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Cancer, Patient Care, Stem Cells, Transplants

The inside scoop on bone marrow transplants

The inside scoop on bone marrow transplants

blood-156063_1280Your bones harbor blood manufacturing factories. Those factories, packed in the bone marrow, produce stem cells that develop into red blood cells, white blood cells and platelets. Cancers such as leukemia and a few genetic conditions can weaken the bone marrow, necessitating a bone marrow transplant.

Witold Rybka, MD, director of the Bone Marrow Transplantation Program at Penn State Hershey, fielded questions recently in this Q&A on the procedure. An excerpt:

What are the most common types of bone marrow transplants?

For an autologous transplant, the patient can bank his or her own stem cells before undergoing intensive treatment for certain diseases such as lymphoma, Hodgkin’s lymphoma or multiple myeloma. The patient’s body can then use its own banked stem cells to regenerate healthy marrow once treatment is complete. Other transplants are allogeneic, meaning that the patient must receive matching stem cells from a sibling, family member or unrelated donor.

What are the odds of finding a match within one’s own family?

The chance of finding a full match is one in four, so the larger your family, the better chance you have of finding a match among your relatives. Given the size of most American families, most donors must use an unrelated match from a registry of more than 17 million living donors worldwide.

Unfortunately, it’s possible that a patient who needs a bone marrow transfusion won’t get one. Most banked stem cells are from donors in North America and Europe, making it easier for white patients to find a match. For patients of other ethnicities, the chance of finding a donor is only 60 percent, Rybka said.

To learn more about bone marrow transplants, visit Be The Match.

Previously: Bone marrow transplantation: The ultimate exercise in matchmaking, Bone marrow transplantation field mourns passing of pioneer Karl Blume and One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers
Image by OpenClipartVectors

History, Research, Science, Stanford News, Stem Cells

The making of a scientist — Stanford’s Irv Weissman under the Big Sky

The making of a scientist — Stanford's Irv Weissman under the Big Sky

Some people just seem larger than life. That’s certainly the case with stem cell scientist Irving Weissman, MD. His presence fills a room whether he’s speaking to a crowd or conversing one-on-one with a fellow researcher. Some of that presence comes from his academic stature. After all, he’s director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Center for Cancer Stem Cell Research and Medicine. But it’s immediately apparent that Weissman also has a natural ease and composure that’s hard to beat.

Recently, I had the opportunity to shadow Weissman during one of his regular visits to my home state of Montana. Like me, Weissman grew up in Montana and even cut his scientific teeth here at the McLaughlin Research Institute for Biomedical Sciences in Great Falls. My profile of his career is published today in our medical school newspaper, Inside Stanford Medicine.

From the article:

In school, Weissman was a good, but not exceptional, student. He struggled with memorization, and didn’t particularly enjoy reading. His mother was a classically trained pianist, and Weissman played the piccolo and flute.

When he was about 15 years old, a friend of his mentioned a man named Ernst Eichwald, MD, who had been recruited in 1953 from the University of Utah to work as a pathologist at Montana Deaconess Hospital in Great Falls. Eichwald had made the move on the condition that he be allowed to spend part of his time as a one-man research program, studying the biology of skin transplantation in laboratory mice.

“Instead of working at the scrapyard for my father’s hardware store, I went to see Ernst, because my friend said it was fun to be around mice and rats,” Weissman said. “But the difficulty was that he was very hard of hearing, and he spoke in a thick German accent. So I couldn’t understand anything that he was saying, and I was pretty sure he couldn’t understand what I was saying. Finally, in a moment of desperation, I said, ‘I’ll work for nothing!’ Suddenly he understood and could talk to me. So I started to work with him in the summer as mouse caretaker, autopsy assistant and lab researcher.”

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Big data, Cancer, Genetics, Precision health, Research, Stanford News, Stem Cells

Stem-cell knowledge may help outcomes for colon-cancer patients, says Stanford study

Stem-cell knowledge may help outcomes for colon-cancer patients, says Stanford study

Pinpointing which colon cancer patients need chemotherapy in addition to surgery can be difficult. Studies have suggested that those with stage-2 disease aren’t likely to benefit from chemotherapy, so doctors may chose to bypass the treatment and its toxic side effects.

Now cancer biologist Michael Clarke, MD, working with former postdoctoral scholars Piero Dalerba, MD, and Debashis Sahoo, PhD, have found a way to identify a small but significant minority of stage-2 patients who differ from their peers: They have a poorer overall prognosis, but they are also more likely than other stage-2 patients to benefit from additional chemotherapy. The research was published today in the New England Journal of Medicine.

This research is one of the first examples of how we can use our growing knowledge of stem cell biology to improve patient outcomes

From our press release:

Clarke and his colleagues have been studying the connection between stem cells and cancer for several years. For this study, Dalerba and Sahoo sought to devise a way to identify colon cancers that were more stem-cell-like, and thus likely to be more aggressive. They looked for a gene that was expressed in more mature cells but not in stem or progenitor cells. They did this by using a novel bioinformatics approach that drew on their knowledge of stem cell biology to identify developmentally regulated genes important in colon tissue maturation.

Because they knew from previous research by Dalerba in the Clarke laboratory that stem and immature colon cells express a protein called ALCAM, Dalerba and Sahoo looked for genes whose protein product was negatively correlated with ALCAM expression. “We reasoned that those proteins would likely be involved in the maturation of colon tissue and might not be found in more aggressive, immature cancers,” Sahoo said.

Finally, to ensure their results would be useful to doctors, the researchers added another criterion: The gene had to make a protein that was easily detectable by an existing, clinical-grade test.

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Cancer, Immunology, Research, Science, Stanford News, Stem Cells, Transplants

One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers

One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers

4294019174_3f269b3f38_oThe blood stem cell, or hematopoietic stem cell, is a cell that’s believed to give rise to all the components of the blood and immune system. Nestled in our bone marrow, it springs into action as necessary and is a key component of bone marrow transplantation procedures (more accurately called hematopoietic stem cell transplantation) conducted to save patients with blood diseases or whose immune systems have been wiped out by large doses of chemotherapy or radiation.

But new research published today in Stem Cell Reports by research associate Eliver Ghosn, PhD, and colleagues in the laboratory of geneticist Leonore Herzenberg suggests that, at least in laboratory mice, this stem cell may not be as omnipotent as previously thought. In particular, it seems unable to give rise to an important subpopulation of B cells, a type of immune cell. As Ghosn explained to me in an email:

Briefly, our findings challenge the idea that a single blood, or hematopoietic, stem cell (HSC) can fully regenerate all components of the immune system. We’ve shown that transplantation with highly purified HSCs fails to fully regenerate the B lymphocyte compartment, which is needed to protect against infections such as influenza, pneumonia and other infectious diseases, and also to respond to vaccinations.

Further studies conducted by the researchers suggest that these B cells may arise from an alternative fetal progenitor cell distinct from the HSC — perhaps as an evolutionary effort to separate what’s known as innate immunity from adaptive immunity. They urge further research into the clinical outcomes of the transplantation of purified HSC in humans. As Ghosn said:

From a clinical standpoint, these findings raise the key question of whether human HSC transplantation, widely used in human regenerative therapies to restore immunity in immune-compromised patients, is sufficient to regenerate human tissue B cells that help protect transplanted patients from subsequent infectious diseases. This is specially relevant today considering that the field is moving toward using highly purified human HSCs in clinical settings. 
More research is needed to confirm the findings in humans, however. If you’re interested in learning more about this, Ghosn expanded upon the idea earlier this month with a review in the Annals of the New York Academy of Sciences.

Aging, Evolution, Genetics, Research, Science, Stem Cells

The war within: In our aging bodies, the “fittest” stem cells may not be the ones that ensure our survival

The war within: In our aging bodies, the "fittest" stem cells may not be the ones that ensure our survival

ageAnti-aging research has been in the news lately: for instance, here, here and (less recently and less frivolously) here.

Albert Einstein College of Medicine researcher Nir Barzilai, MD, who’s spearheading the groundbreaking anti-aging trials referred to in these articles, is far from frivolous. I remember really liking a talk he gave at Stanford a few years ago about his ongoing study of super-old Ashkenazis, at a symposium sponsored by Stanford’s Glenn Laboratories for the Biology of Aging.

Now, Tom Rando, MD, PhD, the director of Glenn Labs at Stanford, has co-authored a thought-provoking review in Science that advances a theory of why we age.

It’s not the only theory. Judy Campisi of the Buck Institute for Research on Aging, for example, has explored the detrimental activities of differentiated cells gone wrong within our tissues. The older the tissue, the wronger the cells in it go.

Rando and his co-author, Baylor College of Medicine regenerative-medicine expert Margaret Goodell, PhD, come at aging from the opposite end of the spectrum: stem cells, the least-differentiated cells in the body. In particular, Rando and Goodell target the aging-associated actions of so-called somatic stem cells, which reside in virtually all (and, probably, actually all) of our tissues and whose fates are restricted to spawning only cell types that belong in those tissues. While we’re growing up, those somatic stem cells are the reason why: They divide to generate the differentiated cells that bulk us up. Once we’ve matured, they mostly hang back, springing into action to replace tissue lost to injury or to wear and tear.

Radiation, noxious foreign substances, and plain old existence wreaks sporadic damage on somatic stem cells by triggering genetic mutations or by altering the cells’ epigenetic settings, the patterns of chemical stop-and-go signs that variously switch the 20,000-odd genes in each cell’s genome on or off. These insults pile up as life’s pages turn. Eventually, Rando and Goodell write, a curious, Darwin-like natural selection occurs among our tissue-resident stem cells.

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Evolution, Fertility, Pregnancy, Research, Science, Stanford News, Stem Cells, Videos

Viral RNA essential for human development, say Stanford researchers

Viral RNA essential for human development, say Stanford researchers

Viruses are tricky, but we humans may be trickier still. Stanford stem cell biologists Vittorio Sebastiano, PhD, and Jens Durruthy-Durruthy, PhD, published a study today in Nature Genetics indicating that the genetic remnants of ancient viral infections that still linger in our genome are essential to early human embryonic development.

As Sebastiano explained in our release:

We’re starting to accumulate evidence that these viral sequences, which originally may have threatened the survival of our species, were co-opted by our genomes for their own benefit. In this manner, they may even have contributed species-specific characteristics and fundamental cell processes, even in humans.

The researchers, who talk about their work in the video above, relied on a new RNA sequencing technique to investigate the expression of what are called long-intergenic noncoding, or lincRNAs. These molecules don’t contain protein-making instructions, but instead affect the expression of other genes. They’ve been implicated in many important biological processes, including the acquisition of a developmental state called pluripotency that is necessary for a fertilized egg to develop into the cells and tissues of a growing fetus.

More from our release:

They identified more than 2,000 previously unknown RNA sequences, and found that 146 are specifically expressed in embryonic stem cells. They homed in on the 23 most highly expressed sequences, which they termed HPAT1-23, for further study. Thirteen of these, they found, were made up almost entirely of genetic material left behind after an eons-ago infection by a virus called HERV-H.

[…] After identifying HPAT1-23 in embryonic stem cells, Sebastiano and his colleagues studied their expression in human blastocysts — the hollow clump of cells that arises from the egg in the first days after fertilization. They found that HPAT2, HPAT3 and HPAT5 were expressed only in the inner cell mass of the blastocyst, which becomes the developing fetus. Blocking their expression in one cell of a two-celled embryo stopped the affected cell from contributing to the embryo’s inner cell mass. Further studies showed that the expression of the three genes is also required for efficient reprogramming of adult cells into induced pluripotent stem cells.

I can’t stop marveling at the close ties we have with viruses. It makes me think of the words of Michael Corleone in The Godfather: “Keep your friends close, and your enemies closer.” As Durruthy-Durruthy told me, “It’s fascinating to imagine how, during the course of evolution, primates began to recycle these viral leftovers into something that’s beneficial and necessary to our development.”

Previously: My baby, my… virus? Stanford researchers find viral proteins in human embryonic cellsMastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled  and Species-specific differences among placentas due to long-ago viral infection, say Stanford researchers
Video by Christopher Vaughan/Stanford Institute for Stem Cell Biology and Regenerative Medicine

Ethics, In the News, NIH, Research, Science, Science Policy, Stanford News, Stem Cells

Stanford researchers protest NIH funding restrictions

penSeven Stanford researchers, including Irving Weissman, MD, who directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, and David Magnus, PhD, director of Stanford’s Center for Biomedical Ethics, have joined with four other prominent scientists to urge the lifting of a recent and unexpected ban on funding by the National Institutes of Health for research that involves placing human stem cells into early-stage, non-human embryos. Their comments will be published tomorrow in a letter to Science.

As I describe in our release:

At issue is the growing field of research that seeks to understand how human pluripotent stem cells, which can become any cell type, may integrate and contribute to the development of a nonhuman animal, such as a laboratory mouse. Pluripotent stem cells can be isolated from human embryos or created in a lab from adult human cells, in which case they’re known as induced pluripotent stem cells. Once obtained, these versatile cells can be injected into an early-stage animal embryo and studied as the embryo develops into an adult animal.

Tracking where these cells go and how they function in the growing embryo and the adult animal can help researchers understand early stages of human development that can’t be studied any other way. (Although researchers can and do study the development of fertilized human eggs, the study period is restricted to only a few days after fertilization for ethical reasons.)

In addition to investigating human development, the research is expected to lead to significant advances in disease modeling, drug testing and even transplantation. As cardiologist and one of the co-senior authors of the letter, Sean Wu, MD, PhD, explains:

By eliminating federal funding for all aspects of this research, the NIH casts a shadow of negativity toward all experiments involving chimera studies regardless of whether human cells are involved. The current NIH restriction serves as a significant impediment to major scientific progress in the fields of stem cell and developmental biology and regenerative medicine and should be lifted as soon as possible.

Science recently published a great background article describing the ban, and its effect on researchers like Sean Wu and geneticist and stem cell researcher Hiromitsu Nakauchi, MD, PhD, who also signed the letter. Other signees include Joseph Wu, MD, PhD, professor of medicine and director of Stanford Cardiovascular Institute; Christopher Scott, PhD, director of Stanford’s Program on Stem Cells and Society; and Vittorio Sebastiano, PhD, assistant professor of obstetrics and gynecology and director of Stanford’s Human Pluripotent Stem Cells Core Facility.

Previously: NIH intramural human embryonic stem cell research haltedSupreme Court decision on human embryonic stem cell case ends research uncertaintyUsing organic chemistry to decipher embryogenesis and The best toxicology lab: a mouse with a human liver
Photo by Fimb

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

Events, Neuroscience, Science, Stanford News, Stem Cells

Stanford Neuroscience Institute’s annual symposium captured on Storify

Stanford Neuroscience Institute's annual symposium captured on Storify

IMG_0246When I talked to William Newsome, MD, PhD, director of the Stanford Neurosciences Institute, about its annual symposium last week, he told me one of the pleasures of directing the institute is getting to pick speakers whose science he really likes.

We captured tweets, images and videos from those speakers on our Storify page, and they make it clear that Newsome has very diverse tastes. Topics ranged from aging and mental health policy to virtual reality for mice.

From Stanford, geneticist Anne Brunet, PhD, discussed her work on aging, particularly how stem cells in the brain change with age. Engineer Krishna Shenoy, PhD, described how his lab was reading signals from the brains of paralyzed people and using those to drive computer cursors or prosthetic limbs. Others discussed machine learning, new technologies for imaging the brain, the genetics of mental health disorders, and insights into how smells illicit behaviors in flies.

It’s worth a look at the Storify page to get a sense of the breadth of work encompassed under the banner of neuroscience.

Previously: “Are we there yet?” Exploring the promise, and the hype, of longevity researchMy funny Valentine – or, how a tiny fish will change the world of aging research and Stanford researchers provide insights into how human neurons control muscle movement
Photo of Krishna Shenoy by Matt Beardsley

Cardiovascular Medicine, Research, Stanford News, Stem Cells

Tension helps heart cells develop normally, Stanford study shows

Tension helps heart cells develop normally, Stanford study shows

heart_newsTension might not be fun for us, but it looks like it’s critical for our hearts. So much so that without a little tension heart cells in the lab fail to develop normally.

This is a finding that took a mechanical engineer looking at a biological problem to solve. For many years now scientists have been able to mature stem cells into beating clumps of cells in the lab. But although those cells could beat, they didn’t do it very well. They don’t produce much force, can’t maintain a steady rhythm and would be a failure at pumping actual blood.

Beth Pruitt, PhD, a Stanford mechanical engineer, realized that in our bodies heart cells are under considerable tension, and thought that might be critical to how the cells develop.

She and postdoctoral scholar Alexandre Ribeiro started investigating how heart cells matured in different shapes and under different amounts of tension. They found a combination that produces normal looking cells with strong contractions.
The work could be useful for scientists hoping to replace animal heart cells as the gold standard for identifying heart-related side effects of drugs. Those cells are quite different from our own and often fail to detect side effects that could damage hearts in people taking the drug.

In my story about the work, I quote Ribeiro saying, “We hope this can be a drop-in replacement for animal cells, and potentially instead of having to do individual recordings from each cell we could use video analysis.”

Previously: A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells and “Clinical trial in a dish” may make common medicines safer, say Stanford scientists
Photo by Alexandre Ribeiro

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