Sweet Stem Cells

May 11, 2015 by

May 8, 2015

By Medical Discovery News

Stem Cells

Diabetes may be common, but it’s serious business. Diabetes is repeatedly in the top 10 causes of death for Americans, killing or contributing to the deaths of 300,000 Americans in 2010. An estimated one in 10 people have it, but about one-third of them are undiagnosed. Diabetes costs the country $250 billion. But scientists are working on some good news for diabetics with the help of stem cells.

Type 1 diabetes is largely associated with children and represents about 5 percent of all diabetes cases. The more common form, type 2 diabetes, mostly affects adults and manifests when cells do not use insulin effectively so higher levels are needed (also called insulin resistance). Insulin is a molecule of protein, made and secreted by beta cells in the pancreas, an organ that regulates glucose levels in the blood.

Diabetes is a multifaceted disease that leads to a host of medical conditions and complications, such as high blood pressure, elevated cholesterol, blindness, cardiovascular disease, and kidney problems. Those with diabetes are two times more likely to die of a heart attack and one and half times more likely to die of a stroke. Diabetes is the leading cause of kidney failure, leading to transplants and dialysis. Almost 60 percent of lower extremity amputations are the result of diabetes.

Administering insulin is a common treatment for the disease and there are many different forms that can be used. Insulin can be injected by a syringe or delivered via an automated pump. There are also different pharmaceuticals used in oral treatments for diabetes. Biomedical scientists are developing other methods to treat diabetes, such as transferring insulin-producing beta cells from a donated pancreas into a diabetic patient. This works well, but the cells stop working over time. Transplanting a whole pancreas is also an option that relieves the need to administer insulin, but there is always a short supply of donated organs and the possibility that the new body will reject it.

However, recent stem cell experiments by multiple groups working independently show promise. These cells, called S7, produce insulin and regulate the level of glucose in the blood and successfully eliminated diabetes in an animal model in about 40 days. Unlike organ transplants, there is no limit to the supply of these stems cells, no long wait for a donation that’s a good fit, and no need for immunosuppressant drugs.

But the method is not perfect. First, S7 cells react slower to glucose than natural beta cells and do not make as much insulin. There are also questions as to whether this approach could be used to treat Type 1 diabetes, because the insulin-producing cells are destroyed in an autoimmune process, which might destroy the transplanted cells as well.

It’s premature to claim this innovation is a victory over diabetes, but its development will definitely be worth following.

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Organ Farming

March 15, 2014 by

March 14, 2014

By Medical Discovery News

Imagine that a patient needs an organ, like an airway to their lungs called a trachea. A scientist harvests some of the patient’s cells and attaches them to a scaffold the proper shape and size for the tube. The cells and scaffolds are placed into a tissue reactor and – ta da! – in a week or two there is an organ ready for the surgeon to transplant into the patient. While it sounds like a chapter from “Brave New World,” this science fiction scenario is a growing reality.

Bladders and ears have been grown in the laboratory, and hearts, eyes, and kidneys and other organs are in progress. These organs are close to the natural ones they’re copying – some even have their own immune system. In April 2013, surgeons at the Children’s Hospital of Illinois implanted a bioengineered trachea into a two-year-old child. This was the first surgery of its kind in the United States and one of only six worldwide.

The patient receiving the transplant was a girl named Hannah Warren who was born without a trachea, commonly called a windpipe. Since birth, she’s had a plastic pipe inserted in her mouth that went down into her lungs, allowing her to breathe. She could not eat normally or even speak. With few options available, this type of congenital defect has always meant an early death; only a few children live past the age of six.  

Bioengineered organs could change that. The key is stem cells – cells that are at an early stage of development and through the influence of their environment can produce the many specialized cells of organs and tissues. In this case, doctors harvested the girl’s immature stem cells from the marrow inside her bones. The stem cells were taken to the lab and allowed to adhere to a plastic fiber model precisely the size (about one-half inch in diameter) and structure of the trachea she needed. Once placed in an incubator called a tissue bioreactor, the stem cells colonized the plastic and started growing. While they were growing, cells communicated with neighboring cells and worked together to produce all the cells needed for a functioning trachea. 

At the end of this process, Dr. Paolo Macchiarini implanted the trachea with promising results. Since the cells in the bioengineered trachea were based on ones from her body, her immune system didn’t recognize it as foreign and reject it, a big worry for transplant recipients. Without a plastic pipe in her mouth, Hannah was able to smile for the first time.

Unfortunately, while her trachea functioned well after the surgery, her esophagus never recovered. She underwent a second surgery to fix her esophagus and died from complications. Macchiarini said that her death was not due to the implanted trachea but her own “very fragile” tissue. He called Hannah a “pioneer” in the field of regenerative medicine and plans to conduct similar operations.

The next step for bioengineered organs is clinical trials leading to Food and Drug Administration approval. This would give more scientists and physicians the opportunity to improve organ “farming” and extend this field into a therapy that could benefit many.

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Half Matched Yet Perfect

March 11, 2012 by

By Medical Discovery News

Dec. 31, 2011

Half Matched Yet Perfect

Americans spend much of their time waiting. Waiting in long traffic delays, waiting in line for coffee, waiting for a call back, but not for a lifeline. Yet everyday tens of thousands of people wait for lifesaving organs and bone marrow. Sadly, most die waiting.

Researchers have developed a new procedure that virtually eliminates the wait time for people who need bone marrow transplants. Called “half-matched donors,” this procedure matches a patient with someone whose tissues are only half identical, yet it works just as well as a complete match.

Right now people with leukemia and lymphoma waiting for bone marrow must find a complete match among family members or from a national registry, but more than half never do. As they wait, their cancer progresses and spreads, and many die.

Not that long ago, half-matched, or haploidentical marrow transplants, were considered impossible because of immune system rejection. So, what changed? Immunosuppressive drugs have improved significantly. But it’s not just the drugs themselves; it’s also how they’re used to prepare a patient for marrow transplantation.

In studies at Johns Hopkins Bone Marrow Transplant Program, patients were first put though six days of chemotherapy before transplantation, just enough to suppress their immune system but not harm their organs. On the day of the procedure, half matched donors, who can be a parent, sibling or child, had their marrow extracted by needle from their hipbone. Those without a blood relative were given half-matched umbilical cord blood cells from donors.

Next, researchers injected the donor marrow into the patient and three days later administered high doses of a drug called cyclophosphamide, which re-boots the immune system. The medication kills off the patient’s immune cells but leaves the donated blood cells intact to create a new immune system that is more likely to accept its new host. The new cells also begin creating cancer-free blood cells within 20 days.

Results of these clinical trials show a one-year survival rate of 62 percent for half-identical marrow transplants and 54 percent for half-matched cord blood cells. That is essentially the same success rate for people who receive complete match transplants.

Doctors at Johns Hopkins speculate half-identical transplants work because the recipient’s immune system reacts more strongly against the cancer and lowers the chance of relapse.

In the study’s final phase, doctors will perform haploidentical transplants on nearly 400 patients.  If the results are as promising, researchers estimate that more than half of sickle cell patients, and nearly all patients with blood cancers or autoimmune disorders, will have potential matches.

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Giving the Gift of Health

August 4, 2011 by

Fourteen patients receive kidneys in world’s largest kidney exchange

By Pamela Bond

PennUnion (Johns Hopkins University’s literary journal)

May 6, 2011

 A tragic accident that killed a twenty-four-year-old mother of two became the tipping point that saved fourteen lives and changed thirteen others in 2010.

Jennifer Whitford, of Sebring, Florida, cut her hair and donated it to Locks of Love just days before her death. Her generous spirit is what spurred her mother’s decision to donate her organs.

“If my daughter’s organs can help others, that gives me incredible comfort,” Whitford’s mother, Denise Milliken, said. “She was such a giving young girl. I know she would approve and would be so pleased that her kidney will now allow another mother to finish raising her children.”

Whitford’s family donated her kidneys after her death, starting the world’s largest kidney exchange that occurred in Washington, D.C., from May twenty sixth to June twelfth, 2010. The exchange involved four area hospitals: Georgetown University Hospital, Washington Hopsital Center, Children’s National Medical Center and Inova Fairfax Hospital. Most of the donors and recipients came from the metro area, but some came from as far away as Maine and California.

In the kidney exchange, fourteen people received new kidneys. Whitford was the only deceased donor – the other thirteen donors were living. Receiving a kidney from a live donor greatly increases the amount of time that kidney will function in the new body. It is very hard to find a kidney match. Often, even close blood relatives don’t match.

So, in this kidney exchange, each kidney recipient had someone willing to donate on their behalf, but their kidney actually went to someone else they matched. Each donor was giving a kidney to someone they didn’t know, but in return the patient they were close to received a kidney as well.

Washington, D.C., has the highest per capita occurrence of kidney disease in the nation. Ten percent of the population is on dialysis and two hundred to two hundred and fifty transplants take place each year. Keith Melancon, M.D., director of the kidney/pancreas transplant program at Georgetown University Hospital, said that number should be twice as high.

“People don’t think of kidney disease so much as a life-threatening illness because of dialysis,” he said. “But life-threatening diseases accelerate once you’re on dialysis. And your life span is shorter. If you’re thirty-five and on dialysis, without a transplant you might not make it to fifty.”

Each human has two kidneys, which allows a donor to give one away and still be able to function normally. The kidney serves many functions necessary for survival. Primarily, it filters waste from blood and moves it to the bladder, which is the role dialysis takes when the kidneys fail. But the kidneys also regulate electrolytes and blood pressure, balance acid and base substances, produce hormones, and reabsorb water, glucose and amino acids. Therefore, dialysis is not a perfect solution to kidney disease because it does not replace all the functions of the kidneys.

Currently, more than eighty thousand people are on a waiting list for a kidney in America, according to the United Network for Organ Sharing. About twenty thousand deceased kidney transplants take place every year. The average waiting time for a transplant is two and a half years, but that can range from one month to five years. It’s harder for minorities to find matches and non-whites make up sixty-one percent of those waiting for a kidney, according to the U.S. Department of Health and Human Services.

African-Americans are four times more likely to have kidney disease than whites. This means that many of the people on the waitlist are African-American and there is less of a pool of good kidneys available for transplant. Melancon and Jimmy Light, M.D., director of Transplantation Services at Washington Hospital Center, are trying to change those statistics.

One method they are using is plasmapheresis, which was invented by Charles Drew eighty years ago in D.C. as a way of storing blood. The plasma is removed from the blood. The plasma contains proteins that build antibodies, which are what the body would use to attack a foreign element. This means that a person is more likely to accept a kidney. Normally, the donor and recipient must have many similarities, such as their race, but using plasmapheresis creates more potential donors.

The other method doctors in D.C. are using is these exchanges. The June exchange followed a thirteen-person kidney transplant exchange in December 2009, which held the previous world record. Doctors from different hospitals work together for months to find a donor connected with a recipient, and then find a recipient for that donor. Before Jennifer Whitford’s death, a thirteen-person exchange was planned, but her kidney was a perfect match to a recipient in the program so they were able to use her kidney and add another person.

“Those people literally needed a needle in a haystack,” Melancon said. “Minorities in particular find it extremely difficult to find a suitable donor using traditional donor match methods. By putting them in an exchange and giving them the option of a relatively new use of the blood cleansing technique called plasmapheresis, we can greatly increase their chances of getting a suitable donor as well as reduce their waiting time to get a transplant. In this exchange, five of the recipients received plasmapheresis before and after their transplants.”

Whitford’s kidney went to Brenda Wolfe, age forty-four, of Mt. Airy, Maryland, at GUH. Wolfe is a mother of two just like Whitford. Milliken said it was “amazing” that her daughter would help another mother raise her children.

Wolfe was unexpectedly diagnosed with an autoimmune disorder after a medical procedure last year. She had to be put on dialysis seven days a week and then found out she had renal failure and needed a kidney.

“We came to this exchange and were getting ready for it when I was told I had a perfect match from a deceased donor somewhere in the United States,” Wolfe said. “It was amazing, like I had a perfect twin somewhere.”

Wolfe’s husband, Ralph Wolfe, was already set to donate as part of the exchange when Whitford’s kidney became available. At this point, he had the chance to back out but decided to continue.

“I felt that if I backed out, I’d be going back on my word that I had given to someone I didn’t even know,” Ralph Wolfe said.

Ralph Wolfe’s kidney was removed on June eighth at GUH and transplanted to Gary Johnson, age sixty-three, of Hyattsville, Maryland, at WHC. While Ralph Wolfe is white, he was able to give a kidney to Johnson, who is black, due to the use of plasmapheresis. Johnson has been struggling with diabetes and high blood pressure for decades. His brother donated a kidney to him in 2003, but that only lasted two years before he needed dialysis again.

Johnson’s wife, Jeannette Johnson, age sixty-one, donated her kidney on behalf of her husband to an anonymous recipient, age forty-four, of Arlington, Virginia. Jeannette Johnson is a breast cancer survivor and has been married to Gary Johnson for forty years.

“This particular exchange is a beautiful example of how we need more donors of all kinds and how the different types of donors can come together and make this wonderful life-saving chain,” Melancon said. “Here, we have a deceased donor who started everything off. We have the donors who just donated because they were healthy enough and because they have a deep commitment to their fellow human beings, and you have the directed donors, the family members and friends who came forward on behalf of someone specific they cared about.”

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