Spotlight on CIRM Grantee Joe Wu: Clinical Trials for Heart Disease in a Dish?

It’s always exciting to read a science article featuring a talented scientist who is breaking boundaries in the field of regenerative medicine. It’s especially exciting to us at CIRM when the scientist is a CIRM grantee.

Last week, OZY published a fun and inspiring piece on Stanford scientist Joe Wu. Dr. Wu is the Director of the Stanford Cardiovascular Institute and his lab studies how stem cells (both adult and pluripotent) function and how they can be used to model heart diseases and screen for new drug therapies. He also is a CIRM grantee and has a Disease Team Therapy Development grant that aims to clinically test human embryonic stem cell-derived cardiomyocytes (heart cells) in end stage heart failure patients.

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

Dr. Joe Wu. (Image Source: Sean Culligan/OZY)

The OZY piece does a great job of highlighting Dr. Wu’s recent efforts to use human induced pluripotent stem cells (iPS cells) to make heart tissue in a dish and model cardiovascular disease. And without getting too technical, the article explains Dr. Wu’s larger mission to combine precision medicine and stem cell research to identify drugs that would be best suited for specific patient populations.

The article commented,

“He envisions treatments based on an individual’s own iPS cells. For example, a popular breast cancer drug has an 8 percent chance of giving patients heart failure. In Wu’s world, we’d test the drug on stem cells first, and if a patient lands in that 8 percent, begin treatment for the side effects preemptively or avoiding the drug totally and avoiding heart failure, too.”

Basically, Dr. Wu sees the future of clinical trials in a dish using human stem cells. “His goal is to take these stem cells from thousands of patients to create a genetically diverse enough bank that will allow for “clinical trials in a dish” — Wu’s go-to phrase.”

Instead of following the traditional drug development paradigm that takes more than 10 years, billions of dollars, and unfortunately usually ends in failure, Dr. Wu wants to follow an accelerated path where stem cells are used for drug toxicity and efficacy testing.

This alternative path could improve overall drug development and approval by the FDA. The article explained,

“Testing drugs on stem cells will give big pharma and the FDA vastly improved heads up for toxic complications. Stem cells are “absolutely” the best avenue going forward, says Norman Stockbridge, director of the division of cardiovascular and renal products at the FDA’s Center for Drug Evaluation and Research.”

Not everyone is on the same page with Dr. Wu’s bold vision of the future of precision medicine, stem cells, and treatments for heart disease. Some believe he is overly ambitious, however top scientists in the stem cell field have praised Dr. Wu’s “systematic approach” to research and how he doesn’t stop at data discovery, he focuses on the big picture and how his work can ultimately help patients.

You can read more about Dr. Wu’s research on his lab website and I highly encourage you to check out the OZY article which is a great example of science communication for the general public.

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Embryonic and man-made stem cells are almost identical

iPS cell

iPS cell

Embryonic stem cells

Embryonic stem cells

For years it has been the stem cell equivalent of the feud between the Hatfields and McCoys. The dispute centered on the question of which is better for advancing scientific research and developing new therapies, embryonic stem (ES) cells or induced pluripotent stem (iPS) cells?

The somewhat surprising answer may be that they are both pretty much the same, at least according to a new study in the journal Nature Biotechnology.

For years many researchers felt that ES cells were better because they knew more about them and had a deeper understanding of how they worked. However, because ES cells are derived from human embryos they also carry ethical baggage for some people.

In contrast iPS cells are made from skin cells, or other adult cells, that have been reprogrammed to behave in an embryonic-like way and, like an ES cell, have the ability to turn into any other kind of cell in the body. However, some earlier studies had raised questions about iPS cells, after genetic variations were found in some batches, suggesting that the very act of creating the cells was causing potentially dangerous mutations.

This new study seems to calm those fears, confirming that these variations are due to differences that existed in the original skin cells that the iPS cells were made from, and did not arise during the reprogramming process.

The researchers, led by Konrad Hochedlinger of Massachusetts General Hospital in Boston, took two lines of ES cells and allowed them to mature into adult cells before reprogramming them into iPS cells. They were then able to analyze the iPS cells and measure gene activity in them to see how alike or different they were compared to the original ES cells.

They found that even though they were made from ES cells the iPS cells differed in some of their gene activity from their “parents”. However, when they examined if these variations changed the cells’ abilities to function they found no differences.

Equally important was the finding that ES and iPS cells were both equally good at being able to change into a variety of nervous system cells.

“The two cell types appear functionally indistinguishable based on the assays we used,” Hochedlinger said.

The magazine Science quotes two CIRM-funded scientists, neither of who were involved in the study, weighing in on its findings. Joseph Wu of Stanford said:

“I think it was a very well done study, and it will ease some of the concerns about ES cells versus iPS cells.”

William Lowry of the University of California, Los Angeles agreed:

“It’s probably going to be a lot easier to go forward with iPS cells because of studies like this.”

Science being science it is unlikely this one study will completely end the debate, and there are still many researchers who will prefer to use ES cells for their work because they are much more familiar with them. Nonetheless this may at least take some of the heat out of the debate and create an easier path for approval from the Food and Drug Administration (FDA) for researchers who hope to use iPS cell-based treatments in people.