Sweet Stem Cells

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.

For a link to this story, click here.

Hope for Sickle Cell

Sept. 19, 2014

By Medical Discovery News

While sickle cell disease has long been studied, a recent discovery revealed that the disease significantly increases the levels of a molecule called sphingosine-1-phosphate (S1P), which is generated by an enzyme called sphingosine kinase 1 (SphK1). Inhibiting the enzyme SphK1 was found to reduce the severity of sickle cell disease in mice, which will hopefully lead to new drugs that target SphK1in order to treat sickle cell disease in humans.

Sickle cell disease is caused by a change in the gene that is responsible for a type of hemoglobin, the protein molecule in red blood cells that carries oxygen. This tiny change results in hemoglobin clumping together, changing the shape of red blood cells.

The name for sickle cell disease actually comes from misshapen red blood cells. Rather than being shaped like a disk, or a donut without a whole, sickle cells are shaped like a crescent, sort of bending over on themselves. The normal shape is critical to red blood cells’ ability to easily travel through blood vessels and deliver oxygen to cells and tissues. Sickle cells become inflexible and stick to each other, blocking the flow of blood through blood vessels.

Symptoms of the disease begin to appear at about four months of age. Normally, red blood cells live for about 120 days. Sickle cells only survive 10-20 days. Although the bone marrow tries to compensate for the rapid loss of red blood cells, it cannot keep up. The disease causes pain, anemia, organ damage, and possibly infections.

Although the symptoms and their severity vary, most people with sickle cell disease will have periodic crises lasting hours or days. Symptoms include fatigue, paleness, shortness of breath, increased heart rate, jaundice, and pain. Long-term damage can occur in the spleen, eyes, and other organs, and sickle cell disease increases the risk of stroke. People who only inherit one copy of the sickle cell hemoglobin gene have a milder case of the disease than those who inherit two copies, one from each parent.

Current treatments only reduce the number and the severity of crises using hydroxyrurea, blood transfusions, pain medications, and antibiotics. As the disease advances, dialysis, kidney transplants, eye surgeries, gall bladder removal, and other treatments may be necessary. The only cure for the disease is a bone marrow transplant, which is not an option for everyone.

So it’s pretty exciting that when scientists found that levels of S1P were elevated in mice with sickle cell disease, they inhibited the enzyme SphK1 to reduce the levels of S1P. As a result, red blood cells lived longer and had less sickling. The mice also had less inflammation and tissue damage, which would reduce damage to red blood cells and prevent symptoms of the disease. When they engineered sickle cell disease mice without the gene for the enzyme SphK1 that makes S1P, again the mice had less sickling and symptoms.

How does S1P influence sickling? Apparently, it binds directly to hemoglobin and reduces its ability to collect and carry oxygen, which causes the characteristic folding of cells. S1P has other roles in the body, so it is unknown whether inhibitors to SphK1 can safely and effectively be used in humans to treat sickle cell disease.

For a link to this story, click here.

Giving the Gift of Health

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.”