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Parkinson’s disease in a dish: Researchers reproduce brain oscillations that characterize the disease
Abnormal oscillations in neurons that control movement, which likely cause the tremors that characterize Parkinson’s disease, have long been reported in patients with the disease. Now, University at Buffalo researchers working with stem cells report that they have reproduced these oscillations in a petri dish, paving the way for much faster ways to screen for new treatments or even a cure for Parkinson’s disease.
The paper is published online in Cell Reports.
“With this new finding, we can now generate in a dish the neuronal misfiring that is similar to what occurs in the brain of a Parkinson’s patient,” said Jian Feng, PhD, senior author on the paper and professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB. “A variety of studies and drug discovery efforts can be implemented on these human neurons to speed up the discovery of a cure for Parkinson’s disease.”
The work provides a useful platform for better understanding the molecular mechanisms at work in the disease, he added.
Will the New Democratic Party or the Liberal Party or the Conservative party of Canada do what is best for Canadians?
Joseph Raglione<human4usbillions@gmail.com>
1:00 AM (2 minutes ago)
to Robert
I can help you win your election but not with money.
Invite people into your party free of charge and listen to their ideas.
List the best ideas and publicize them across Canada.
For examples:
1.Bring Dentists into the Medicare programs and help millions of Canadians save their teeth without emptying their bank accounts.
2. Allow generic drugs to be sold across Canada.
3. Create Green schools across Canada and teach children to grow vegetables within the school classrooms and within the school buildings. Hungry children will learn to feed themselves and learn important life secrets at the same time. Find Stephen Fritz and his Green Machines in New York and he will provide you with full instructions.
4. Create one standard for Electric Car charging stations across Canada and create a government commission to run the stations. All Electric cars sold in Canada must adhere to the standard and the government can charge a small fee for using the stations. In other words, the Canadian government can own and operate the system with funds going back into the government.
Slowly remove gas burning cars from the open market. Fossil fuels are dangerous polluters and only the selfish and ignorant continue to drive these vehicles.
Save
for the occasional burning pain that accompanies a run, most people
don’t pay much attention to the two-leafed organ puffing away in our
chests.
But lungs are feats of engineering wonder: with over 40 types of
cells embedded in a delicate but supple matrix, they continuously pump
oxygen into the bloodstream over an area the size of a tennis field.
Their exquisite tree-like structure optimizes gas exchange efficiency;
unfortunately, it also makes engineering healthy replacement lungs a
near-impossible task.
Rather than building lungs from scratch, scientists take a “replace
and refresh approach”: they take a diseased lung, flush out its sickly,
inflamed cells and reseed the empty matrix with healthy ones.
It’s an intricate procedure—nevertheless, the delicate branches of
blood vessels are often completely destroyed during the process. Without
blood to deliver nutrients and molecules to the newly seeded cells, the
graft fails.
What if, thought Dr. Gordana Vunjak-Novakovic at Columbia University,
rather than removing all cells from a donor lung, we gently clean out
only the diseased cells in the airway without touching blood
circulation?
This week, Vunjak-Novakovic’s team published a “radically new approach” to bioengineering lungs: making scaffolds with blood vessels intact.
When researchers added back therapeutic human cells that line the
lung’s airways to a rat lung scaffold, the foreign cells—in this case,
epithelium cells—homed to the correct location, attached, and thrived.
Because lung failure often stems from diseased epithelium cells, says study author Dr. N. Valerio Dorrello, this new method allows us to regenerate lungs by treating just the injured cells.
Dr. Matthew Bacchetta, who also worked on the project, sees the method as a “transformative”
way to obtain lungs ready for transplant. Because lungs are notoriously
bad at repairing themselves, in severe cases the only real option is a
transplant.
It’s a hard sell—only up to 20 percent of patients are still alive ten years later, the procedure is expensive, and the demand for donor lungs far exceeds the supply.
These new “vascularized” lungs bring us one step closer to the
penultimate goal: transplanting lungs made from a patient’s own cells,
seeded onto a donor scaffold from a cadaver or even primate or pig.
The patients’ cells give the scaffold a complete immune makeover,
lowering the risk of immune rejection—a main reason why transplants
fail.
“As a lung transplant surgeon, I am very excited about the great potential of our technique,” he says.
First Breath
Engineering functional lungs is nothing short of a moonshot, even in the ambitious field of regenerative medicine.
The lung is a real jungle: at the microscopic level, the tree-like
airways contain alveoli, tiny bubble-like structures where the lungs
exchange gas with our blood. Both arteries and veins enwrap the alveoli
like two sets of mesh pockets.
At least a half dozen cellular denizens work in tandem to keep the
alveoli spheres inflated, to guard the organ against infections, and to
enforce the structure of its many branches.
This three-dimensional complexity is why we ruled out the possibility of growing lungs from scratch, explains Dr. Laura Niklason, a biomedical engineer at Yale University who was not involved in the new study.
Back in 2010, Niklason had a brilliant idea: rather than relying on synthetic templates that mimic the organ’s intricate structure—a “very tall order,” she says—scientists could use nature’s own template, the lung’s matrix, as a jumping off point.
Niklason’s approach is similar to stripping down a house to its bare
bones—weight-bearing beams, struts and bolts—and reworking the rest to
its new owner’s tastes.
As a proof-of-concept, Niklason’s team used a detergent that washed
away the cells and blood vessels from a rat lung. They then soaked the
lung matrix scaffold inside a “bioreactor” that mimics the conditions of
a growing fetus.
When the team reseeded the scaffold with a cocktail of cells, the
lung regrew its blood vessels, alveoli and tiny airways with the right
types of cells—all within four days.
In the ultimate test of functionality, Niklason’s team transplanted
the regrown lungs back into living rats. A few seconds later, the lung
inflated, turning bright red as it took in oxygen and blood supply.
It’s just an initial step, the team wrote
at the time. The lungs only survived up to two hours in the donor’s
body, and subsequent analysis revealed bleeding and blood clots within
the airway and regrown capillaries.
One potential reason is this: the blood vessels may not have formed
proper junctions with the alveoli. While still allowing gas exchange,
this eventually causes blood leaks into the lungs.
Breath of Fresh Air
If newly-grown blood vessels form malfunctioned junctions, why not preserve the originals instead?
That’s exactly what Vunjak-Novakovic’s team tackled in the new study published in Science Advances.
Adapting Niklason’s technique, the team inserted a tube into the
airway of a newly harvested rat lung and pumped through a gentle
detergent that only removed the lung’s epithelial cells—the inner
lining.
Blood vessels, in contrast, were washed with an electrolyte solution similar to Gatorade.
With this small change, we removed over 70 percent of epithelial
cells—which are often the root of lung diseases—but maintained the
vasculature, the authors say.
Like cartographers mapping a new land, the team next probed the
integrity of the vessels. Injecting tiny beads that glow under UV light
into the lung’s main artery, they watched as the beads flooded the
twisting capillaries, glowing bright within the larger vessels.
In contrast, there were no obvious signs of glowing beads within the
airway or alveoli, suggesting that the blood vessels were intact—no
leakage!
With scaffold in hand, the team next marinated the structure with
human lung epithelium cells. As a bonus, they also used lung cells
derived from induced pluripotent stem cells (iPSCs). iPSCs are made from
a patient’s own cells—often skin cells—and can be coaxed to become
nearly any other cell type with the right cocktail of signals.
Because iPSCs retain the person’s immune profile, scaffolds seeded with these cells have a much lower chance of being rejected.
Within a mere 24 hours, the team detected signs of the newly seeded
cells within the lung scaffolds. Under the microscope, the newcomers
attached to the right spot, stabilized and begun rapidly dividing to
repopulate the missing cells.
The lung grafts also had a boost in breathing power—they could expand
more fully—gaining back roughly 50 percent of what was lost during the
detergent treatment.
A Breath Away?
The study stops short at the final test: transplanting the engineered
lung back into a recipient. As with older generation scaffolds, the
newly minted lungs could also develop deadly blood clots or bleeding
once reintroduced into a living, breathing animal.
What’s more, the team only used a mild detergent in their preparation
to preserve the lung’s integrity. The result was a partial cleanout
with some of the rats’ own epithelial cells still intact.
These injured stragglers may provide important information to the
new, healthy cells, so this could be an unexpected bonus, the authors explain. Whether they are friend or foe will have to be tested in a future study.
The technology needs a lot more work before it could be used in
humans, but Vunjak-Novakovic and colleagues are already excited about
potential new treatment options.
This study provides proof-of-concept evidence that our approach works, the authors write. We show, for the first time, that it’s possible to wash out diseased lung epithelial cells without touching blood vessels.
What really gets the team excited is this: although freshly harvested
rat lungs were used in this study, in theory the method could be used
without removing the lung.
This is “transformative:”
patients with injured lung epithelial cells could be irrigated with the
detergent to remove the sickly cells. Doctors can then harvest their
skin cells and transform them into healthy lung cells to reseed the
lung.
“Every day, I see children in intensive care with severe lung disease who depend on mechanical ventilation support,” says Dorrello. We may be on our way to an entirely new treatment solution for these patients and regenerate their broken lungs, he says.
Image Credit: N. Valerio Dorrello and Gordana Vunjak-Novakovic, Columbia University
Shelly
Xuelai Fan is a neuroscientist at the University of California, San
Francisco, where she studies ways to make old brains young again. In
addition to research, she's also an avid science writer with an
insatiable obsession with biotech, AI and all things neuro. She spends
her spare time kayaking, bike camping and getting lost in the woods.
If you want to know what I drink during the day, here is my recipe for a Green power smoothie.
1. One cheap and small machine mixer with the power to crush ice. Throw into the mixer jug...
2. One Banana.
3. One Apple.
4. Three hand fulls of baby Spinach leaves.
5. One hand full of chopped Cabbage leaves.
6. One glass of pure Blueberry juice or whatever pure juice you like.
7, One Kiwi
8. Start slow and then mix on high speed until smooth and Green.
9. If you can, try not to drink it all at once, save some for later.
10. Feel the power of the Green curse through your veins and have a great day!