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Some good news science – growing spare parts for people

With all the corruption and failures in climate science, sometimes it’s nice to read about how some areas of science are still working, and developing something that matters.

There are thousands of people working on a frontier of science that promises to revolutionize medicine. We are living in the last days of what we’ll come to know as the “old medicine” where surgeons do the unthinkable — cutting out healthy blood vessels to get spare parts for more important sites, or treating people with drugs that affect cells all over the body (with many unwanted side-effects) when what we need is a way to get the right molecules into a tiny percentage of cells. Then there is the devastating cost of using transplants from other people (deceased or not), and then having to use immune-suppressant drugs for life. Growing your own spare parts — customized and make to order — is the brilliant alternative.

Our lives would be so much better if the money used to install vast inefficient solar arrays, or bird-breaking windfarms was used instead on gene therapy. That doesn’t mean everything about this is unquestionably good, like any powerful tool, gene therapy can kill as well as save. That’s why we need to do the research, and the sooner the better.

Virtually all our cells contain all the genes that make us. So if we learn how to switch the right genes on and with the right timing, in theory, with the right scaffolding, we can build any body part. Growing a full liver is a long way off, but it’s coming. We are at the stage of building simple parts like bladders and blood vessels.

To give you some idea of how huge this field is, here are just a few stories released in the last week: Making new blood vessels from fat cells, turning skin cells into the neurons that are affected by Parkinsons, and figuring out which genes are involved in growing new teeth.

Adult stem cells from liposuction used to create blood vessels in the lab

[American Heart Association]

NEW ORLEANS — Adult stem cells extracted during liposuction can be used to grow healthy new small-diameter blood vessels for use in heart bypass surgery and other procedures, according to new research presented at the American Heart Association’s Basic Cardiovascular Sciences 2012 Scientific Sessions.

Millions of cardiovascular disease patients are in need of small-diameter vessel grafts for procedures requiring blood to be routed around blocked arteries.
These liposuction-derived vessels, grown in a lab, could help solve major problems associated with grafting blood vessels from elsewhere in the body or from using artificial blood vessels that are not living tissue, said Matthias Nollert, Ph.D., the lead author of the study and associate professor at the University of Oklahoma School of Chemical, Biological and Materials Engineering, in Norman, Okla.
“Current small-diameter vessel grafts carry an inherent risk of clotting, being rejected or otherwise failing to function normally,” Nollert said. “Our engineered blood vessels have good mechanical properties and we believe they will contract normally when exposed to hormones. They also appear to prevent the accumulation of blood platelets — a component in blood that causes arteries to narrow.”
In this study, adult stem cells derived from fat are turned into smooth muscle cells in the laboratory, and then “seeded” onto a very thin collagen membrane. As the stem cells multiplied, the researchers rolled them into tubes matching the diameter of small blood vessels. In three to four weeks, they grew into usable blood vessels.
Creating blood vessels with this technique has the potential for “off-the-shelf” replacement vessels that can be used in graft procedures, Nollert said.
The researchers hope to have a working prototype to test in animals within six months.
Co-authors are Jaclyn A. Brennan, M.S., and Julien H. Arrizabalaga, B.S. Author disclosures are on the abstract. Funding for this study was provided by the American Heart Association.
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Then here is news about skin cells being turned into brain cells – the aim is to get exactly the right cells growing in the lab to test drugs and treatments for Parkinson’s, but eventually  (several steps and many years down the track) this could lead to a cure. So far researchers have had to test treatments on mice, and have “cured” mice, but mice are not men, and Parkinson’s in mice is not the same as Parkinson’s in people. Half a million people in the US suffer from Parkinson’s. News here suggests though that the best chance of stopping the damage is in the early stages, before symptoms start. But in the long run, I can imagine they might find ways to repair damaged cells.

Researchers Turn Skin Cells Into Brain Cells, A Promising Path To Better Parkinson’s Disease Treatment

[John Hopkins]

July 17 2012: “Parkinson’s in a dish” should advance hunt for new drugs or earlier use of older ones

Neuron. Image by Nicolas P. Rougier

Using adult stem cells, Johns Hopkins researchers and a consortium of colleagues nationwide say they have generated the type of human neuron specifically damaged by Parkinson’s disease (PD) and used various drugs to stop the damage.

Their experiments on cells in the laboratory, reported in the July 4 issue of the journal Science Translational Medicine, could speed the search for new drugs to treat the incurable neurodegenerative disease, but also, they say, may lead them back to better ways of using medications that previously failed in clinical trials.

“Our study suggests that some failed drugs should actually work if they were used earlier, and especially if we could diagnose PD before tremors and other symptoms first appear,” says one of the study’s leaders, Ted M. Dawson, M.D., Ph.D., a professor of neurology at the Johns Hopkins University School of Medicine.

Dawson and his colleagues, working as part of a National Institute of Neurological Disorders and Stroke consortium, created three lines of induced pluripotent stem (iPS) cells derived from the skin cells of adults with PD. Two of the cell lines had the mutated LRKK2 gene, a hallmark of the most common genetic cause of PD.

Induced pluripotent stem cells are adult cells that have been genetically reprogrammed to their most primitive state. Under the right circumstances, they can develop into most or all of the 200 cell types in the human body.

In the laboratory, the consortium scientists used the iPS cells to create dopamine neurons, those that bear the brunt of PD. Around age 60, people who have the disorder typically begin to show symptoms, including shaking (tremors) and difficulty with walking, movement and coordination. In the United States, at least 500,000 people are believed to have PD, and an estimated 50,000 new cases are reported annually.

Note below, the talk about mitochondria — many things in aging come down to problems with these tiny parts of cells — the parts where energy is made to power everything else in the cell. These are the “batteries” inside cells where the heaviest chemical work goes on — the parts where sugars are burnt with oxygen to produce energy and CO2. By default, they also generate many free radicals and bear the cost of dealing with highly reactive molecules.

Dawson says the ability to experiment with a form of “Parkinson’s in a dish” should lead to further understanding of how the disease originates, develops and behaves in humans. Although scientists have been able to stop the disease in mice, the compounds used to do so have not worked in people, suggesting that human PD behaves differently than animal models of the disorder. Dawson, director of Johns Hopkins’ Institute for Cell Engineering, says the researchers began with the belief that PD is strongly linked to disruption of the dopamine neurons’ mitochondria, the energy-making power plants of the cells. Mitochondria undergo regular turnover in which they fuse together and then split apart. Normal neurons make new mitochondria and degrade older mitochondria in a balanced way to supply just the amount of energy needed.

PD, Dawson says, is believed to damage this system, leaving too few functional mitochondria and producing too many brain-damaging oxygen-free radicals.

Dawson and his colleagues looked for — and found — evidence of impaired mitochondria in the neurons they derived from PD patients. They also found that the neurons they generated from PD patients were more susceptible to stressors, such as the pesticide rotenone, placed on them in the lab. Those neurons were more likely to become damaged or to die than the neurons derived from the skin of healthy individuals.

Satisfied that their stem cell-generated neurons were behaving like dopamine brain cells, the scientists next set out to see if they could slow the damage occurring in the PD neurons by introducing various compounds to the cells. They tested Coenzyme Q10, rapamycin and the LRRK2 kinase inhibitor GW5074, all of which are known to reverse mitochondrial defects in animals. The cells responded favorably to all three treatments, preventing stressors from continuing to damage the mitochondria.

Dawson says more than 20 clinical trials have been conducted in people with PD using drugs designed to slow the disease’s progression. All of them have failed. Coenzyme Q10 worked in the iPS cells derived from PD patients. “This suggests the need to treat people before they actually manifest the disease,” he says. Dawson cautioned that the consortium’s work is at its earliest stages, and that application of the findings may be years away. Among other barriers, he says, is the lack of a way to diagnose PD before tremors and other symptoms appear. In addition, although several gene mutations have been linked to PD, there could be more, making a simple genetic test for the disease unlikely in the near term. Moreover, the majority of PD has no known specific genetic link.

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One day no one will get a crown from their dentist — they’ll just replace teeth with new ones — or possibly grow them right in your mouth. This is still a long way off — this study reports that they have found one key factor in the sequence that helps a mouse keep its front teeth growing continuously for life. We don’t know yet if this is the same sequence in human embryonic development.

One Step Closer to Growing a Tooth

In a three year old human (above) the adult teeth have already formed and are waiting to come down. In a mouse the front teeth grow continuously.

July 18th: Researchers in the group of Professor Irma Thesleff at the Institute of Biotechnology in Helsinki, Finland have now found a marker for dental stem cells. They showed that the transcription factor Sox2 is specifically expressed in stem cells of the mouse incisor (front tooth). The mouse incisor grows continuously throughout life and this growth is fueled by stem cells located at the base of the tooth. These cells offer an excellent model to study dental stem cells.

The researchers developed a method to record the division, movement, and specification of these cells. By tracing the descendants of genetically labeled cells, they also showed that Sox2 positive stem cells give rise to enamel-forming ameloblasts as well as other cell lineages of the tooth.

– Although human teeth don’t grow continuously, the mechanisms that control and regulate their growth are similar as in mouse teeth. Therefore, the discovery of Sox2 as a marker for dental stem cells is an important step toward developing a complete bioengineered tooth. In the future, it may be possible to grow new teeth from stem cells to replace lost ones, says researcher Emma Juuri, a co-author of the study.

read more about the work by the University of Helsinki

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REFERENCES

American Heart Association (2012, July 25). Adult stem cells from liposuction used to create blood vessels in the lab. ScienceDaily.
O. Cooper, H. Seo, S. Andrabi, C. Guardia-Laguarta, J. Graziotto, M. Sundberg, J. R. McLean, L. Carrillo-Reid, Z. Xie, T. Osborn, G. Hargus, M. Deleidi, T. Lawson, H. Bogetofte, E. Perez-Torres, L. Clark, C. Moskowitz, J. Mazzulli, L. Chen, L. Volpicelli-Daley, N. Romero, H. Jiang, R. J. Uitti, Z. Huang, G. Opala, L. A. Scarffe, V. L. Dawson, C. Klein, J. Feng, O. A. Ross, J. Q. Trojanowski, V. M.- Y. Lee, K. Marder, D. J. Surmeier, Z. K. Wszolek, S. Przedborski, D. Krainc, T. M. Dawson, O. Isacson. Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson’s Disease. Science Translational Medicine, 2012; 4 (141): 141ra90 DOI: 10.1126/scitranslmed.3003985
Emma Juuri, Kan Saito, Laura Ahtiainen, Kerstin Seidel, Mark Tummers, Konrad Hochedlinger, Ophir D. Klein, Irma Thesleff and Frederic Michon. Sox2 Stem Cells Contribute to All Epithelial Lineages of the Tooth via Sfrp5 Progenitors. Developmental Cell, July 19, 2012
h/t ScienceDaily
Images: Blood VesselNeuron Wikimedia | Teeth: JoNova
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