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.
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.