development of stem cell therapies for use in the clinic. Human embryonic stem (HES) cells are tricky to grow in the laboratory, readily morphing into different cell types without a supportive cushion of so-called mouse "feeder cells" (mouse embryonic fibroblasts). However, a worry of regulators is that these mouse feeder cells could carry potential human pathogens. Previously, researchers have succeeded in growing HES cells on specially coated plastic minus the mouse cells, but these HES cells were still in contact with solution in which the mouse cells had been grown. In the August issue of Nature Biotechnology, Ariff Bongso and colleagues at the National University of Singapore describe how they avoided all mousy contact by using human feeder cells instead. The researchers cultured fibroblasts from human fetal muscle and skin, and from human adult fallopian tubes. They then used these feeder cells, or the solution in which these feeder cells were grown, to nurture cultures of HES cells. In each instance, the HES cells grew as well, if not better, than they did on plastic plates alone or with the standard mouse feeder-cell system. Importantly, the HES cells retained all the expected characteristics of stem cells. The mouse-free technique could ensure that future HES-cell-based treatments are free of pathogens that could be transmitted to humans.

Nature Biotechnology pp 895 - 900

The ideal cancer drug wipes out tumor cells leaving healthy cells intact—but few achieve such an aim. Now, researchers at The Hebrew University in Jerusalem have devised a strategy to better target drugs to cancer cells--through their Achilles’ heel, genetic mutations. Alexei Shir and Alexander Levitzki describe this novel strategy in the September issue of Nature Biotechnology.

Cancer cells often bear genetic errors, which likely contribute to their aberrant behavior. Common mutations include so-called deletions, in which parts of the genetic code have been lost. To fish abnormal cells carrying deletions out of a sea of healthy cells, the researchers combined antisense techniques with a protein that naturally triggers cell death.

Researchers have long used antisense experimentally to regulate the expression of specific genes: a complementary (antisense) strand of RNA is made, which sticks to messenger RNA (mRNA) preventing its translation into protein. Here, Levitzki and Shir put a new spin on antisense: they designed an antisense strand to a deletion mutation commonly exhibited by cancer cells. The resulting double-stranded RNA molecule then activated the protein kinase PKR, whose role is to scan and kill cells carrying double-stranded RNAs (normally only seen following viral infection). The strategy worked: the antisense sequence triggered the death of an aggressive form of brain cancer cells in culture, and inhibited the growth of brain tumors in mice. Most importantly, the antisense molecule did not damage normal cells.

Although its application in the treatment of human cancers requires further study, this strategy may be used to design beneficial and highly selective cancer therapy.

Nature Biotechnology pp 889 - 894

So-called polyclonal antibodies—natural components of the human immune system—show promise for curing numerous ailments including cancers and infectious diseases. But the only source of these antibodies is human donors, so the supply is very limited. Moreover, it is not safe to immunize patients with dangerous antigens to produce the desired antibodies. In the September issue of Nature Biotechnology, James Robl and colleagues at antibody developer Hematech (Worcester, MA) report that they have cloned calves that produce human antibodies in their blood. To achieve this, the scientists supplemented the animals’ normal genetic material with a synthetic human chromosome carrying the genes for the two proteins needed to form human antibodies. Although human antibodies have been produced before in mice, cows could manufacture much larger amounts.

Several major hurdles must still be overcome before human antibodies from cows could reach the clinic. For example, scientists will need to purify the antibodies away from other cow proteins and to ensure that they are free of viruses.