Thursday, 12 April 2012 14:05

Sharon Begley´s "Wired" Part I

On this spring afternoon, the 44-year-old CEO of San Diego- based biotech company Cytori Therapeutics pulls out his laptop, launches a PowerPoint presentation, and there they are: conical and cantaloupy. As through Ds, beige and pink and taupe and tan, more breasts than you might see in a women's locker room, never mind in the middle of a lunch table.

A passing waiter does a double take at this lively slide show, but Calhoun is oblivi­ous. He's talking excitedly about how these women's bodies led him and his team of sci­entists to a discovery in tissue engineer­ing, a process that could well be one of the most momentous medical advances of the 21st century: the use of stemcells..... specifically stem-cell enriched adipose (fat) tissue—to enhance, heal, and rebuild injured or damaged organs.

A few taps on his laptop reveal the unsettling "before" images of these seemingly normal breasts. There: a breast with a divot the size of a plum taken out of the bottom from a lumpectomy. There: a chest as flat as a floor mat from a double mastectomy. There: one so misshapen after a partial mastectomy, it's possible to determine what it actually is only because of its healthy companion.

This is a great article, which appeared on October 20, 2010 in Wired Magazine,  although big parts of it are "fiction" from a historic perspective. I got the draft from a friend who apparently got it from somebody who found the draft in an airport lounge and had it on the page before it appeared in Wired. It portrays a lot about the visionary thinking of Cytori and Calhoun in particular, but brings some sobering facts too. Suzanne Begley-as a professional writer- of course got paid for writing it, nonetheless its excellent and one should commend her on a research- and writing job, which was well-done. The original article -no difference- you can find following this link: HERE

"We realized that for these women there was a huge unmet need for a disruptive change in technology," Calhoun says of the work that has consumed his team of researchers and surgeons for the past eight years. "It's the first practical cell therapy." He pauses. "And it's breasts."

Which means cancer victims with breasts mutilated by surgery—as well as women who are simply unhappy with their natural assets—can now grow a new and improved pair, with raw materials harvested from their own body fat. But breast augmentation is just one development (so to speak). in the company's more ambitious plan: to introduce stem cell medicine to the mass market—and not using the ethically fraught kind of stem cells from human embryos. Instead, based on almost a decade of trials that Cytori and its academic partners have performed on cell cultures, lab rodents, and now humans, they believe their engineered flab cells can treat more organs than you find in a French butcher shop.

Chronic heart disease? Check: In human studies released in May, the cells improved patients' aerobic capacity and shrank the size of the infarct (tissue killed by lack of blood).

Heart attack? Check: A human clinical trial, also reported in May, found that the cells increased both the blood supply to damaged heart muscle and the volume of blood that the heart pumped. Kidney injury as a result of cancer therapy?

Check: In recent rat studies the cells improved kidney function. Inconti­nence after prostatectomy ?

Check: Another recent study reported that, by 12 weeks after injewired2ction, the cells had decreased the amount of urine male volunteers were leaking by 89 percent. If Calhoun and his scientists succeed, they won't just create more cleavage. They'll make practical a whole new field, one that medical visionaries have dreamed of for decades: regenerative medicine.
It makes sense to apply Cytori's technology to enhance breasts instead of, say, repair urinary sphincters as a strategic way to move the patented technology out of rats and into people as soon as possible. Hearts, kidneys, and even sphincters have to work in order for us to survive. But we can live just fine without breast tissue, and, outside of feeding offspring, breasts don't have to do much. The fact is, the scientific and regulatory hurdles to getting Cytori's cells into clinical use will be easier to clear for breasts than for other tissue: Breasts simply aren't as necessary as other organs, so the bar for proving to regulators that the technology works will be lower.
It's also a booming market. In 2009, women forked over $964 million to plastic surgeons for breast augmentation, which edges out nose jobs as the most commonly performed plastic surgery in the US.
More is driving that trend than just media-hyped views of beauty. Breast cancer is a major factor. Incidence of the disease has risen from 105 per 100,000 women in 1975 to 125 per 100,000 today (though it peaked at 141 per 100,000 in 1999), and the survival rate has increased: 75 percent of women diagnosed in 1975 lived at least five more years, compared with 90 percent today. That means more women will live more years after a lumpectomy or mastectomy. Most of these survivors would just as soon live those years with something that resembles what they had before, thank you very much. Yet only 30 percent of women facing mastectomy are even offered a consultation with a plastic surgeon, notes Michael McGuire, president of the American Society of Plastic Surgeons and an associate professor of surgery at UCLA. And only 25 percent of women who lose a breast to cancer get a new one. (In 2009, there were 86,424 breast reconstructions.)
There is also demand from a burgeoning demographic no one would have predicted 15 years ago: young women choosing bilateral prophylactic mastectomy after testing positive for mutations in genes-known as BRCA1 and BRCA2—that increase the risk of breast cancer by a factor of five compared with that for women without the mutations. Others are diagnosed with cancer in one breast, have a mastectomy, and decide to have the healthy breast removed as well.

In a 2009 study of women undergoing all forms of surgery for breast cancer, published in -Annals of Surgical Oncology-, by researchers led by surgical oncologist Tod Tuttle of the University of Minnesota, 29 percent opted for this "contralateral prophylactic mastectomy." Among just mastectomy patients (that is, excluding those who had a lumpecromy or other breast-sparing surgery), the rate of taking out the good with the bad was an astounding 56 percent-even though studies find no survival advantage in removing the healthy breast. Yet Tuttle hears it all the time: I never want to go through this again. "Younger and more-educated women are the ones choosing to go this route," he says. And despite the improvements in silicone implants, they're still vulnerable to ruptures and may eventually need to be replaced. What's more, inserting a single implant after cancer surgery can leave a woman asymmetric: It stays put while the surviving breast sags. It's no wonder, then, that women all over the world are desperate for a better option.

HERE'S the WEIRD thing about breasts: They are a point of obsession, vulnerable to the mercurial whims of mass culture. But one thing remains constant: In every era, a whole lot of women are convinced they have the wrong kind.
For better or for worse (mostly for worse), science, or a rudimentary facsimile thereof, has always been eager to help. European women of the 16th century applied a cumin-seed paste with a cloth soaked in water and vinegar to their breasts to keep them small and firm. In the late 1800s, the Princess Bust Developer consisted of a cream and a nifty device resembling a toilet plunger to increase cup size. Starting in the 1940s pinup era, there were liquid silicone oil injections for breast enlargement (bad idea: leakage, inflammation, granulomas) followed, in 1962, by silicone-filled implants.
Given this history of far-fetched augmentation schemes, it's not entirely unfathomable that a plastic surgeon would one day realize the secret to enhanced breasts was hidden in a pair of love handles. In 1999, Marc Hedrick, then an assistant professor of surgery at UCLA, was doing yet another liposuction, and not a little suck-out-a-few-ounces-around-my-thighs-please-doctor procedure, either. He vacuumed 8 liters-more than 2 gallons—of fat from his patient. Scientists had long wondered whether fat tissue might contain stem cells. "If it does, then here we are, stupid plastic surgeons, doing the stupidest procedure on the face of the earth," says Hedrick, 48, now sitting in the La Jolla, California, offices of Cytori, which he cofounded in 2002. "I'd just taken 8 liters out of some woman and dumped it in the trash. I asked myself, are there really stem cells in there?"

 


 

 

Meanwhile, a postdoctoral fellow named Min Zhu had become bored with the rheumatology research she was doing and was looking for a new field. She joined Hedrick's lab in spring of 1999, and he set her to the task of finding out once and for all whether there were stem cells in fat.

Determining the qualities of a stem cell (versus a regular one) requires proving that it can differentiate into many cells, but Zhu hit a brick wall even before she could attempt that: After she isolated candidate stem cells from fat, the things refused to grow, let alone differentiate. Her wired1breakthrough came when she figured out that rather than using the standard fibroblasts as feeder cells in her culture, she would use blood.

"She just brute-forced it," Hedrick says. "She was forging her own trail—with a machete." Using blood to nourish and grow the stem cells, Zhu managed to induce them to differentiate into three lineages: first bone and cartilage, then muscle, and then neuron. She walked into Hedrick's office and said, "I think I have something." In April 2001, the scientists published in the journal Tissue Engineering their discovery that adipose tissue is chock-full of stem cells. At the same time that Zhu was making her break-through, Cytori's Calhoun was running a medical device company called MacroPore Biosurgery, and one of his sales­people told him about a plastic surgeon at UCLA named Marc Hedrick, who was doing some interesting tissue work.

Curious, Calhoun arranged a sit-down with Hedrick. After some pleasantries, the surgeon dropped his bombshell: We've found stem cells in fat tissue. And it's the mother lode. The cells are in the padding around hips, thighs, abdomen, and flabby upper arms in such quantity that it isn't even necessary to culture them—get them to grow and proliferate in lab dishes—to harvest an abundant supply. There is roughly one adipose stem cell per 100 fat cells. (By comparison, bone marrow contains one per 250,000 to 400,000 cells.) "Marc said, we can get these cells out, it has nothing to do with embryos, and their potential is enormous," Calhoun recalls. "I loved him the moment I met him." That love was worth $1 million, the amount of MacroPore's money that Calhoun invested in the company Hedrick was starting, called StemSource3.

By 2002, Calhoun had persuaded MacroPore's board to sell a division of the company to Medtronic, the big medical-device maker, for $21 million. Calhoun turned around and used the cash to buy StemSource, inking the deal in October 2002. (MacroPore changed its name to Cytori Therapeutics in July 2005.) Although StemSource's original business plan had been to bank stem cells, once it had been acquired by MacroPore, the focus switched to therapeutic uses for those adipose stem cells.

Since Hedrick's surgical practice focused on children with facial defects, he thought the cells could be coaxed to make bone in kids with a cleft palate. But as he and his UCLA team did more studies, Hedrick says, "we realized that although the cells could make bone, what they were really good at was making a new blood supply. We felt like if we could target that, it would be the key to every ischemic disease," in which tissue dies for want of an adequate blood supply— and therefore oxygen. "That led us to reconfigure the company to investigate using the cells for heart attack patients." As he and his team conducted rodent studies for heart disease (at one point, Cytori had hundreds of animals in its labs), Hedrick thought if adipose stem cells could yank heart tissue back from death's door by restoring blood flow, maybe the cells could keep other tissue alive and healthy. The radiation that women typically undergo after lumpectomy or mastectomy, for instance, damages the surviving tissue and destroys the local blood supply. "The tissue gets hard, and that makes it difficult to reconstruct or put an implant in," Calhoun says. And thus the idea of using adipose stem cells to reconstruct the breast was born. By 2003, Hedrick and Calhoun were pushing ahead with research on using their stem cells to repair hearts damaged by heart attack or chronic disease. But at the same time, they were grappling with the challenge of repairing patients after partial mastectomy and lumpectomy. It's something that's always been a problem for surgeons: Building only part of a breast with conventional methods, it turns out, is more difficult than constructing a whole new one, because it requires what UCLA's McGuire delicately calls "local tissue rearrangement and/or Haps rather than implants."

In other words, the doctor squeezes and smooshes and moves tissue to fill in divots and missing quadrants and, with luck, turns what might have been reduced to an A cup during a cancer operation into a match for the B or C on the healthy side. The result, alas, can be "very much less than optimal," McGuire admits. "It's difficult to re-create the shape."

And ironically, givwired6en how grateful most breast cancer patients are if they can have a lumpectomy rather than a total mastectomy, such breast-sparing surgery can leave a woman with an aesthetically irreparable breast. With tumors smaller than an inch across, lumpectomy leaves a gouge of up to twice that size, says surgeon Jan Vranckx of Leuven University Hospitals in Belgium: "Breast -conserving surgery is good at keeping the cancer from returning only if it is followed by radiotherapy, but that leaves scars and rigid, badly healing tissue. Yet the defects are often regarded as too small to do a full reconstruction." Calhoun and Hedrick wanted to test their cells on the damaged breasts that other doctors couldn't be bothered with. But Hedrick knew that bringing adipose stem cells into the clinic required more than biology. It also required technology. When Hedrick originally outlined his vision for Calhoun in 2000, he showed him drawings of a device to isolate the stem cells from liposuctioned fat en masse. "We were thinking a box," Hedrick says. "We need some kind of box." After $200 million in R&D, the "box" became the Celution System.

It looks like a souped-up photocopier. But instead of taking in originals and spitting out replicas, it turns liposuctioned fat into breast-making gold. The process to fix a lumpectomy divot begins when a surgeon pierces a patient's tummy with a syringe and sucks out about 360 cc (12 fluid ounces) of fat, which is the pink-orange color of a Pacific sunset. Each syringe takes about five minutes to fill; to treat an average divot requires eight to 10 syringes' worth. The fat is squirted into the Celution device.

A proprietary mix of enzymes digest the scaffolding that holds the tissue together, freeing the cells; the centrifuge separates the adipose tissue from the stem cells, which form a pellet at the bottom of the tube. Those cells are then combined with some of the remaining liposuctioned fat-tissue cells. The result, now a pale pink suspension containing millions of the stem- and regenerative cells, is ready to go. The whole process takes about two hours. It's worth pausing here to ask just what, exactly, these magic cells are. Cytori calls them adipose-derived stem cells, or adipose-derived stem and regenerative cells, and sometimes adipose-derived progenitor cells.

Last modified on Monday, 22 February 2016 11:13

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