Lab-grown kidneys

Scientists in Scotland have grown small kidneys--half a centimeter in length, about the size of a fetal kidney-- using a combination of cells from amniotic fluid and fetal cells from animals. The advance follows research published last week creating an early stage retina in the lab.

According to an article in the Scotsman,

"The technique holds out the prospect of scientists being able to collect amniotic fluid at birth to be stored until needed at a later date if a patient develops kidney disease. The patient's own amniotic fluid cells can then be used as the base for creating a new kidney."

"We can make something that has the complexity of a normal, foetal kidney but not an adult one yet," [says physiologist Jamie Davies, a professor of experimental anatomy at the Edinburgh University.] Davies predicts that the technology could be ready for testing in humans in around ten years. Researchers hope to be able to use a patient's own cells, to reduce the risk of an organ being rejected.

Why multi-tasking gets worse as we age

Older people may have more difficulty multi-tasking than their younger counterparts because their brains are less easily able to switch between different networks, according to a brain imaging study published in the Proceedings of the National Academy of Sciences. The findings build on previous research from the same team at the University of California, San Francisco, which showed that older people also have trouble ignoring distractions.

"Our findings suggest that the negative impact of multitasking on working memory is not necessarily a memory problem, per se, but the result of an interaction between attention and memory," senior author of the study, Adam Gazzaley, MD, PhD, UCSF associate professor of neurology, physiology and psychiatry and director of the UCSF Neuroscience Imaging Center, said in a statement from the university.

Researchers used functional MRI to compare brain activity in a group of healthy young people with a mean age of 24.5 and older people with a mean age of 69.1 as they did a visual memory test involving multitasking.

Participants were asked to view a natural scene and maintain it in mind for 14.4 seconds. Then, in the middle of the maintenance period, an interruption occurred: an image of a face popped up and participants were asked to determine its sex and age. They were then asked to recall the original scene.

As expected, older people had more difficulty maintaining the memory of the original image. The fMRI analysis revealed why. When the young and older adults were interrupted, their brains disengaged from a memory maintenance network and reallocated neural resources toward processing the interruption. However, the younger adults re-established connection with the memory maintenance network following the interruption and disengaged from the interrupting image. The older adults, on the other hand, failed both to disengage from the interruption and to reestablish the neural network associated with the disrupted memory.

"The impact of distractions and interruptions reveals the fragility of working memory," said Gazzaley, who also is a member of the W. M. Keck Center for Integrative Neuroscience at UCSF. "This is an important fact to consider, given that we increasingly live in a more demanding, high-interference environment, with a dramatic increase in the accessibility and variety of electronic media and the devices that deliver them, many of which are portable."

In addition to the research studies, Gazzaley's team is exploring the potential of software brain-training programs to help older people improve their ability to mentally process tasks simultaneously. "The ability to dynamically update working memory is critical to cognitive function," he said.

A new source of cancer stem cells

Differentiated breast cells can spontaneously turn into stem cell like cells, according to new research published in the Proceedings of the National Academy of Sciences. The findings challenge the conventional notion that mammalian cells can grow more differentiated but not less. They may also make the hunt for new cancer drugs even more complex.

According to a statement from the Whitehead Institute;

These findings may redefine how researchers view cancer stem cells - the cells capable of seeding new tumors at primary and distant sites in the body. Therapies that specifically target cancer stem cells are currently being investigated in the belief that eliminating cancer stem cells could prevent tumor recurrence and metastasis. However, if cancerous, more differentiated cells can switch between the differentiated and stem-cell states, the more differentiated cancer cells might provide an endless source of new cancer stem cells.

"It may be that if one eliminates the cancer stem cells within a tumor through some targeted agent, some of the surviving non-stem tumor cells will generate new cancer stem cells through spontaneous de-differentiation," says Whitehead Founding Member Robert Weinberg. Cancer stem cells are uniquely capable of reseeding tumors at both primary and distant sites in the body.

"Future drug therapies that are targeted against cancer will need to eliminate the cancer stem cells and, in addition, get rid of the non-stem cells in tumors - both populations must be removed," says Weinberg, who is also a professor of biology at MIT. "Knocking out one or the other is unlikely to suffice to generate a durable clinical response."

Amy Wagers, a researcher at the Harvard Stem Cell Institute and Joslin Diabetes Center in Boston, has retracted a high-profile paper published earlier this year in the journal Nature. According to my Technology Review story on the study,

Researchers surgically connected the circulatory systems of two mice, allowing older animals to be exposed to blood--and all the molecules and cells it carries-- from young animals. They found that the procedure made the blood-forming stem cells in older animals act young again; the overall number of these cells decreased, and the cells generated different varieties of blood cells in more appropriate ratios. "In aged animals, many of the changes we see normally that are associated with age were reversed," said Wagers.

But the retraction, signed by Wagers and two co-authors but not the lead author, says that reexamination of the data led to questions about the role of certain cells in the rejuvenation of in blood-forming stem cells in old mice. The Boston Globe reported that Wagers is now working with colleagues to replicate the experiments.

A clinical trial of Sirtris's drug, SRT501, a potent version of resveratrol, a molecule found in red wine, has been suspended for safety reasons. The company, which was acquired by GlaxoSmithKline two years ago, is developing a number of drugs to combat the diseases of aging. The suspended trial was testing the drug for treatment of multiple myeloma, a blood cancer, in combination with Velcade, a drug that is already on the market.

According to Bloomberg:

Five of 24 patients in the trial developed cast nephropathy, a type of kidney damage that can stem from multiple myeloma and lead to organ failure, said Jo Revill, a spokeswoman for the London-based drugmaker.

However, SRT501 has previously been tested in two other trials for type 2 diabetes, without signs of this complication. It is in development for a number of diseases, including Alzheimer's disease, obesity, and cancer.

A separate class of molecules under development at Sirtris, has also come under fire recently. These molecules, known as sirtuin activators, were named for their reported ability to activate SIRT1, an enzyme thought to play a crucial role in aging. As I noted in a previous blog,

The Pfizer study suggested that resveratrol, a compound found in red wine, and other molecules under development at Sirtris, don't really activate this key enzyme and may not even have the life-extending benefits that have been reported by Sirtris founder David Sinclair and others.