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Cancer, Research, Sleep, Stanford News, Stem Cells, Transplants

Sleep deprivation affects stem cell function, say Stanford scientists

Sleep deprivation affects stem cell function, say Stanford scientists

sleepy mouseWe all know that sleep is important for many biological functions. But I’m still surprised at the breadth of its influence. Today, a former postdoctoral scholar at Stanford, Asya Rolls, PhD, published a fascinating study in Nature Communications showing that blood-forming stem cells from drowsy mice perform more poorly when transplanted into recipient animals. In particular, they are less able to home to the bone marrow, and they generate a smaller proportion of a type of immune cell called a myeloid cell than do stem cells from well-rested mice.

Although the researchers studied only laboratory mice, the possible implications for human transplant recipients (in humans, these procedures are called hematopoietic stem cell transplants, or sometimes bone marrow transplants) are intriguing. As Rolls, who is now an assistant professor at the Israel Institute of Technology, said in our release, “Considering how little attention we typically pay to sleep in the hospital setting, this finding is troubling. We go to all this trouble to find a matching donor, but this research suggests that if the donor is not well-rested it can impact the outcome of the transplantation.”

At Stanford, Rolls worked in the laboratory of psychiatrist and sleep medicine specialist Luis de Lecea, PhD, and she collaborated with Wendy Pang, MD, PhD, and Irving Weissman, MD, director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, to conduct the research.

Despite the fact that sleep deprivation in the donor reduced the efficacy of their stem cells by about 50 percent, all is not lost. From our release:

Although the effect of sleep deprivation was stark in this study, Rolls and her colleagues found that it could be reversed by letting the drowsy mice catch up on their ZZZs. Even just two hours of recovery sleep restored the ability of the animals’ stem cells to function normally in the transplantation tests.

“Everyone has these stem cells, and they continuously replenish our blood and immune system,” said Rolls. “We still don’t know how sleep deprivation affects us all, not just bone marrow donors. The fact that recovery sleep is so helpful only emphasizes how important it is to pay attention to sleep.”

Previously: In mice, at least, uninterrupted sleep is critical for memory and Bone marrow transplantation: The ultimate exercise in matchmaking
Photo by Eddy Van 3000

Immunology, Infectious Disease, Precision health, Research, Stanford News, Transplants

A blood test that monitors for post-lung-transplant rejection and infection

A blood test that monitors for post-lung-transplant rejection and infection

lungsA team under the direction of Stanford bioengineer Steve Quake, PhD, has shown that a noninvasive blood test can accurately diagnose lung-transplant rejection. The test also simultaneously detects infections by patient-imperiling microbes.

About 3,500 lung transplant procedures are performed annually worldwide. But median survival after the graft barely exceeds five years, trailing the outcomes for kidney, heart, liver and other solid organ transplants. Chronic organ rejection is the biggest single factor. Infection (for which recipients are at high risk due, ironically, to their post-transplant regimen of immune-suppressing drugs given to reduce the likelihood of organ rejection) is another leading contributor.

In a study published in Proceedings of the National Academy of Sciences, Quake and his associates demonstrated that the test, which involves high-throughput sequencing of DNA, flags organ rejection by detecting increasing amounts of donor DNA in a recipient’s blood. The relatively low-cost test doesn’t require the highly invasive removal of lung tissue, and it can also screen for myriad bacterial, viral and fungal pathogens.

In another study in 2014, Quake and Stanford colleagues had come up with a similar blood test to determine whether a heart-transplant recipient was headed for organ rejection. The new study expands the test’s applicability to lung transplantation – and suggests that its utility may extend to solid organs in general, including more-frequently performed procedures such as kidney transplantation (more than 17,000 in the United States alone in 2014).

With better than half of all lung-transplant patients suffering organ rejection in just the first year after their operation, this advance holds great clinical potential. Quick, accurate diagnosis is the first step toward appropriate treatment.

Previously: A simple blood test may unearth the earliest signs of heart transplant rejection, Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health and Might kidney-transplant recipients be able to toss their pills?
Photo by Lorraine Santana

Cancer, Patient Care, Stanford News, Transplants, Videos

Immunosuppression brings higher risk for skin cancer – and need for specialized care

Immunosuppression brings higher risk for skin cancer – and need for specialized care

An estimated 50 million Americans must take immunosuppressants to treat more than 80 autoimmune disorders, according to the National Institutes of Health. These medications are particularly vital to the survival of people who have undergone organ transplants to prevent their bodies from rejecting their donor organ.

While immunosuppressants can be life-saving, their very action of reducing the body’s innate defense systems can have negative side-effects. One particularly dangerous concern is an increased risk for skin cancer, particularly for those individuals with fair skin or an inherited tendency to develop skin cancers. (My colleague Tracie White told the story of one transplant patient’s struggle here earlier this summer.)

To address the specialized needs of patients taking immunosuppressants or with compromised immune function, Stanford dermatologists recently launched the High-Risk Skin Cancer Clinic.

In this Stanford Health Care video, the clinic’s Carolyn Lee, MD, PhD, explains the particular vulnerabilities of transplant patients to aggressive skin cancer and the importance of a dedicated clinic to meet their needs. “What we hate to see — and it’s easily preventable — is someone who’s been waiting for a transplant to finally get it, only to be felled by skin cancer,” she says.


Previously: Rebuilding Cassie’s smile: A lung transplant patient’s struggle with skin cancer and This summer’s Stanford Medicine magazine shows some skin

Genetics, Pediatrics, Transplants, Women's Health

Rare African genes might reduce risks to pregnant women and their infants

Rare African genes might reduce risks to pregnant women and their infants

Khoe-SanWhen Hugo Hilton began working at Stanford as a young researcher several years ago, his supervisor set him to work on a minor problem so he could practice some standard lab techniques. His results, however, were anything but standard. His supervisor — senior research scientist Paul Norman — told him to do the work over, convinced the new guy had made a mistake. But Hilton, got the same result the second time, so Norman made him do it over again. And then again.

“This was Hugo’s first PCR reaction in our lab and I gave him the DNA,” recalled Norman, “and the very first one he did, he pulled out this mutation. I was convinced that he’d made a mistake.” Norman even quietly redid the work himself. But the gene variant was real.

Norman and colleagues had been studying the same group of immune genes for decades and he knew them like the back of his hand. Yet he was astonished by what Hilton had stumbled on — a mutation that switched a molecular receptor from one protein target to another. It would be as if you bent your house key ever so slightly and discovered it now opened the door to your neighbor’s apartment — but not yours.

And the mutation, far from causing some illness, might contribute to healthier mothers and babies. Parallel research at another institution suggests the odd gene most likely changes the placenta during early pregnancy, leading to better-nourished babies and a reduced risk of pre-eclampsia, a major cause of maternal death.

The surprising finding grew out of a long-term effort to understand how immune system genes make us reject organ transplants. A big part of that puzzle is understanding how much immune genes can vary. On the surfaces of ordinary cells are proteins called HLAs. Combinations of these proteins mark cells in a way that makes each person’s cells so nearly unique that the immune system can recognize cells as either self or not self. When a surgeon transplants a kidney, the recipient’s immune system can tell that the kidney is someone else’s — just from its cell surface HLA proteins. The patient’s immune system then signals its natural killer cells to attack the transplanted kidney. The key to all that specificity is the huge variation in the genes for the HLA proteins.

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Cancer, Chronic Disease, Dermatology, Stanford News, Surgery, Transplants

Rebuilding Cassie’s smile: A lung transplant patient’s struggle with skin cancer

lung patientWhen I first met Cassie Stockton, she was seated in an exam chair in Stanford’s dermatology clinic, getting cosmetic skin treatments. Lovely and young, just 21 years old, it seemed a bit silly. How could she possibly need injectable lip fillers or laser skin treatments?

I knew Stockton had a lung transplant at 15 and that the immunosuppressant drugs she was required to take to keep her body from rejecting the donated lungs had made her susceptible to skin cancer. But it wasn’t until I researched her story in depth that I truly understood how she ended up needing regular cosmetic treatments here.

As I explain in my recently published Stanford Medicine article, her story began at birth:

Born premature, [Cassie] was intubated the first two weeks of life, then sent home with her mother and an oxygen tank. She remained on oxygen 24 hours a day for the first two years of her life. Eventually, she was diagnosed with bronchopulmonary dysplasia, a chronic lung disorder …

Sixteen years later, the donated gift of new lungs saved her life – but it left scars, both emotional and physical:

The day Stockton woke up out of the anesthesia six years ago after a 13-hour surgery at the Transplant Center at Lucile Packard Children’s Hospital Stanford, she breathed in oxygen with newly transplanted lungs, and breathed out sobs. Tears streamed down her face. “At first, I thought she was in pain,” says her mother, Jennifer Scott, who stood by her side. But that wasn’t it. Stockton was overwhelmingly sad because she now knew her new lungs were the gift of a child. It was Dec. 6, 2009, just before Christmas. The death of someone else’s child had given her a whole new life.

And now:

Every four months, she and her fiancé make the four-hour drive from their home in Bakersfield, California, past the oil rigs and cattle farms to Stanford’s Redwood City-based dermatology clinic for her skin cancer screening. It’s been two years of treatments: freezings, laserings, a total of eight outpatient skin surgeries — the most significant resulting in the removal of the left half of her lower lip. The dermatologic surgeon removes the skin cancers, and then gets to work to repair the damage. “It’s heart-breaking to have to remove the lip of a 21-year-old woman,” says Tyler Hollmig, MD, clinical assistant professor of dermatology and director of the Stanford Laser and Aesthetic Dermatology Clinic, who leads Stockton’s treatment and keeps her looking like the young woman she is, restoring her skin, rebuilding her lip, making sure she keeps her smile.

Stockton doesn’t complain about any of the struggles she’s had post transplant. She knows she got a second chance at life. And, she tells me, it’s her job to take care of the lungs given to her by that child who died.

Previously: This summer’s Stanford Medicine magazine shows some skin
Photo by Max Aguilera-Hellweg

Cardiovascular Medicine, Chronic Disease, In the News, Research, Stanford News, Transplants

Are donor hearts getting wasted?

Are donor hearts getting wasted?

heart choiceI wrote a press release recently on a study that showed a high percentage of donated hearts were not being used, raising concerns that some were getting wasted when they could be used to save lives. This made me curious about the process of just how a donor heart, which ideally has about a two-hour window before it gets transplanted to a patient with heart failure, gets matched.

The result is a Stanford Medicine magazine story titled “Heart Choices” that describes this process, the tough decisions that family members make when a loved one donates a heart, and the excruciating waiting that patients in need of a new heart go through.

Most importantly the article asks the question: Should more “high-risk” donor hearts be used? An estimated 20,000 people across the country are waiting for new hearts, and only a few thousand transplants happen on average per year. My story explains the dilemma:

The general assumption is that there simply are not enough donor hearts available to meet a growing demand. But new research is questioning that assumption. Some researchers and surgeons claim that thousands of donor hearts that could be used are turned away each year. The hearts are considered marginal because they come from older, sicker or riskier donors, but many argue they are safe for transplant, and could be saving lives.

“As patients wait longer, they often get sicker, and we often lose patients,” says Stanford cardiologist Kiran Khush, MD, whose research reports that 65 percent of available heart donations are discarded because of stringent acceptance criteria. Yet the criteria have not been critically evaluated, she says. “Increasing the supply of donor hearts is, of course, a great concern of mine.”

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History, Patient Care, Stanford News, Transplants

A look back at one of Stanford’s first kidney donors

A look back at one of Stanford's first kidney donors

Inga GoodnightMuch of medical science writing involves reporting on the next potentially lifesaving treatment. But sometimes it’s rewarding to look back. The recent death of one of Stanford’s first kidney donors had me doing just that – and exploring a time when this now-common procedure was cutting edge.

Inga Goodnight, who died at the age of 99 in April, donated her kidney to her son Gary, who went on to live another 37 years.

As I wrote in a just-published article on their story:

Today, kidney transplants are established procedures; more than 17,000 were performed in the United States last year. Improvements in surgery and immunosuppressive drugs have increased the number of potential kidney matches. Studies have shown that donors have no increased health risks compared with the general public.

But in 1965, when Gary became the third patient to receive a kidney transplant at Stanford, many things were unknown. Doctors were still determining proper dosages for the immunosuppressive drugs, and they didn’t know if Gary’s body would reject the kidney or if he would even survive the first year.

While it was known that a person could live with one kidney, no one knew if there would be long-term health impacts for Inga. And unlike modern laparoscopic surgery, with its tiny incisions and short hospital stays, the surgery to remove the Inga’s kidney involved a large incision that cut through abdominal muscles and required a long recovery.

While these advancements in medicine were interesting, I found my conversation with Bill Goodnight (Inga’s son and Gary’s brother) about his memories from this time equally informative. In many ways their attitudes towards Gary’s condition and treatment seemed quite modern.

Gary Goodnight was aware that his kidneys weren’t going to last and actively followed the news about the emerging field of transplants. Both Bill and his mother had themselves tested to see which might make a good match. And, similar to today’s patients and families with life threatening conditions, the Goodnight family approached the procedure with hope.

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: Double kidney transplants leave Hawaii siblings raring to goKidney-transplant recipients party without drugs – immune suppressing anti-rejection drugs, that is and Well blog: Minnesota man denied insurance for donating kidney
Photo courtesy of Bill Goodnight

Precision health, Research, Science, Transplants

Study: Treatment plans for kidney failure should consider cause and circumstances of disease

Study: Treatment plans for kidney failure should consider cause and circumstances of disease

3349943474_0e1bc4236b_zOne size seldom fits all, so it’s not surprising that one treatment regimen may not suit all patients with the same condition. Now, a new study of end-stage kidney failure shows the importance of taking factors like cause and circumstances of a patient’s disease into account when designing a treatment plan.

The study (subscription required) began when Stanford nephrology fellow Michelle O’Shaughnessy, MD, noted that patients with end-stage kidney-failure usually received the same generic treatment plan (dialysis or a kidney transplant), even though there are different causes of the disease and a patient’s condition can progress to kidney failure via many different routes.

As described in our press release, kidney disease is often caused by diabetes or hypertension, but it can also be caused by glomerular disease, a condition with many distinct subtypes. And:

[E]ach of the many glomerular disease subtypes is unique. In certain subtypes, the immune system attacks the kidneys; in others, it damages the blood vessels.

As a result, the various subtypes are treated using different methods before the kidneys begin to fail. The treatments may include steroids or stronger immunosuppressant medications. The resulting side effects can range from severe infections to diabetes to cancer.

For their work, O’Shaughnessy and her colleagues examined data collected from 84,301 patients with end-stage kidney disease caused by one of six major subtypes of glomerular disease. The results showed that the type of glomerular disease significantly affected how long the patient lived after they developed kidney failure; mortality ranged from 4 percent per year for one type of patient to 16 percent per year for another.

“It’s important to know why one kidney patient does well and another does poorly,” concluded O’Shaughnessy. “If physicians take into consideration what caused the kidneys to fail in the first place and what types of treatments patients received prior to kidney failure, it could possibly improve the patients’ quality of life or increase their life span.”

Previously: Keeping kidney failure patients out of the hospitalStudy shows higher Medicaid coverage leads to lower kidney failure ratesStudy shows higher rates of untreated kidney failure among older adults and Geography may determine kidney failure treatment level
Photo by scribbletaylor

Cancer, Dermatology, Infectious Disease, Stanford News, Transplants

This summer’s Stanford Medicine magazine shows some skin

This summer's Stanford Medicine magazine shows some skin

below surface banner and 1 blogSkin is superficial, literally. But it’s also really deep, as I realized while editing the just-published issue of Stanford Medicine magazine. The summer issue features the special report “Skin deep: The science of the body’s surface.”

I learned from the chair of Stanford’s Department of Dermatology, Paul Khavari, MD, PhD, that thousands of diseases affect the skin. And I learned it’s surprisingly abundant: An average-sized adult is covered with about 20 square feet of skin.

Research on skin is thriving, in part, because skin is so easy to get hold of, Khavari told me. “The accessibility of skin tissue to the application of new technologies, including genomics, proteomics, and metabolomics, make this a watershed moment for progress in alleviating the tremendous suffering caused by the global burden of skin disease,” he said.

The magazine, produced with support from the dermatology department, includes articles not only about new treatments, but also insights into how skin works when it’s healthy and how to keep it that way. In a Q&A and audio interview, actress and playwright Anna Deavere Smith, who is African-American, addresses skin’s social meaning, discussing her relationship to her own skin and how, as a writer and actor, she gets under the skin of her characters. The online version of the magazine includes audio of an interview with Smith.

Also in the issue:

  • The butterfly effect“: A story about two young men coping with one of the world’s most painful diseases — the skin-blistering condition epidermolysis bullosa — including news about an experimental treatment to replace their broken genes. The online version includes a video with a patient at home and interviews with experts on the condition.
  • Surviving melanoma“: A report on progress being made after years of stagnation in treating the most deadly skin cancer: melanoma.
  • The rarest of rashes“:  A look at one of Stanford Medicine’s great accomplishments in dermatology: successful treatment of a rare but dangerous rash — cutaneous lymphoma, a form of blood cancer that spreads to the skin.
  • Take cover“: Tips on keeping skin safe from the sun.
  • Wither youth“: A feature on research seeking to answer the question: Why does skin age?
  • New lungs, new life“: The story of a young woman who lost her smile and had it restored through surgery.

The issue also includes a story considering the rise in number of castoff donor hearts, despite a shortage of the organs for transplants, and an excerpt from Jonas Salk: A Life, a new biography of the polio-vaccine pioneer, written by retired Stanford professor Charlotte Jacobs, MD.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Stanford Medicine magazine traverses the immune system and Stanford Medicine magazine opens up the world of surgery
Photo, from the Summer 2015 issue of Stanford Medicine, by Max Aguilera-Hellweg

Applied Biotechnology, In the News, Research, Stem Cells, Transplants

“Supplying each cell with a scuba tank”: New advances in tissue engineering

"Supplying each cell with a scuba tank": New advances in tissue engineering

membrane-article.jpgResearchers in the U.K. have found a way to make growing synthetic tissue more sustainable. At present, the size of engineered tissues is limited because the cells die from lack of oxygen when the pieces get too big. By adding an oxygen-carrying protein to the stem cells prior to combining them with tissue scaffolding, the researchers overcame this problem.

The study, led by Adam Perriman, PhD, research fellow at the University of Bristol’s Synthetic Biology Research Centre, and Anthony Hollander, PhD, professor of integrative biology at the University of Liverpool, was published yesterday in Nature Communications. The tissue they were fabricating was cartilage, but the process could potentially be applied to other tissues, as well.

Perriman describes the findings in a press release:

We were surprised and delighted to discover that we could deliver the necessary quantity [of oxygen] to the cells to supplement their oxygen requirements. It’s like supplying each cell with its own scuba tank, which it can use to breathe from when there is not enough oxygen in the local environment.

Hollander also comments on the significance of the research:

We have already shown that stem cells can help create parts of the body that can be successfully transplanted into patients, but we have now found a way of making their success even better. Growing large organs remains a huge challenge but with this technology we have overcome one of the major hurdles.

Creating larger pieces of cartilage gives us a possible way of repairing some of the worst damage to human joint tissue, such as the debilitating changes seen in hip or knee osteoarthritis or the severe injuries caused by major trauma, for example in road traffic accidents or war injuries.

Previously: Building bodies, one organ at a time, How Stanford researchers are engineering materials that mimic those found in our own bodies and A brief look at “caring” for engineered tissue
Photo by Warwick Bromley

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