Guest blogger Alan Trounson — October’s stem cell research highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

This month’s lead story garnered considerable media attention. A team at the New York Stem Cell Foundation succeeded in creating embryonic stem cell lines through nuclear transfer, sometimes called cloning. The actual science of what the group did has already been covered in this blog (read the blog entry here). Now, I am suggesting that, because the trick they used to get the cloning to work resulted in cells with three sets of chromosomes, the follow-on research that tries to understand why their method worked may produce much more useful data than the original breakthrough. I look forward to reading those next papers.

October also produced another salvo in the back and forth over how useful iPS cells— the stem cells that result from reprograming adult cells—really are. Early this year, a few papers appeared suggesting iPS cells had considerably more genetic defects than their embryonic counterparts. Now a team at Scripps and University of Virginia using a somewhat different reprogramming technique, and a 30-fold better method of gene analysis, found almost no gene defects attributable to the reprogramming. The last chapter in this saga is far from being written.

At a time when it seems like teams announce the full gene sequences of another animal or bacteria weekly, saying that a paper on gene sequencing is important to our field may appear to be a stretch. However, when BioTime announced that they had sequenced five of their clinical grade embryonic cell lines, it did allow us to tick the box on an important milestone for our field. Many observers believe the FDA may start to demand some sort of evidence of the genetic integrity of cell lines that are going into clinical trials. So, having these lines available could indeed accelerate our pace to the clinic.

I hope you find my full report on this month's science picks interesting.

- Alan Trounson

Guest blogger Alan Trounson — September’s stem cell research highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

Much good science and important science does not qualify as a “breakthrough.” Turning stem cells into heart cells is nothing new. Many teams have done it with both embryonic stem cells and reprogrammed, or induced Pluripotent Stem Cells (iPSC).

However, most the methods for steering stem cells down the path toward heart tissue are not very efficient or don’t produce uniform heart cells. You often end up with a mixed batch of cell types. This month’s literature produced the type of incremental advance that does not wow you, but is exactly the type of thing we need to make the field more practical for patients looking forward.

A team at Kyoto University reported an efficient way to make heart progenitor cells from both embryonic and iPSCs. But more important they found a cell surface marker on those progenitor cells that let them develop an efficient and scalable purification method to get and end product that was just the cells they wanted. But even this step was not easy. They screened 242 antibodies to find this one marker.

My full report of this month’s highlights has some similar incremental advances in improving bone marrow transplant as well as a few other papers I hope you will find interesting.

Guest blogger Alan Trounson — August’s stem cell research highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

This month produced several papers that address fundamental issues in the field of stem cell research and provided us with some rebuttal points for one-liners tossed at us by some of our critics. If you have followed the field you’ve heard detractors of embryonic stem cells say: “why are we wasting our time on a cell type that causes tumors.” That is because in their most primitive pluripotent state embryonic stem cells form a type of tumor called a teratoma. While no one has ever planned to place a still-pluripotent embryonic stem cell in a patient—the plan has always been to mature them into tissue-specific cells first—the criticism has remained. Now, a team at Stanford has shown a way of completely purifying those progenitor cells and removing all the pluripotent cells capable of forming a tumor. (We blogged about that work here.)

Our critics also state that embryonic stem cells are by nature “anti-life” because a very early stage embryo is destroyed isolating them. But now a Japanese team has succeeded in reliably and efficiently producing viable sperm from embryonic stem cells. The follow-on research to this project could go a long way to reducing infertility around the globe. And that is certainly a pro-life outcome.

Finally a series of articles dealt with a very real and looming issue for the field. What is the role for sham surgery, mimicking the placement of cells, in controlled clinical trials for cell-based therapies. This has become a particularly contentious issue in Parkinson’s disease where there is shown to be a physiologic reason for a strong placebo effect. If you are interested in this question I encourage you to read the three pieces cited in my literature summary this month.

Guest blogger Alan Trounson — July’s stem cell research highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

In the past month one paper struck me as especially important because it has the potential to alleviate a particularly nasty disability. Radiation therapy can buy time for patients with brain tumors, but the collateral damage it does to surrounding healthy tissue can cause problems with learning and memory, that grow worse over time. It is believed that this decline occurs because the radiation destroys the adult neural stem cells that should be repairing damage. When this happens to a child and you watch them decline mentally at an age when they should be advancing, it can be heart-breaking. That is why I chose to highlight a paper in which injected neural stem cells were able to repair radiation damage in rats and bring back their sensory abilities towards normal. (You can read our blog entry on this research here.)

This month’s literature continued to show progress in using stem cells to reproduce complex tissues made of multiple cell types, something that has always been a touchstone goal for regenerative medicine. One research team was able to grow functional small intestine on a biodegradable scaffold in mice (which we blog about here). Another was able to produce mucus glands with both the inner and outer structures that make up a normal gland (blogged about here).

With heart disease being a leading cause of disability it was good to see advances in heart tissue repair this month from two very different angles. One research team developed a much more efficient way to drive embryonic stem cells to become heart muscle cells, which is the type of cell needed to repair tissue damaged or weakened from a heart attack or congestive heart failure. The other team discovered a compound that can be injected like a drug and that can activate the few adult heart stem cells we all have to be better at repairing tissue (here's our blog about that work).

I hope you find the somewhat longer descriptions in my full report interesting.

Guest blogger Alan Trounson — May’s stem cell highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

The first paper I highlight in this month’s summary, purporting to have found master lung stem cells, is already generating controversy. (See our blog entry: Lung stem cell found, controversy ensues) Scientists have generally not been believed that one set of adult stem cells could generate all the types of tissues required to form complex mature lung. Regardless of whether others are able to reproduce this work, it is sure to generate interest because advances in the field of regenerating healthy lung tissue is something that could benefit millions of severely disabled patients.

This month’s literature continued to produce a yin and yang of good news and disappointment for reprogrammed cells. It saw one team directly reprogram skin tissue into functional liver cells and another produce a model of schizophrenia in a lab dish (See From stem cell to schizophrenia in a dish). That paper showed real differences between neurons grown from iPS cells made from normal individuals and those with the disease—and those differences could yield drug targets. But the literature also revealed that iPS cells could face immune rejection even when they are transplanted into an animal that is genetically matched. (See iPS cell smack down) We have to continuously tell ourselves that the iPS field is only five years old and these mixed results will get worked out and understood over time.

As we move closer to the clinic, we are increasingly concerned with efficiency of cell production and getting quantities of cells sufficient to run a clinical trial. This month saw papers greatly improving the efficiency of generating blood precursor cells from embryonic and induced stem cells and of generating neural precursor cells from embryonic stem cells.

Last, is a paper that offers some hope for my hair follicle challenged colleagues. Actively growing patches of hair appear to require some level of cross talk between hair stem cells. But this paper does have a more serous note. This same communication between stem cells may be critical in tissues like the intestine that have rapid cell turn over.

I hope you find the somewhat longer descriptions in my full report interesting.

Guest blogger Alan Trounson - April's stem cell highlights

Alan Trounson is President of CIRM

Since I arrived at CIRM late in 2007 I have maintained a tradition of presenting some of the top science journal papers from the previous month or two at each of our Board meetings. Beginning last month, I decided this would be easier to digest in a written document than in PowerPoint slides amid a harried board meeting. You can see an archive of these periodic stem cell reports on our website.

This month I want to start a second part of the new tradition, a brief blog note to let you know why I, as someone who toiled in stem cell labs for many years, chose these items as some of the most important papers in the field in the past month or so.

The first paper is a true breakthrough, something no one had accomplished before. A Japanese team was able to create an “organized” tissue in a dish, not just drive stem cells to become a specific adult cell, but rather two types of cells in two distinct layers. In this case they created an optic cup that resembled a post-natal retina. With one of the holy grails of stem cell research being the ability to replace complex organs, this was a brilliant paper to see.

You will see that in last month’s stem cell report I discussed “this year’s problem” with iPS, or reprogrammed cells, which is their much higher rate of genetic anomalies compared to embryonic stem cells (as we blogged about here). Well, this month I am discussing “last year’s problems” with iPS cells. For the past couple years there has been much hand wringing about the possibility that the transcription factors used to reprogram cells, if left in the cells, could be turned on at the wrong time and lead to cancer, and that the reprogramming processes were all hugely inefficient. Now, only five years after the first iPS cells were created in mice, a number of papers came out this month showing major strides to reprogramming with only transient integration of the reprogramming factors and exponential improvement in efficiency in creating iPS cells. I have to hope that “this year’s” iPS problem will be even more quickly solved or at least its relevance determined.

Last, I chose a paper that does two things: it explains a clinical result that had many purists in the fields shaking their heads in doubt and points the way to another major goal of the field, a way to stimulate endogenous stem cells to make repairs when needed. The study found a protein that can induce endogenous stem cells in heart attack patients and may explain why certain bone marrow stem cells, ones that have no ability to form heart tissue, nonetheless seem to offer some small but genuine improvement for many patients.

Alan Trounson

Nobel-winning IVF work laid groundwork for stem cell research

On Monday the Nobel Prize in Physiology or Medicine went to Robert Edwards for his efforts to make in vitro fertilization a reality. The Nobel Prize-winning discovery not only allowed millions of couples to start families, it opened up the field of stem cell research.

According to the Nobel Prize press release:

Approximately four million individuals have so far been born following IVF. Many of them are now adult and some have already become parents. A new field of medicine has emerged, with Robert Edwards leading the process all the way from the fundamental discoveries to the current, successful IVF therapy. His contributions represent a milestone in the development of modern medicine.

Alan Trouson, CIRM president, was in the thick of the early IVF work. He led the team that produced Australia's first IVF baby -- the third in the world. He went on to develop ways of using fertility drugs and freezing embryos to increase the success rate of IVF. He was also among the first to realize the possibilities of taking stem cells from the unused embryos to create cells with the potential to become every cell in the body.

As a sign of how far the IVF field has come, on the same day that Edwards won his Nobel Prize researchers at Stanford University published work showing a technique for selecting which embryos have a 90% chance of resulting in a healthy blastocyst -- a stage of development at about 5 days old, when the embryo is implanted into the mother's womb.

According to a Stanford press release, about 2/3 of embryos created through IVF normally die. Improving those odds could greatly increase the rate of successful IVF pregnancies. The work was led by Renee Reijo Pera, who is also a CIRM grantee (Comprehensive Award and New Cell Lines Award). The release goes on the say:

“It completely surprised me that we could predict embryonic fate so well and so early,” said Reijo Pera. If an embryo’s values fell within certain windows of time for the three predictive parameters, that embryo was more than 90 percent likely to go on to develop successfully into a blastocyst.

Being able to predict which embryos will survive greatly improves a woman's chance of getting pregnant. Riejo Pera is quoted in the release as saying:

"Women, their families and their physicians want to increase the chances of having one healthy baby and avoid high-risk pregnancies, miscarriages or other adverse maternal and fetal outcomes. It’s truly a women’s health issue that affects the broader family.”

Reijo Pera stressed the importance of the work in understanding the earliest stages of human development, where many developmental anomalies are though to originate. It could also be important for the creation of new embryonic stem cell lines, which come from embryos that are discarded from IVF clinics.