Category Archives: stem cells

Blood on the lab bench

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Scientists in Qatar have taken research into organ development one more step into the future by expanding the potential for creating personalized blood and heart tissue in the lab.

The scientists, under the lead of Arash Rafii Tabrizi at Weill Cornell Medicine – Qatar, have postulated that endothelial cells, which line the walls of blood vessels, are a vehicle for organ development. “Different organs have different endothelial cells that express different and specific factors called angiocrine factors that lead to the development and function of the organ,” explains Tabrizi.

In order to test this, the scientists forced the expression of said transcription vectors in the lab. Twenty days later, the cells multiplied and differentiated into the building blocks of blood cells: hematopietic stem cells. These are the basis for cells such as red and white blood cells and platelets.

“If you have leukemia, for example, we would retrieve your endothelial cells and we could transform that into blood. It would be an unlimited personal source of blood for each individual,” says Tabrizi.

In addition to blood, the researchers paired endothelial cells with heart muscle cells to create more muscle cells, that beat together rhythmically, in a petri dish.

The scientists maintain, however, that it’s too early to make any sweeping assumptions about the reliability of results, not until the tests move into the animal and human trial phases.

Read more about what the scientists have termed a breakthrough discovery here.

 

March issue cover: What’s going on here?

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March

Alamy photo “Talus cones on Svalbard”

March is already winding to a close, but we wanted to take a quick break to answer that most burning of all questions: what is going on with our cover this month?

On p.331 of this month’s issue, Owen Rackham and colleagues describe an algorithm called Mogrify that predicts transcription factor combinations for direct reprogramming between 173 human cell types and 134 tissues (see also the News and Views by Patrick Cahan).

Mogrify effectively paints a landscape of cell conversions and provides directions for getting from one point to another. This is often visualized using a variation on Waddington’s epigenetic landscape (for example, see “A deterministic map of Waddington’s epigenetic landscape for cell fate specification” by Bhattacharya et al.).

Visualization of Waddington's epigenetic landscape

Visualization of Waddington’s epigenetic landscape{credit}Bhattacharya et al. BMC Syst Biol. 2011; 5: 85.{/credit}

The epigentic landscape as imagined by Waddington involves a marble (the cell) rolling down a hill with many alternate paths (cell fates).

You can imagine the image on the cover (depicting talus deposits on the surface of a mountain in Norway) as the epigenetic landscape, with the different cell fates rising out of the pluripotent state. In this case, there is no marble, because the cell and its fate (address on the landscape) are in fact the same thing. But similar to the talus cones, the cell’s fate is not unchangeable. As Mogrify makes clear, the cell has the potential to transform into many different cell types, regardless of its current address on the landscape. We just have to understand the map to help it get there.

Other articles related to Mogrify:

Breakthrough in human cell transformation could revolutionise regenerative medicine (University of Bristol press release)

Serendipity’s touch on cell conversions (Duke-NUS)

Are you talking to me?

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Melissa JonesIntroducing Melissa Jones, one of the London Naturejobs Career Expo journalism competition runners-up.

I am an alumna of California State University Long Beach and a PhD candidate in Biomedical Sciences and Translational Medicine at Cedars-Sinai Medical Center in Los Angeles, California. My scientific interests include molecular mechanisms of human diseases, stem cell biology, and vision research. As a Southern California native, I enjoy going to the beach, running, and reading. My favourite book is Jurassic Park by Michael Crichton, because I like the moral that scientists should think about the consequences of their research in addition to the technicality of the experiments.

—-x—-

I am the only person in my family not pursuing a career in business. While they discuss market strategies, I am busy trying to figure out why I’ve been stuck on this antibody that hasn’t worked for the last four years (A little help, Santa Cruz Biotech?).

But my family and I aren’t worlds apart in the way we think, it’s just the jargon that we use. Science can be considered as a business, whether a biotech company or in academia. Scientists try to sell their ideas to grant review committees, a class of undergraduate students or to a group of donors. An important aspect of it is how well you are able to pitch your idea in a clear and productive manner, a task that many people often forget and a trait that is hard to teach. Continue reading →

Highlights from the Keystone Symposium on Stem Cells & Reprogramming

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View from the Resort at Squaw Creek. Not a bad place for a conference!

View from the Resort at Squaw Creek. Not a bad place for a conference!{credit}Brooke LaFlamme{/credit}

I recently attended the joint Keystone Symposium “Stem Cells & Reprogramming” and “Engineering Cell Fate & Function” at the beautiful Resort at Squaw Creek. In addition to gorgeous weather, there was an amazing lineup of talks demonstrating the power and promise of stem cells and cell/tissue engineering. Here are just a few of the highlights from the meetings:

Keynote: Optogenetics

Karl Deisseroth from Stanford University kicked off the joint meeting with an overview of his lab’s research in optogenetics and how they’ve used the technology both to control and map neuronal networks in live animals or intact tissues. The Deisseroth lab has used optogenetics to better understand the neuronal architecture and genetic structure underlying complex behaviors, such as those associated with anxiety. In his talk, Prof. Deisseroth outlined how they are using optogenetic tools to target neuronal wiring using Boolean-like genetic systems to identify neurons expressing specific combinations of markers.

The second part of his talk focused on CLARITY, a method developed in the Deisseroth lab to allow for 3D imaging of neurons in intact tissues or whole brains. You can see some of the amazing videos generated with this technique here.

To learn more, you can find a list of Deisseroth lab publications here.

Stem cells and reprogramming in human disease modeling and treatment

There were a ton of talks (and posters) demonstrating the utility of stem cells and directed differentiation for human disease modeling and treatment development. I’ll only mention a few here, but all the talks were excellent. Continue reading →

California governor vetoes egg-payment law

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California Governor Jerry Brown has vetoed a proposed law that would have allowed payments to women who give their eggs to scientific researchers, a move that may deter other states from attempting to ease similar bans.

The measure gained attention in May after an Oregon researcher, Shoukhrat Mitalipov, published a paper showing that he could derive stem cell lines from cloned human embryos. Mitalipov paid the women who donated the eggs US$3,000–7,000 apiece, removing a significant bottleneck in the cloning process: the availability of human eggs, which must be harvested in a time-consuming and uncomfortable procedure.

In his veto message on 13 August, Brown cited ethical concerns: “Not everything in life is for sale nor should it be,” Brown wrote. The American Society for Reproductive Medicine in Birmingham, Alabama, co-sponsored the proposed law. A coalition of conservative and watchdog groups opposed it and lauded the veto.

“It would be unconscionable to expand the commercial market in women’s eggs without obtaining significantly more information about the risks of retrieving them,” said Diane Tober, associate executive director at the Center for Genetics and Society in Oakland, California, in a statement.

Even if Brown had signed the proposed law, separate rules still prohibit the state’s California Institute for Regenerative Medicine from funding research on stem cell lines created with eggs from paid donors. The agency’s leadership has asked for an amendment of those rules, but that move is stalled for now.

 

Stem cells may be too young to accurately model age-related brain disorders

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JosephJoseph Jebelli is a Neuroscience PhD Candidate at University College London (UCL). His research involves studying the cellular and molecular mechanisms of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease.

New research suggests that human embryonic stem cells, which are experimentally manipulated to develop into mature neurons to model brain diseases, may in fact more closely represent foetal brain cells than those seen in the ageing brains of disease sufferers.

Over the past 20 years, scientists have been exploring the potential of stem cells to provide therapeutic intervention in a variety of brain disorders, such as Alzheimer’s disease, Parkinson’s, and stroke.

The aims are twofold: 1. to harness them as a cellular transplantation therapy, effectively replacing the cells lost in disease, and 2. to generate particular types of neurons in isolation, and to examine what causes them to die in the brain in the first place. At present, the latter is a more realistic goal. Continue reading →

First vein grown from human stem cells successfully transplanted into a young girl

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First came bladders. Then pulmonary arteries. Followed by urethras, arteriovenous shunts and tracheas. Now, in another first for the world of tissue-engineered body parts, Swedish surgeons have successfully transplanted a bioengineered vein into a 10-year-old girl suffering from portal vein obstruction.

“This is a very good start for demonstrating what impact regenerative medicine can have on patients by using a biological matrix and seeding it with a patient’s own cells,” says Juliana Blum, cofounder and senior director of business operations at Humacyte, a North Carolina–based company developing bioengineered blood vessels for dialysis patients.

A team led by Suchitra Sumitran-Holgersson at the University of Gothenburg took a 9 centimeter-long snippet of vein from the groin of a deceased donor, stripped it of all cells and then reseeded the resulting hollow tube with stem cells taken from the recipient’s own bone marrow. Two weeks later, the surgeons transplanted the engineered conduit into the young girl. She remained healthy for close to a year, although a second procedure was then needed to lengthen the first graft after the vein started to constrict. Ever since the second transplant, in February of this year, the girl’s energy levels have improved and the blood flow to her kidneys are back to normal.

“The girl is somersaulting now,” says Sumitran-Holgersson, who reported the findings today in The Lancet. “Her parents told me, ‘We have a completely different child.’”

Ordinarily, when adults suffer the same problem as the girl who received the tissue-engineered blood vessel—a condition in which the vein that carries blood from the spleen and intestines to the liver is blocked—surgeons opt to transplant a patient’s own vein from the leg.  But this option is not feasible for young children because of the potential growth problems that can result from grafting in a still maturing body.

Christopher Breuer, a pediatric surgeon at the Yale University School of Medicine in New Haven, Connecticut, says the study represents an important next step for tissue-engineered technology. “This is a new application,” he notes. “This is the first time a bioengineered vein has been used in the portal circulation.”

As researchers try to make these procedures more routine, however, the use of stem cells on bioengineered grafts could face regulatory delays. “Whether real or not, regulatory agencies consider the risk of tumorogenesis or alterations in DNA a serious problem,” says Todd McAllister, cofounder and chief executive of Cytograft Tissue Engineering, a Novato, California company developing tissue-engineered blood vessels for people on dialysis for end-stage kidney disease.

Breuer, for one, is trying to overcome those obstacles. He is leading the first clinical trial in the US testing a tissue-engineered vascular product: a bioengineered blood vessel for children with a congenital heart defect. For more on his approach, see our 2011 news feature, ‘Taking tissue engineering to heart’.

Image courtesy of  Lightspring via Shutterstock

Texas resignation puts peer review under microscope

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In the wake of the resignation of its Nobel-Prize-winning scientific leader, the US$3-billion Cancer Prevention and Research Institute of Texas (CPRIT) is defending the integrity of its grant-making process.

Al Gilman, chief scientific officer of the CPRIT, based in Austin, resigned from his post on 8 May; his resignation letter was made public today by ScienceInsider. In the letter, ScienceInsider writes, Gilman “alludes to problems” with the institute’s peer-review system, warning that “negative decisions” made at the oversight committee’s next funding round in July “would have a fatal impact on CPRIT’s peer review system” and would “be extremely harmful to the research community’s view of science in Texas, and thus on the ability to recruit scientists to the state.”

In a letter released today, CPRIT chief executive Bill Gimson defends the institute’s peer-review process.

“As CPRIT’s founding chief scientific officer, [Gilman] helped shape the framework and policies that distinguish CPRIT’s research portfolio from other cancer research funding agencies,” Gimson writes. “Under Al’s leadership, CPRIT recruited the best peer review committees in the world while implementing a conflict-free system that is the cornerstone of our cancer research grant award process.”

In an e-mail, Gilman declined to elaborate on the issues he raised in his resignation letter.

CPRIT’s peer-review process is similar to that of the state-funded California Institute for Regenerative Medicine (CIRM), a stem-cell agency based in San Francisco. CPRIT peer reviewers all live and work outside the state, and their recommendations must be approved by the agency’s governing board.

But CIRM’s grant-approval process has been criticized for failing to exclude perceived conflicts of interest, most recently at a meeting convened by the US Institute of Medicine in April. A CIRM chief scientific officer, Marie Csete, also resigned from her post at the agency in 2009, although she did not cite problems with peer review as a reason.

Gilman’s resignation letter states that he will leave the CPRIT on 12 October. In an e-mail, he said he does not plan to revise that leaving date, “unless I am provoked to leave earlier”.

Follow Erika on Twitter at @Erika_Check.

 

What motivates you as a scientist?

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To tie in with the latest Nature Outlook, Lenses on Biology, the Nature Communities team asked five biological scientists at different stages of their education or careers to tell their personal stories in a guest blog post. Each scientist studies, works or has an interest in one of the five research fields featured in Lenses on Biology ― cancer, stem cells, synthetic biology, ocean health and climate change ― and they share what motivates them in their chosen subject. You can read their stories below, and discuss your own motivations here or on the posts in question.

Patients help bring the study of Alzheimer’s to the dish

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Israel et al. Supp Fig1: Experimental design.

Alzheimer’s disease (AD) is a devastating neurodegenerative disease that could become an even more massive public health problem than it already is, if current projections hold. Some predict that by 2050, 1 in 85 individuals will be affected by the disease. Currently, there is no cure, but there are neurotransmitter-enhancement-based strategies to slow down the cognitive deficits [the loss of cholinergic neurons is implicated in some of the memory problems associated with AD so therefore, pharmacological enhancement of brain acetylcholine concentration can partially alleviate some memory-based symptoms.] However, as with many neurodegenerative diseases, these stop-gap treatments only work for so long, until the cells responding to neurotransmitter supplementation treatments die off completely. Therefore, diverse strategies designed to cure or at least slow down AD are imperative.

While a number of AD transgenic mouse models have been created, based on the various mutations identified in patients, the trouble is that these models still utilize the cross-species approach of studying “diseased” mouse neurons expressing mutated human genes. And perhaps an even bigger problem with many mouse models, genetically-inherited forms of AD represent only ~0.1% of cases, with the remainder being “sporadic” (although there are genetic risk factors influencing the emergence of sporadic AD.)

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