Advancing stem cell research in many ways

Speakers at the Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

From Day One CIRM’s goal has been to advance stem cell research in California. We don’t do that just by funding the most promising research -though the 51 clinical trials we have funded to date clearly shows we do that rather well – but also by trying to bring the best minds in the field together to overcome problems.

Over the years we have held conferences, workshops and symposiums on everything from Parkinson’s disease, cerebral palsy and tissue engineering. Each one attracted the key players and stakeholders in the field, brainstorming ideas to get past obstacles and to explore new ways of developing therapies. It’s an attempt to get scientists, who would normally be rivals or competitors, to collaborate and partner together in finding the best way forward.

It’s not easy to do, and the results are not always obvious right away, but it is essential if we hope to live up to our mission of accelerating stem cell therapies to patients with unmet medical needs.

For example. This past week we helped organize two big events and were participants in another.

The first event we pulled together, in partnership with Cedars-Sinai Medical Center, was a workshop called “Brainstorm Neurodegeneration”. It brought together leaders in stem cell research, genomics, big data, patient advocacy and the Food and Drug Administration (FDA) to tackle some of the issues that have hampered progress in finding treatments for things like Parkinson’s, Alzheimer’s, ALS and Huntington’s disease.

We rather ambitiously subtitled the workshop “a cutting-edge meeting to disrupt the field” and while the two days of discussions didn’t resolve all the problems facing us it did produce some fascinating ideas and some tantalizing glimpses at ways to advance the field.

Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

Two days later we partnered with UC San Francisco to host the Fourth Annual CIRM Alpha Stem Cell Clinics Network Symposium. This brought together the scientists who develop therapies, the doctors and nurses who deliver them, and the patients who are in need of them. The theme was “The Past, Present & Future of Regenerative Medicine” and included both a look at the initial discoveries in gene therapy that led us to where we are now as well as a look to the future when cellular therapies, we believe, will become a routine option for patients. 

Bringing these different groups together is important for us. We feel each has a key role to play in moving these projects and out of the lab and into clinical trials and that it is only by working together that they can succeed in producing the treatments and cures patients so desperately need.

Cierra Jackson: Photo by Marco Sanchez

As always it was the patients who surprised us. One, Cierra Danielle Jackson, talked about what it was like to be cured of her sickle cell disease. I think it’s fair to say that most in the audience expected Cierra to talk about her delight at no longer having the crippling and life-threatening condition. And she did. But she also talked about how hard it was adjusting to this new reality.

Cierra said sickle cell disease had been a part of her life for all her life, it shaped her daily life and her relationships with her family and many others. So, to suddenly have that no longer be a part of her caused a kind of identity crisis. Who was she now that she was no longer someone with sickle cell disease?

She talked about how people with most diseases were normal before they got sick, and will be normal after they are cured. But for people with sickle cell, being sick is all they have known. That was their normal. And now they have to adjust to a new normal.

It was a powerful reminder to everyone that in developing new treatments we have to consider the whole person, their psychological and emotional sides as well as the physical.

CIRM’s Dr. Maria Millan (right) at a panel presentation at the Stanford Drug Discovery Symposium. Panel from left to right are: James Doroshow, NCI; Sandy Weill, former CEO Citigroup; Allan Jones, CEO Allen Institute

And so on to the third event we were part of, the Stanford Drug Discovery Symposium. This was a high level, invitation-only scientific meeting that included some heavy hitters – such as Nobel Prize winners Paul Berg and  Randy Schekman, former FDA Commissioner Robert Califf. Over the course of two days they examined the role that philanthropy plays in advancing research, the increasingly important role of immunotherapy in battling diseases like cancer and how tools such as artificial intelligence and big data are shaping the future.

CIRM’s President and CEO, Dr. Maria Millan, was one of those invited to speak and she talked about how California’s investment in stem cell research is delivering Something Better than Hope – which by a happy coincidence is the title of our 2018 Annual Report. She highlighted some of the 51 clinical trials we have funded, and the lives that have been changed and saved by this research.

The presentations at these conferences and workshops are important, but so too are the conversations that happen outside the auditorium, over lunch or at coffee. Many great collaborations have happened when scientists get a chance to share ideas, or when researchers talk to patients about their ideas for a successful clinical trial.

It’s amazing what happens when you bring people together who might otherwise never have met. The ideas they come up with can change the world.

Stem cell stories that caught our eye: reality check on chimeras, iPS cells for drug discovery and cell family history

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

iPS cells becoming foot soldiers of drug discovery. Here at The Stem Cellar we write often about the power of iPS-type stem cells to model disease and accelerate drug development. This week provided a couple of strong reminders of the value of these induced pluripotent stem cells that researchers create by reprogramming any adult cell, usually skin or blood, into an embryonic stem cell-like state.

Researchers at Penn State University published work that used iPS cells from patients with Rett Syndrome to find a target for drug therapy for that severe form of autism spectrum disorder. After turning the stem cells into nerves they found those cells lacked a protein that is critical to the function of the neural transmitter GABA. That protein has now become a target for drug therapy. As a bonus for the field, the study, published in the Proceedings of the National Academy of Sciences, provided an explanation for why a drug already in clinical trials for Rett Syndrome might work. That drug is IGF1, insulin-like growth factor. The web site Medical News Today wrote up the research.

Later in the week an announcement popped up in my email for the two-day “inaugural” conference “Advances in iPS cell Technology for Drug Development Applications.” The field clearly has momentum. CIRM has funded a bank that will eventually house up to 3,000 cell lines relating to specific diseases. So far, 285 lines are available to researchers anywhere, 14 of them Autism spectrum lines, through the tissue banks at Coriell.

 

Tracking a cell’s family history. When cells divide their offspring can have a different identity from the mother cells. This occurs commonly in stem cells, as they mature into adult tissue, and in the immune system as cells respond to infections. Knowing the genetic details of how this happens could accelerate both stem cell science and our ability to understand and manipulate the immune system.

A team at MIT has taken us a step closer to this ability. They married a trendy new technique called single cell genetic analysis with a fluidic device that can isolate single cells in one chamber and daughter and grand daughter cells in subsequent chambers. In this case, they used single cell RNA-seq, the shorthand for sequencing. They wanted to know the differences between the cells in terms of genes that are actually active, and since the RNA representing a gene is only made when the gene is active, this provided a snapshot of each cell’s genetic identity.

Genetic Engineering News wrote about the work and quoted the lead author of the study Robert Kimmerling:

“Scientists have well-established methods for resolving diverse subsets of a population, but one thing that’s not very well worked out is how this diversity is generated. That’s the key question we were targeting: how a single founding cell gives rise to very diverse progeny.”

This new combined system should let researchers investigate how this happens. The MIT team started by looking at how one immune system cell can produce both the cells that attack and kill invaders and the cells that stick around and remember what the invaders looked like.

 

Human-animal chimeras, what are labs really doing. Antonio Regalado did a thorough piece in MIT Technology Review examining the work of the few labs around the country that are trying to grow human tissue in animal embryos—chimeras. He estimates that some 20 pig-human or sheep-human pregnancies have been established, but no one is letting those embryos grow more than a very few weeks. Their immediate goal is to better understand how the cells with different origins interact, not to breed chimeric animals.

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A pig at the UC Davis research center

One long-term goal is, for example, to grow a personalized new pancreas for diabetic patients who needs a new one of those insulin-producing organs. But no one in the field expects that to happen anytime soon. The process involves using modern genetic editing techniques to turn off the genes that would make a particular organ in the animal embryo, inserting human stem cells and hoping the growing embryo will hijack the genes for making the equivalent human organ, but not other human tissues.

The embryos examined so far have generally contained a very small amount of human DNA, less than one percent in a project at Stanford. So, probably not enough to give the animal human traits beyond the organ desired. Pablo Ross who has done some of the early work at the University of California, Davis explained the intent of those studies is “to determine the ideal conditions for generating human-animal chimeras.”

It is fascinating work and has great potential to alleviate organ shortages, but will require several more breakthroughs and much patience before that happens.