Shrinking Brains: How Human

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Jessica McConnell Burt / George Washington University

Researcher Chet Sherwood, holding a chimpanzee brain


“We are very weird animals,” said Emory University anthropologist Todd Preuss at the Yerkes National Primate Research Center in Atlanta, who wasn’t involved in the study. “Among neuroscientists, the assumption has been that species are all the same, but this shows there is something really unusual about the late-life biology of the human species.”

It’s estimated that as much as one in every five people in the US will be over the age of 65 by 2030, more than twice the number of elderly just a decade ago, according to the US Administration on Aging. Unfortunately for us, unlike chimpanzees and other primates, elderly humans are vulnerable to a host of neurodegenerative diseases such as Alzheimer’s–the hope of researchers is that understanding the basic biology of the brain can lead to new treatment and measures to postpone the mental demise of aging.

In this study, the first direct comparison of humans to chimps, a team of brain-scanning scientists led by George Washington University anthropologist Chet Sherwood find that chimps don’t experience such memory loss and that humans are uniquely afflicted by this oddity of longevity. They used MRI technology to scan and measure changes in five crucial brain structures involved in memory, reasoning and mental processing, and overall brain volume and density. Measurements were compared from 87 adult human brains (that’s, ahem, a lot of brains) ranging from 22 – 88 years of age with brain volumes of 99 adult chimps ranging from coinciding 10 – 51 years of age. The gray matter of neurons and white matter of connecting neural fibers were also measured. Chimps’ brains were found to only weigh a third as much as the average 3 lb human brain. The 3 lb human brain was found to shrink by up to a surprising 15% in later years.



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The results? “We found no age-related changes in chimpanzees,” said Dr. Sherwood. The human brains lost significant volume over time while the chimpanzees’ remained intact with age. But what humans eventually won’t have in brain volume, they make up for with longevity– a human being can expect to live up to 80 years or more, almost twice the normal lifespan of a chimpanzee in the wild.


“It seems that this is the cost,” said Dr. Sherwood. “We experience more extensive atrophy in the brain that results in this obvious shrinkage, of a kind that is not seen even in our closest relatives, chimpanzees.”

“We were most surprised that chimpanzees, who are separated from humans by only 6-8 million years of independent evolution, did not more closely resemble the human pattern of brain aging,” said Sherwood. “It was already known that macaque monkeys, separated from humans by about 30 million years, do not show humanlike, widespread brain atrophy in aging.”

“This is an excellent example of research that has implications for societal benefits,” said NSF Physical Anthropology Program Officer Kaye Reed. “While Dr. Sherwood and colleagues are interested in the evolutionary significance of brain differences between chimpanzees and humans, the results of this research can be used as a basis to explore degenerative brain diseases, such as Alzheimer’s, in a medical context.”






References:

Hotz, Robert L. “Brain Shrinkage: It’s Only Human.” The Wall Street Journal | Health. Dow Jones & Company, Inc, 26 July 2011. Web. 30 July 2011. http://online.wsj.com/article/SB10001424053111903999904576468224286877908.html.

Plant-Based Compound Effectively & Selectively Kills Cancer Cells

Though cancer cells seem to rebel against orderly cell life and death, breaking all the rules like a misfit, growing wildly and dangerously, there is actually a balance between a cancer cell’s fiery metabolism and skyrocketing levels of cellular stress–it is dependant on a hyperactive metabolism to fuel its rapid growth as well as antioxidant enzymes to rein in potentially toxic reactive oxygen species (ROS) generated by such high metabolic demand.

Long Pepper sw (1).jpgNow a study from scientists at the Broad Institute and Massachusetts General Hospital (MGH) reveals a novel compound that successfully but selectively blocks this response to oxidative stress in cancer cells, sparing normal cells. In fact, its effectiveness surpasses even a chemotherapy drug currently used for breast cancer. The compound? It’s actually derived from the fruit of a pepper plant native to southern India and Southeast Asia, a compound called plant-based piperlongumine or PL. Cancer cells are killed by jamming the machinery that dissipates high oxidative stress and the resulting ROS. Because of their more modest metabolism, normal cells maintain low levels of ROS, making high levels of the anti-oxidant enzymes unnecessary once they pass a certain threshold.

“Piperlongumine targets something that’s not thought to be essential in normal cells,” said Stuart L. Schreiber, a senior co-author and director of the Broad’s Chemical Biology Program. “Cancer cells have a greater dependence on ROS biology than normal cells.”

Some of the best discoveries in history are found by accident, and Sam w. Lee and Anna MAndinova, both senior co-authors from the Cutaneous Biology Research Center (CBRC) at MGH certainly weren’t looking for a ROS inhibitor when they found PL. Their target was in the tumor suppressor gene p53, mutated in more than haf of all cancer types. They were looking for something to increase the levels of the properly functioning p53 gene. A promising signal for PL occurred, but they only assumed it worked by the enhancement of the p53 gene. When PL induced cancer cell death independent of the p53′s activity as the tumor suppressor gene, they sat up and took notice. PL was tested in normal cells – they weren’t killed.



“The novelty of this compound was that it was able to recognize cancer cells from normal cells,” said Mandinova, a Broad associate member and a faculty member at MGH and Harvard Medical School. “It has a mode of action that targets something especially important to the cancer cell.”




And yet another surprise- after the Proteomics Platform’s quantitative analysis identified the target of PL, they found an indirect process on which cancer cells depend, in the stead of the assumed oncogene (a protein encoded by a cancer-causing gene being inhibited). There is a small number of new cancer drugs that target oncogenes directly, but they may not be the only promising new direction for treating cancers. See, cancer genes don’t act alone and PL exploits a dependency developed after oncogenes transform normal cells into cancer cells.

“Our studies suggest that piperlongumine’s ROS-associated mechanism is especially relevant to the transformed cancer cell,” said co-author Andrew M. Stern, associate director of Novel Therapeutics at the Broad. “And this in part may underlie the observed selectivity of PL.”

The scientists tested PL against cancer and normal cells engineered to develop cancer in mice injected with human bladder, lung, breast, or melanoma cancer cells. The PL inhibited tumor growth but showed no toxicity in normal mice. The tougher test of mice that spontaneously developed breast cancer revealed PL blocking both tumor growth and metastasis, whereas the chemotherapy drug paclitaxel (Taxol), even at high levels, proved less effective.



“This compound is selectively reducing the enzyme activity involved in oxidative stress balance in cancer cells, so the ROS level can go up above the threshold for cell death,” said Lee, a Broad associate member and associate director of CBRC at MGH. “We hope we can use this compound as a starting point for the development of a drug so patients can benefit.”




Much more work needs doing to gain a better understanding of how the ROS process differs between normal and cancer cells before the launch of clinical trials. Further studies will focus on different forms of cancer and their genotypes, or genetic information. So while the authors remain cautious, they’re hopeful.

“Our next set of goals is to learn if there are specific cancer genotypes that will be more sensitive to this compound than others,” said Alykhan F. Shamji, associate director of the Broad’s Chemical Biology Program. “We hope our experiments will help be predictive of whether patients with the same genotypes in their tumors would respond the same way. It would help us to pick the right patients.”







Reference:

Cooney, Elizabeth. “Taking out a Cancer’s Co-dependency.” Broad Institute News and Multimedia. Broad Institute, 13 July 2011. Web. 25 July 2011. http://www.broadinstitute.org/news/2979.

Newt Regeneration Unaffected by Ageing


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“She turned me into a newt!”
“A newt?”

“I got better.”

- Monty Python and the Holy Grail (1975)



Armed with the stunning ability to regenerate limbs, eyes, hearts, spinal cords, intestines, and even its upper and lower jaws, newts are the masters of regeneration. Thanks in part to the initial illuminating studies of Italian biologist Lazzaro Spallanzani conducted over 200 years ago, we’ve known for a while that newts and salamanders had this special gift.

As science and technology progressed, biologists learned more about the ability of the cells at the site of the injury to de-differentiate, rapidly reproduce and differentiate again to grow a new organ or limb. But it’s always been unclear the lengths these abilities could stretch to.

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In a study spanning 16 years, Panagiotis Tsonis, along with his team, concludes that the healing ability of newts remain unaffected by injury and age, debunking 250 years of scientific theory about a fundamental element of tissue regeneration – that age and repeated amputation negatively affect regeneration.

As director of the University of Dayton’s Center for Tissue Regeneration and Engineering at Dayton (TREND), Tsonis believes that his discovery will benefit the progressive field of regeneration research, bringing biologists and the medical community one step closer to a complete understanding of the mechanism behind newt regeneration. One day, he believes, humans will be fully able to replicate the process for themselves.

Tsonis’ mentor and co-author of the study Goro Eguchi set up the experiment in 1994, after collecting several Japanese fire-bellied newts (Cynops pyrrhogaster), successfully keeping them in captivity, and over time anesthetising the newts and carefully removing the lenses from their eyes. The team focused on the newt’s lens– it’s unique in that it can be removed entirely and regenerates in a completely enclosed environment after the incision in the cornea heals within a day.

To remove the lens, a small nick to the cornea was made, which quickly sealed, forming a protective environment so that the lens could regenerate without the disruption of any outside influence. And do you know how many times he did this? 18 times in total, with newts that were estimated to be at least 14 years old when collected, making them 30 by the end of the study.

The outstanding thing: The 17th and 18th regenerated lenses of each newt were virtually identical to intact lenses from full-grown newts!

With these repeated surgeries throughout a span of 16 years, and with the oldest newts regenerating their lens as well as the young ones, the team proved the long-held belief that regeneration capabilities are adversely affected with age to be false.

“We are still a long way from relating this to humans, but what this shows is that the newt is an excellent source for finding answers to regeneration, particularly as it relates to old age,” Tsonis said. “The newt not only has good regeneration properties, but it has the ability to protect and preserve regeneration.”

If you haven’t seen him explain newt regeneration himself, check it out here!




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A lens on a young newt that has never undergone regeneration (left) is practically identical to the 17th regenerated lens on an aged newt (right).




“I expected to see regeneration in the final trials, but this good? Even I was surprised a little. It was a perfect lens,” Tsonis said. “As a biologist, I can say this is the biggest discovery in regeneration research involving newts in 250 years.”

The next step? Discover how newts keep their regenerative potential in their ageing tissues so that the new understanding can be applied to human medicine. It won’t be an easy task, since newts and salamanders are notoriously difficult to work with in captivity, but Tsonis’s group are working hard and remain optimistic. “Our findings… are of paramount importance to the field of regeneration and ageing,” Egochi writes.

“We and others have invested a lot of effort to develop these techniques. Many important questions can now be addressed to understand why newts do what they do and how to apply it to regenerative medicine. After all, this animal does everything that regenerative medicine seeks to achieve!”

Join in our efforts to incentivize and accelerate progress in regenerative medicine! Haven’t joined our NewOrgan Network? Sign up for free and get your friends and family on board, too.






References:

Eguchi, Eguchi, Nakamura, Yadav, Milan & Tsonis. 2011. “Regenerative capacity in newts is not altered by repeated regeneration and ageing”. Nature Communications. http://dx.doi.org/10.1038/ncomms1389

“Ageless Regeneration.” University of Dayton News. University of Dayton, 12 June 2100. Web. 20 July 2011. http://www.udayton.edu/news/articles/2011/07/tsonis_regeneration_research.php.

Young, Ed. “Newt Healing Factors Unaffected by Age and Injury.” Discover. Kalmbach Publishing Co., 12 July 2011. Web. 22 July 2011. http://blogs.discovermagazine.com/notrocketscience/2011/07/12/newt-healing-factors-unaffected-by-age-and-injury/.

Whole Teeth Grown From Mouse Stem Cells



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This handout picture taken in 2010 and released to Reuters on July 12, 2011 shows
a bioengineered tooth unit grown by researchers at Tokyo University of Science, using mouse stem cells.
REUTERS/Dr. Takashi Tsuji/Tokyo University of Science/Handout





Here’s something to nosh on– a team of Japanese researchers led by Professor Takashi Tsuji from Tokyo University of Science have constructed teeth out of mouse stem cells and successfully transplanted them into mice!

The team removed two varieties of stem cells from the molar teeth of mice and placed them in a mold to grow in the laboratory, thus controlling its formation – the shape and length of the teeth. Afterwards, the whole tooth units were transplanted into the lower jaws of one-month-old mice. On average, it took 40 days for the transplanted teeth to fuse with the mice’s jaw bones and tissues. Able to detect even the nerve fibers growing in the new teeth, the scientists were able to conduct a very thorough study.

The outcome: The mice with the regenerated teeth were able to eat and chew normally with no complications.

“The bioengineered teeth were fully functional… there was no trouble (with) biting and eating food after transplantation,” writes Masamitsu Oshima, assistant professor at the Research Institute for Science and Technology, Tokyo University of Science.





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Oral photographs (upper) and micro-CT (lower) images showing occlusion of natural (left) and bioengineered teeth (right).
Image credit: PLoS ONE 6(7): e21531. doi:10.1371/journal.pone.0021531





The researchers hope that this step will contribute in the development of new human organs grown from a patient’s own cells.

“It is important to develop technologies for the culture of the bioengineered organ… for the realization of future organ replacement regenerative therapy,” Professor Takashi Tsuji wrote in his reply to questions from Reuters.

Reminiscing about the 2010 US research that led to the construction of an artificial lung that allowed lab rats to breathe for several hours, Tsuji emphasized the necessity of locating the right “seed cells” for reparative therapy. In this case, entire tooth units could be grown because the stem cells were taken from molar teeth of mice, where they later grew into enamel, dental bones and other parts that comprised a regular tooth unit.





References:

Lyn, Tan Ee. “Experts Grow Whole Tooth Units Using Mouse Stem Cells.” Reuters. Thomson Reuters, 12 July 2011. Web. 20 July 2011.
http://www.reuters.com/article/2011/07/12/us-japan-stemcells-tooth-idUSTRE76B4EI20110712.

Braconnier, Deborah. “Stem Cells Grow Fully Functional New Teeth.” Medical XPress. Medical Xpress, 13 July 2011. Web. 20 July 2011.
http://medicalxpress.com/news/2011-07-stem-cells-fully-functional-teeth.html.

How To Live Forever – Mark Wexler Speaks About His New Documentary



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Still from “How To Live Forever” where Jack LaLanne offers director Mark Wexler some exercise advice



This is Mark- the guy to the right. It was a genuine pleasure to chat with Mark. He seems to be one of those real, empathic film makers who work passionately to dignify diverse personalities through film (and is willing to travel the world and live off a suitcase to do it). How to Live Forever, like the rest of his documentaries, stems from a hugely personal time in his life. And, well, what’s the use in us trying to convey the message of the movie when there’s a perfectly good trailer that does it so much better than we ever could?





Can you tell me about the “A-ha” moment when you realized that you wanted to make this film?

When I turned 50 my mom passed away and soon thereafter, my AARP card arrived in the mail and it got me thinking “Hmm, maybe there’s a way to tack more time in. Maybe there’s a way to extend my life, maybe add a whole new chapter to my life or chapters.” So I have a lot of things I want to do and I thought there might be a way to add more time so that set me out on this journey all over the world, initially talking to scientists about how one might extend one’s life. And then it sort of opened up into talking to a variety of people from philosophers to scientists to centenarians, all sorts of different people about how they’re living long and ways that I can live longer. You know, calorie restrictors- the gamut.

I started out the film thinking that I would talk to scientists who would tell me to eat more blueberries, take these supplements and that would give you x amount of years, etc. And I got to talking to people. One of the takeaways from the movie is that it’s not only the length of one’s life but also the quality of living and being able to appreciate it– I think it’s equally important as adding years. So I do still want more years but that may not be the primary goal at this point.


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Poster design by Kajsa Björs





How did you map out your course of documenting the world’s oldest people? How did you know where to start?

At first I knew I wanted to go to the longevity hotspots of the world and I knew one was probably Okinawa, Japan. And I knew that Iceland male life expectancy was long. And there were basically several characters around the world; a guy I filmed named Buster was a 101 year old marathon runner, who was smoking several cigarettes a day and drinking beer still. So I was looking for unusual and quirky characters and my journey around the world involved talking to these centenarians who were unusual for living a long time. So not only was there the longevity hot spots in the world, but the characters, the people– that’s what brought me all over the place.




How long was your journey for?

It took me about 4 years in total to make the film. Some of that, maybe a year and a half in the editing room. And you know, I was cruising the internet, I was talking to people a lot, I would interview someone and ask if they knew someone who knew about calorie restriction and they’d refer me to someone else. There were a lot of referrals but also research, which I love. A lot of it had to be researched well otherwise I’d go halfway across the world and if things didn’t happen exactly the way I wanted, that would have been a very expensive mistake.



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Not everyone we filmed got into the movie, unfortunately, but the movie will have a great extra section just because there are so many interesting characters. We interviewed a 90 year old surgeon who is still performing heart surgery, we interviewed a guy who still flies kites at 100 years old (above) — he builds these amazing kites and still flies them. These are all quite interesting characters who, I think, shared a great sense of humor; the glass is always half full; they have a very positive outlook on life. It was so inspirational to be around these people to be in their presence and they have a sort of inner serenity that is very appealing. I had a great time making the movie because I got to be around these people.


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One of those inspirational figures is SENS‘ own Aubrey de Grey! Who is apparently quite adept at rowing a boat.





It’s clear that the inspiration for your documentaries hugely stem from your personal experiences and values – I think that takes a very special kind of courage. After making How to Live Forever, what are your conclusions about life extension and the world’s pursuit of youth and vigor?

We come from a youth-obsessed culture and I think that’s one of the things I love about Japan, especially Okinawa– elders are really worshipped there and I think there’s a lot to learn from older people. I would love to live longer but I also I want to live well.

I think all the worry about living longer may age me quicker than just enjoying what I have now. I think there are technologies right around the corner that will extend life significantly and that will affect all of society and I think that’s very exciting to realize. But I think there may be consequences good and bad that we can’t imagine that will affect our world, everyone’s world. I also think that as a baby boomer, all of us are interested in packing in more, living longer.




What would you like the audience to come away with?

The subject of aging can be difficult- but most people came away with feeling uplifted and optimistic about where they are in the life cycle so I was happy to impart that to audiences. I hope the movie is thought-provoking and entertaining — it’s also a particularly funny movie. So I was happy to be able to do that. I think having a purpose in life is really key. In Japan there is this thing called Ikigai which is a reason to get up and do your thing– I think that’s key and I think that’s something to nurture. I think we lose that. In Western culture a lot of people retire early and they lose their purpose. And that purpose doesn’t necessarily mean you have to have a job- you know, it can be a hobby that keeps one interested in life. I think people who retire often feel rudderless and that of course affects their health and longevity.

I didn’t expect young people to be interested in the movie- I honestly thought it would only interest baby boomers, people beyond their 40s. But I was surprised to see that young people really enjoyed it, were into it, and I’m pleased by that.

At first I worried that Methuselah Foundation was just all about the numbers- you know, just being alive as long as one can – but I’m glad to know that it’s about having the best quality of life for as long as one can.

So make sure to pre-order your DVDs so you won’t miss out on this awesome documentary– it releases on August 23rd!




New Revenue for Organovo Means Exciting Expansion



Alright. We do a lot of gushing about Organovo. But you know what? With it walking the precipice of cutting-edge, revolutionary technology called bio-printing and its quite impressive strides thus far, we think gushing of geyser-like proportions is warranted… necessary, even. Consider this: Since the founding of Organovo just four years ago, the company has raised over $2 million from private investors and has already developed the bioprinting technology that lays down patterned, cultured cells in a supporting structure of a jello-like hydrogel in a 3-D structure. Which is… you know… phenomenal. And just three years after its founding, Organovo’s NovoGen MMX Bioprinter was named one of Time Magazine’s Best Inventions of 2010. If you don’t think that’s impressive, then you can just stop reading here.


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Their dynamic momentum, with considerable help from the Methuselah Foundation since their beginning has led to the reality of bio-engineered blood vessels and the ambitious plans for kidneys, livers, and other vital organs that are now under way. Armed with a new and, more importantly, stable source of revenue, Organovo is going through expansion of laboratory space to accommodate the size of its ambition! How brilliant is that?! But where’s the moolah coming from?


“Our dance card was full at BIO for partnering meetings, and we’ve got a spectrum of big and small, U.S., Japanese, British, and Swiss pharma companies at the table,” CEO Keith Murphy writes.

“The response to what we’re doing has really been tremendous. People can really use what we have in Oncology, Diabetes, Fibrosis, and other areas where a 3-D [tissue structure] is relevant.”

Murphy has identified a burgeoning market among pharmaceuticals by forming what he calls 3-D “constructs” of diseased or dysfunctional human cells to be used as models for new drug testing. These models react to drug compounds much as they would in the body because the cell matrix enables each cell to interact with adjoining cells (just as it does in the body!). So by producing living human tissue outside the body, the company is making it possible for pharmaceutical researchers to test an experimental compound’s toxicity in a manner that mimics the reaction within a living organism.

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With that in view, two partnership agreements with pharmaceutical companies as well as one made with a regenerative company have been “signed, sealed, delivered” and several other companies are in the works for the same. By the end of this year, Murphy writes, more partnership deals expect to be signed.


“One of the things that’s been good about the past six months is that the promise of our technology is holding true,” Murphy says. “The constructs we’re creating robustly build [blood vessels] with collagen, so the blood vessel grows stronger over time. The next challenge is getting to greater and greater vascularization of the construct. The emerging story is going to be, ‘Who can make thicker tissues with more blood vessels inside?’ “

As Keith Murphy says, creating a made-to-order liver or pancreas in just a few weeks “could happen in 10 years.” The applications continue to advance rapidly. The industry is gaining in heat and momentum. Even in the world of investment, Louis Basenese’s recent recommendation allowed White Cap Report readers to pocket 140% gains in just seven months. Numbers don’t lie and progress is measured in numbers. The public deserves to know that technology like this not only exists outside of science fiction novels, but that we are actively pursuing the day when a complex organ such as a heart or a liver can be printed by a patient’s own cells. Everyone who cares for their own health (and that of their family and friends) deserves to have the opportunity to support this endeavor. (Hint: Think NewOrgan Prize.)





References:

Bigelow, Bruce V. “Organovo’s Bio-Printing Technology Yields Unanticipated Revenue from Pharma Partners.” Xconomy | San Diego. Xconomy Inc., 13 July 2011. Web. 14 July 2011.
http://www.xconomy.com/san-diego/2011/07/13/organovos-bio-printing-technology-yields-unanticipated-revenue-from-pharma-partners/2/.

Fritz, Justin. “Need a New Liver? Just Hit “Print”.” Wall Street Daily. The White Cap Research Group, LLC, 21 June 2011. Web. 14 July 2011. http://www.wallstreetdaily.com/2011/06/21/bioprinting-the-building-blocks-to-print-human-organs/.

Lab-Engineered Trachea Saves A Man’s Life





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June 9, 2011 – A synthetic trachea made up of a 36 year old patient’s own cells was implanted,
saving his life and allowing him to breathe easy, cancer-free
(Photo Credit: David Green)



“He was condemned to die,” said Paolo Macchiarini, a professor of regenerative surgery who carried out the procedure at Sweden’s Karolinska University Hospital. “We now plan to discharge him [Friday].”

For the first time in surgical history, on June 9th 2011, an entirely synthetic and permanent trachea was successfully transplanted using a patient’s own cells. An Eretrian man from Iceland, Andemariam Teklesenbet Beyene, left Karolinska University Hospital in Huddinge, Stockholm Friday breathing through a trachea engineered with cells that came from his own body, not one transplanted from a cadaver’s throat.

As a 36 year old father of two and student of geology at the University of Iceland in Reykjavik, Beyene never imagined that he would suffer from an advanced case of tracheal cancer, experiencing the excruciating difficulty of malignant tumors expanding to about six centimeters in length, almost completely blocking his windpipe and choking off his oxygen supply.

It had reached a point where Dr. Paolo Macchiarini of Karolinska University Hospital decided that there was no time to wait for a donor trachea and assembled a team to build one with Beyene’s own cells. With the successful transplantation of cadaver-based windpipes in 10 patients, he had good reason to feel emboldened. But tracheas from cadavers that are so relied on by patients like Beyene are in very short supply and those who are fortunate enough to receive one face risk of rejection and a life-time of immunosuppressant drugs that also inconveniently include a number of side effects. With a synthetic trachea built from his own cells, Beyene can breathe easy–without the use of the immune-suppressing drugs.

“It makes all the difference,” said Dr. Macchiarini. “If the patient has a malignant tumor in the windpipe, you can’t wait months for a donor to come along.”



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So how did they do it? Scientiest Alexander Seifalian of University College London built the trachea with a glass tube as a base with the precise dimensions of Beyene’s trachea, obtained from three-dimensional images. A medical plastic called polyethylene glycol was then used to build a scaffold around it. Because of the plastic’s porous nature, stem cells can grow into it, induced by the hormones applied by the scientists to persuade them to differentiate into the bony cells- the cells normally found in the lining and exterior of the trachea. Then it’s “popped” into the oven-like bioreactor where after the two days it takes for the cells to grow and proliferate, it’s ready for implantation. From beginning to end, the entire process took less than a week’s time.


The operation marks another step forward for the field of regenerative medicine and “further validates the fact that these technologies may have a role in treating larger numbers of patients in the future,” said Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest University School of Medicine in Winston-Salem, N.C.

48 hours after the procedure, the appropriate cells were shown by imaging and other studies to populate the artificial windpipe which had begun to function like a natural one. Beyene’s immune system did not reject it because the cells came from his own body. In fact, he no longer has cancer and is expected to have a normal life expectancy, the doctors said. His speedy recovery is quite a testament to the mission of making fresh body parts for transplantation or treatment from one’s own cells and more immediately, it offers a viable option for thousands who suffer from tracheal cancer or other life-threatening conditions that affect the trachea.

Dr. Macchiarini says he plans to use the same windpipe-transplant technique on three more patients, two from the U.S. and a nine-month-old child from North Korea who was born without a trachea.

Regenerative therapies are saving more and more lives but there is yet so much ground to cover before much more complex organs like the heart with its many different cell types can be built from a patient’s own cells. We plead you to help us get there faster! Join the New Organ Network for free. Create a profile, build a network of your friends and family. Show that you care!







References:

Naik, Gautam. “Lab-Made Trachea Saves Man.” Wall Street Journal Health. Dow Jones & Company, Inc, 8 July 2011. Web. 8 July 2011.
http://online.wsj.com/article/SB10001424052702304793504576432093996469056.html?mod=googlenews_wsj#articleTabs%3Darticle.

Cevallos, Marissa. “Transplanted Trachea, Born in Lab, Is One of Several Engineered-organ Success Stories.” Los Angeles Times Booster Shots. Los Angeles Times, 8 July 2011. Web. 8 July 2011.
http://www.latimes.com/health/boostershots/la-heb-trachea-transplant-stem-cell-20110708,0,2121263.story.

Functioning Small Intestine Engineered in Laboratory Experiments

A tissue-engineered small intestine in mice that mimics the intestinal structures of a natural intestine was successfully created by researchers from The Saban Research Institute of Children’s Hospital LA on July 5, 2011 in Los Angeles, California. This is a significant milestone toward someday applying this regenerative medicine technique to human beings.


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Tracy Grikscheit, MD The Saban Research Institute of Children’s Hospital Los Angeles
(Photo: Business Wire)




Published as “A Multicellular Approach Forms a Significant Amount of Tissue-Engineered Small Intestine in the Mouse” in the July issue of Tissue Engineering Part A and led by Tracy C. Grisksheit, MD, she explains: “In this paper, we are able to report that we can grow tissue-engineered intestine in a mouse model, which opens the doors of basic biology to understand how to grow this tissue better.”

Those “doors of basic biology” may lead to solutions for Grikscheit’s (a pediatric surgeon) for her more vulnerable patients– premature newborns. These infants are at increased risk for a type of gastrointestinal disease of an unknown cause called necrotizing enterocolitis (NEC) which happens when the intestine is injured. NEC is the most common gastrointestinal emergency in neonates and primarily occurs in premature infants. Unfortunately, rates of prematurity are increasing and so are the numbers of children with NEC.


“The small intestine is an exquisitely regenerative organ. The cells are constantly being lost and replaced over the course of our entire lives,” Grikscheit explains.

“Why not harness that regenerative capacity to benefit these children?”

Why not? Fantastic question. It is crucial to treat NEC early on to prevent bacteria from leaking into the abdomen, potentially threatening the lives of the infants; often the only solution is surgical removal of the small intestine, leaving the baby dependant on intravenous feeding which puts them at risk for liver damage. Transplants are possible but only as a short-term solution, with only 50% chance the grafted intestine will last past the 5th year of the child’s life.

So Griksheit and her research team pressed forward for better options, taking advantage of regenerative techniques. They took samples of intestinal tissue from mice, comprised of the muscle cells and epithelial cells that make up the layers of tissue, then transplanted the cell mixture within the abdomen on biodegradable polymers or “scaffolding”–a word that you will read time and time again in regenerative medical procedures. And voila: brand new engineered small intestines developed and consisted of all the cell types found in the native intestine. The transplanted cells were ingeniously labeled green so that the scientists could identify which cells were provided.


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Illustration of the intestinal tissue regeneration process
Photo: University of Southern California



“What is novel about this research is that this tissue-engineered intestine contains every important cell type needed for functional intestine. For children with intestinal failure, we are always looking for long-term, durable solutions that will not require the administration of toxic drugs to ensure engraftment. This tissue-engineered intestine, which has all of the critical components of the mature intestine, represents a truly exciting albeit preliminary step in the right direction,” said Henri Ford, MD, Vice President and Surgeon-in-Chief at Children’s Hospital Los Angeles.







References:

Kavanagh, Ellin. “Children’s Hospital Los Angeles Researchers Engineer Small Intestine in Lab Research Experiments.” Children’s Hospital Los Angeles. Children’s Hospital Los Angeles, 5 July 2011. Web. 7 July 2011.
http://www.chla.org/site/apps/nlnet/content2.aspx?c=ipINKTOAJsG&b=6089699&ct=10861741&oc=1.

“PIBBS Research Faculty Directory.” University of Southern California. University of Southern California. Web. 7 July 2011. http://www.usc.edu/programs/pibbs/site/faculty/grikscheit_t.htm.

With Your Help, 3-D Bioprinters Will Allow Labs to Grow Replacement Organs

Jewelers, machinists, and chocolatiers. What do these have in common? Just decades-old 3-D printing technology to make custom pieces without having to form molds. Now leading figures in regenerative therapies are using cutting edge 3-D bioprinting to construct living tissue, and perhaps even whole human organs.


In laboratories worldwide, luminaries in biology, chemistry, medicine, and engineering are working on the routes toward one audacious, spectacular goal: to print a functioning human kidney, liver, or heart using a patient’s own cells.

Anthony Atala, NewOrgan Prize Scientific Advisory board member and Director of the Wake Forest Institute for Regenerative Medicine, envisions what he calls “the Dell computer model” where a surgeon could order up “this hard drive, with this much memory…” Except that he/she would be talking about specs for living tissue instead of electronics. What an amazing time we live in!

“The possibilities for this kind of technology are limitless,” said Lawrence Bonassar, whose lab at Cornell University has printed vertebral tissue that tested well in mice. “Everyone has a mother or brother or uncle, aunt, grandmother who needs a meniscus or a kidney or whatever, and they want it tomorrow. … The promise is exciting.”


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Organovo‘s NovoGen MMX Bioprinter
Photo Credit: Organovo


Researchers have already printed skin and vertebral disks and put them into living bodies (yet to be human bodies) but a few types of printed replacement parts such as blood vessels and arterial structures for use in coronary bypass surgeries could be ready for use in human trials in as little as two to five years. In fact, on December 8, 2010 Organovo announced the release of data on the world’s very first fully bioprinted blood vessels from their NovoGen MMX Bioprinter.

“These vessels are the world’s first arteries made solely from cells of an individual person,” said Keith Murphy, Chief Executive Officer of Organovo. “Our results show the power of the NovoGen bioprinting technology to create tissue starting only with cells.”

Aortic valves are the focus of Jonathan Butcher’s lab at Cornell University, with the hopes of printing replacement valves for children with heart disease. Every method of bioprinting differs slightly from one lab to the next. Check out how it’s done at Cornell!


“If the federal government created a ‘human organ project’ and wanted to make the kidney, I literally think it could happen in 10 years,” says chemical engineer Keith Murphy, co-founder of Organovo, a firm that makes and works with high-end bioprinters and a major investment of Methuselah Foundation. “But that would require a massive commitment of people [and] resources”, he said.




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That’s why we at Methuselah Foundation ask you to see the scale of good that this technology can bring to humanity. We ask for the commitment to help realize the goal of making an organ available when the need arises, extending the lives of countless people all over the world. Donate today!





References:

Berkowitz, Bonnie. “3-D Printers May Someday Allow Labs to Create Replacement Human Organs.” The Washington Post National. The Washington Post, 9 May 2011. Web. 4 July 2011.
http://www.washingtonpost.com/national/science/3-d-printers-may-someday-allow-labs-to-create-replacment-human-organs/2011/04/21/AFJM0WbG_story.html.

http://www.organovo.com/

Rapamycin Reverses ‘Accelerated Aging’ in Human Cells

Rapamycin – an immunosuppressant drug used to prevent organ rejection in transplantation – has been found to reverse a very rare, fatal genetic disease called Hutchinson-Gilford progeria syndrome, characterized by very rapid, dramatic appearance of aging.




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Remember our friend and Mprize Lifespan Achievement winner, Dr. David Z. Sharpe? He and his team have already proven that Rapamycin extends the lifespan in healthy mice and now researchers are hoping to uncover new insights into treating progeria and other diseases related to aging.

Published in the journal Science Translational Medicine, a new study finds that Rapamycin can reverse the defects from skin cells of patients with progeria (namely, decreased growth, deformities in their membranes, and early death) by enhancing the cells’ ability to degrade the protein progerin, accumulated in excessive amounts in progeria patients who suffer with issues typically linked with old age: balding, joint pain, hardened skin, hip dislocation, heart disease, and not to mention arteriosclerosis that leads to higher chances of heart attack and stroke.




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Cells taken from progeria patients were treated with the Rapamycin.
Top image shows a toxic protein called progerin (green) spread evenly throughout the cells.
Bottom displays the treated cells with the concentrated protein removed much more effectively.
Credit: Science/AAAS




The findings may have relevance beyond the treatment of this rare genetic disease. Progerin accumulation in normal cells, though not nearly as concentrated as those of progeria sufferers, may still be a factor of the aging process.




Previous research has shown that cellular maintenance failure is a key component of aging. Associate professor of neurology at Harvard Medical School and one of the authors of the paper, Dimitri Krainc indicates that age-related diseases like Parkinson’s and Alzheimer’s also result in defects of the “trash-removal” system of the cells. In simpler terms: Failure of cellular maintenance is a key component of aging.

“With normal aging… you start accumulating by-products of normal cell functions,” says Krainc. Though this study only focused on the effects of Rapamycin on progerin, it may also help clean up other toxic proteins as well.

Dr. David Sinclair, Mprize competitor and director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School, hopes that “the study increases the search for molecules to replace Rapamycin” so as not to have the immunosuppressant side effects. Such alternatives could be a major step forward in the fight against aging.






References:

Scaffidi P, Gordon L, Misteli T (2005) The Cell Nucleus and Aging: Tantalizing Clues and Hopeful Promises. PLoS Biol 3(11): e395. doi:10.1371/journal.pbio.0030395
http://dx.doi.org/10.1371/journal.pbio.0030395.

Vezena, Kenrick. “Drug Reverses ‘Accelerated Aging’ in Human Cells.” Technology Review. MIT Technology Review, 29 June 2011. Web. 1 July 2011.
http://www.technologyreview.com/biomedicine/37916/?p1=A1.