You’re More Like Your Mother Than You Know

May 24, 2015 by

May 22, 2015

By Medical Discovery News

Photo of mother and child

While the benefits of breast feeding have been well-documented, scientists were surprised to learn of another one: breast milk contains a mother’s stem cells that become a part of different organs of the baby’s body.

Breast feeding protects infants against infections early in life and reduces their risk of juvenile diabetes, heart disease, and cancer as children. It also helps mothers lose weight after giving birth and lowers their risk of osteoporosis and uterine and ovarian cancer.

In addition, seven years ago scientists discovered the presence of mammary stem cells in breast milk. The mammary gland is unique in its ability to go through different stages in anticipation of producing milk, then a period of milk secretion followed by a return to the non-lactating state. All of this can occur as many times as necessary. This massive restructuring of the breast suggested the presence of stem cells.

Human breast milk contains about 14,000 cells in each milliliter. Most of these are the epithelial cells that are abundant in the breast and cells of the immune system. Some of the cells in breast milk had a molecule called nestin on the surface, which in adults is a marker for multipotent stem cells that can develop into many different types of cells, like those in the brain, pancreas, liver, skin, and bone marrow. When scientists transplanted a single nestin-positive stem cells into the fat pad of a grown mouse, it reconstituted a functional mammary gland. Scientists wondered if such cells were serving the same function in humans.

However, further research revealed quite a surprise. First, they genetically modified mice to produce a protein that makes the cells glow red under fluorescent light. Mothers with this new feature were given normal pups to nurse. When they were examined as adult mice, they had cells that glowed red like the mice they had nursed from in their blood, brain, thymus, pancreas, spleen, and kidneys. These cells became functional cells within these organs, so the ones in the brain behaved like neurons and those in the liver made albumin. Based on this experiment, breast milk stem cells travel into the baby’s blood and become functional parts of various organs, at least in mice.

In the laboratory, these stem cells have also shown the ability to differentiate into breast cells that produce milk in a petri dish, as well as bone cells, joint cells, brain cells, heart cells, liver cells, and pancreatic cells that synthesize insulin. In addition, this study may have also discovered a non-invasive, ethical, and sustainable source of multipotent stems.

We don’t yet fully understand the role of these cells in offspring, whether they maintain a tolerance for the mother’s milk, play a role in normal growth and development, or both. Until then, know that your mother is more a part of you than you ever realized.

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The Berlin Patient

February 22, 2015 by

Feb. 27, 2015

By Medical Discovery News

Millions of people around the world are infected with HIV, the virus that causes AIDS, but only one has ever been cured. Known as the “Berlin Patient,” Timothy Ray Brown is a 48-year-old American living in Germany. Scientists and physicians have wondered how he was cured, and some recently published studies in monkeys have provided one clue.

Brown had been HIV positive since 1995. When HIV infects the body’s cells, it integrates its genetic information into cells, making the virus a permanent part of the host’s genetic information. Brown’s HIV was held at bay by antiretroviral drugs that have made this infection survivable.  However, in 2006 he was diagnosed with acute myeloid leukemia (AML), a cancer unrelated to HIV. AML affects a group of blood cells in bone marrow called the myeloid cells. Brown underwent grueling chemotherapy that failed. In the hope of saving his life, he received two bone marrow transplants. The year of his first transplant, he stopped taking the antiretrovirals, which would normally cause a patient’s HIV levels to skyrocket.

Yet, years later, there is no sign of the virus returning. Only traces of HIV’s genetic material have been found in his blood, and those pieces are unable to replicate. The big question now is: how was this accomplished?

His treatment for AML included three different factors that could have individually or collaboratively resulted in curing his HIV infection. First, in preparation for a bone marrow transplant, a patient is treated with a combination of chemotherapy and whole body radiation to eliminate the entire immune system in preparation for receiving a new one. Second, Brown received blood stem cell transplants from a person with a defective cell surface protein, CCR5, which is what HIV uses to enter cells. People with a CCR5 mutation are resistant to HIV infection. Third, his new immune system may have eliminated the virus and remnants of his old immune system that harbored it in something called a graft versus host reaction.

In an experiment to determine how Brown was cured of HIV, scientists isolated blood stem cells from three Rhesus Macaque monkeys and put them into cold storage. They then infected those monkeys as well as three control monkeys with an engineered version of HIV. Soon after infection, all six monkeys were treated with a cocktail of drugs, and just like in humans, the levels of the virus soon declined. A few months later, the first three monkeys underwent radiation treatments to eliminate their immune systems, and then their immune systems were restored using their own stem cells from storage. Months later, the antiretroviral drugs were withheld from all six monkeys, and the virus came roaring back in five of them. One of the monkeys who underwent the stem cell transplant did not have the virus return in its blood, but it was detected in some tissues.

This experiment established that the destruction of immune system prior to bone marrow transplant was not sufficient to eliminate the virus, so the selection of bone marrow cells resistant to HIV infection and/or the graft versus host reaction may be the reason Brown was cured of HIV. Further studies are needed before we will know exactly how HIV can be cured.

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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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