Basic Research

Hitting our Goals: Let’s start at the beginning shall we

/ Kevin McCormack / Leave a comment

Way, way back in 2015 – seems like a lifetime ago doesn’t it – the team at CIRM sat down and planned out our Big 6 goals for the next five years. The end result was a Strategic Plan that was bold, ambitious and set us on course to do great things or kill ourselves trying. Well, looking back we can take some pride in saying we did a really fine job, hitting almost every goal and exceeding them in some cases. So, as we plan our next five-year Strategic Plan we thought it worthwhile to look back at where we started and what we achieved. Goal #3 was Discover.

When journalists write about science a lot of the attention is often focused on clinical trials. It’s not too surprising, that’s the stage where you see if treatments really work in people and not just in the lab. But long before you get to the clinical trial stage there’s a huge amount of work that has to be done. The starting point for that work is in the Discovery stage, if it works there it moves to the Translational stage, and only after that, assuming it’s still looking promising, does it start thinking about moving into the clinic.

The Discovery, or basic, stage of research is where ideas are tested to see if they have any promise and have the potential to lead to the development of a therapy or device that could ultimately help patients. In many ways the goal of Discovery research is to gain a better understanding of how, in our case, stem cells work, and how to harness that power to treat particular diseases or disorders.

Without a rigorous Discovery research program you can’t begin to create a pipeline of promising projects that you can advance towards patients. And of course having a strong Discovery program is not much use if you don’t have somewhere for those projects to advance to, namely Translational and ultimately clinical.

So, when we were laying out our Strategic Plan goals back in 2015 we wanted to create a pipeline for all three programs, moving the most promising ones forward. So we set an ambitious goal.

Introduce 50 new therapeutic or device candidates into development.

Now this doesn’t mean just fund 50 projects hoping to develop a new therapy or device. A lot of studies that are funded, particularly at the earliest stages, have a good idea that just doesn’t pan out. In fact one quite common definition of early research – in this case from Translational Medicine Communications – is “the earliest stage of research, conducted for the advancement of knowledge, often without any concern for its practical applications.

That’s not what we wanted. We aren’t in this to do research just for its own sake. We fund research because we want it to lead somewhere, we want it to have a practical application. We want to fund projects that actually ended up with something much more promising, a candidate that might actually work and was ready to move into the next level of research to test it further.

And we almost, almost made it to the 50-candidate goal. We got to 46 and almost certainly would have made it to 50 if we hadn’t run out of money. Even so, that’s pretty impressive. There are now 46 projects ready to move on, or are already moving on, to the next level of research.

Of course, there’s no guarantee that these will ultimately end up as an FDA-approved therapy or device. But if you don’t set goals, you’ll never score. And now, thanks to the passage of Proposition 14, we have a chance to support those projects as they move forward.

New stem cell could offer new ways to study birth defects

/ Kevin McCormack / Leave a comment

tony-parenti-stem-cell-2

Tony Parenti, MSU Ph.D student in cell and molecular biology

You never know what you are going to find in the trash. For a group of intrepid researchers at Michigan State University their discovery could lead to new ways of studying birth defects and other reproductive problems. Because what they found in what’s normally considered cellular trash was a new kind of stem cell.

The cell is called an induced extraembryonic endoderm stem (iXEN) cell. The team’s findings are reported in the journal Stem Cell Reports and here’s how lead author Tony Parenti described what they found:

“Other scientists may have seen these cells before, but they were considered to be defective, or cancer-like. Rather than ignore these cells that have been mislabeled as waste byproducts, we found gold in the garbage.”

Here’s the backstory to this discovery. For years researchers have considered embryonic stem cells as the “gold standard” for pluripotent cells, the kind that can be differentiated, or changed, into all kinds of cell in the body.

But studies in mice show that in addition to creating these pluripotent stem cells, the mouse embryo also produces extraembryonic endoderm or XEN cells. For a long time it was believed the gene expression of XEN cells affected the pluripotent stem cells, but the XEN cells were usually thought to be cancer-like, something that occurred as a byproduct of the developing embryo.

Searching through the trash

And that’s how things stayed until the research team at MSU noticed a bunch of XEN-like cells showing up every time they created induced pluripotent stem (iPS) cells – a kind of man-made equivalent of embryonic cells with the ability to turn into any other kind of cell but derived in a different way, reprogrammed from adult cells.

So they set out to see how important these, what they called induced or iXEN, cells were to the development of iPS cells. The researchers took  adult mouse cells and reprogrammed them into iPS cells and noticed colonies of iXEN cells in these cultures.

The first goal was to make sure these iXEN cells weren’t cancer-causing, as many researchers believed. This took six months but at the end of it not only were they able to demonstrate that the cells aren’t cancer-causing in a cell culture dish, but that they are a new type of stem cell.

Next step was to see how important endodermal genes are in the formation of iXEN cells. They found that decreasing endodermal gene expression led to a two-fold decrease in the number of iXEN cells and a significant increase in the number of iPS cells.

Competitors not collaborators

They concluded that the parallel pathways that generate pluripotent and XEN cells are in competition with each other and not in support of each other during reprogramming. By suppressing one they were able to boost the other. To their delight they had stumbled on a more efficient way of creating iPS cells.

While the discovery of a new kind of stem cell is always exciting there’s a catch to this; we still don’t know if XEN cells are found in humans. But this discovery gives the researchers additional tools to try and find the answer to that question.

Amy Ralston, a co-author of the study, said in a news release:

“It’s a missing tool that we don’t have yet. It’s true that XEN cells have characteristics that pluripotent stem cells do not have. Because of those traits, iXEN cells can shed light on reproductive diseases. If we can continue to unlock the secrets of iXEN cells, we may be able to improve induced pluripotent stem cell quality and lay the groundwork for future research on tissues that protect and nourish the human embryo.”

Normally the discovery of anything new, particularly when it over turns a long-held belief, is met with a degree of healthy skepticism at first. In science that’s a good thing. We all remember the eager way that STAP stem cells were hailed by many as a new way to create pluripotent stem cells until the research was discredited. But so far the Twitterverse and media outlets seems to share in the excitement about this discovery.