Stem Cell Word Cloud: Mesenchymal Dominates in 2015

What does a stem cell word cloud tell us about the field?

Word clouds are fun and informative ways to do textual data mining. I’ve done some in the past that have providing penetrating looks at science including at the whole field of science in 2014.Stem Cell Word Cloud 2015

What has the stem cell field overall been focusing on lately?

I turned to a word cloud to figure it out from the thousands of articles out there.

Above is a word cloud made from all the titles of 2015 articles with “stem cell” or “stem cells” in the title using a simple PubMed search and the WordItOut online tool.

Larger words are used more often. Note that the search terms, “stem”, “cell”, and “cells” were removed along with most commonly used words like “the”.

The word “mesenchymal” stands out as the top word by far.

Substantially smaller are other types of stem cells including “hematopoietic” and even smaller “embryonic” and “pluripotent”. That difference may reflect a significant difference in overall focus for the field. Mesenchymal stem cells are arguably the hottest type of stem cell in 2015 in the field overall. This search could have a bias against IPS cells since my PubMed search focusing on “stem cell(s)” would miss titles with “IPSC” or “IPS cells” in the title without “stem cell(s)” in the same title.

Also standing out as top-used words in stem cell article titles are “human” and “transplantation”, which is an encouraging indication of a focus on getting stem cells translated to the bedside to help patients.

It’s nice to see “differentiation” being an often-used word because so much more emphasis is needed on stem cell differentiation. Coming next in size are “bone” and “cancer”.

Overall, this stem cell word cloud provides a novel window into what the field is publishing this year.

Cloning is cloned again: New Nature Paper is 3rd on Human SCNT

A new human therapeutic cloning paper is out today, the third in a matter of months. This one is from the lab group of Dr. Dieter Egli published in Nature demonstrating production of nuclear transfer embryonic stem cells (NT-ESCs) from an adult human somatic donor via somatic cell nuclear transfer (SCNT).

This human SCNT paper follows on the heels of a similar paper (Chung, et al.) from Bob Lanza’s group published in Cell Stem Cell and the pioneering Mitalipov human SCNT paper (Tachibani, et al.) in Cell in 2013.

Together these three papers have proven that human therapeutic cloning to make patient-specific ES cells is absolutely the real deal and that it presents a new therapeutic option based on stem cells in the years and decades to come.

This Egli group paper, Yamada, et al., is entitled “Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells”.

Yamada Extended Data SCNT

So what’s the scoop on this new Yamada human SCNT paper?

The main conclusions fit with those of the previous Tachibani and Chung papers. Oddly enough, one of the most important sets of data is tucked away as Extended Data Figure 8 (see above) that nicely summarizes the paper’s data.

There are some additional technical data that may prove useful for additional labs to make NT-ESCs by therapeutic cloning of human somatic cells such as surprisingly the inclusion of fetal bovine serum (FBS; see the figure above, the far right two columns showing that addition of FBS seems to really boost the process of making NT-ESC lines.

This team also made NT-ESC from a Type I Diabetic patient highlighting the future clinical potential of this technology.

What about the bigger picture?

As I mentioned in a previous post providing broader perspectives on translating human NT-ESCs to the clinic there are some key challenges and I list the top 5 hurdles. I called human therapeutic cloning to make NT-ESCs the stem cell story of the year for 2013.

It’s still a very big deal in 2014. The two new 2014 human SCNT papers just raise the intensity of this story to another level. It will be a fascinating story to continue to follow.

BioTime CEO Mike West Interview Part 2: Geron & hESC

GeronWho do you turn to when you want to both know the real history of the pluripotent stem cell-based biotech industry and perspectives on its future?

There are only a handful of people and one of them is definitely Dr. Michael West, CEO of BioTime.

I’m doing a several part series of blog posts on a lengthy phone interview and conversation that I had with West.

Today in Part 2 we are focused on clinical development of human ES cells and what happened with Geron.

You can see Part 1 here on the history of the field.

By way of background, for a time Geron led the way in clinical translation of ES cell-based therapies having the first and for a time the only human ES cell-based FDA approved clinical trial.

Today the picture is quite different as Advanced Cell Technology (ACT; ACTC) is the only company currently with active FDA-approved clinical trials for transplantation of an ES cell-based product.

Part of the reason for this new reality is that Geron, under new management, made the decision to drop its ES cell program for treatment of spinal cord injury.

I asked West about what happened with Geron, meaning why Geron gave up on its stem cell clinical trial in November 2011. His initial reaction:

“I was amazed and dismayed at the discontinuation of the program.”

Despite some issues with the Geron stem cell program described to me by West (including a key, but not insurmountable flaw that is a challenge for almost the entire stem cell field according to West that I will discuss in Part 3 of this series), West felt Geron could have proceeded with the program.

However, West said it may have been that “new management struggled with issues of process development, purity, identity, that sort of thing, hurdles in the path to bringing their products to market. I wasn’t there at the time, so these are only educated guesses based on the similar problems some other CIRM-funded researchers are having.”

In part that new management was new CEO John Scarlett, who replaced Thomas Okarma.

What I heard at the time was that Scarlett was a “cancer guy” whereas Okarma was more of a “stem cell guy” and that difference may have had something to do with the decision. However, now I’m not so sure it was that simple.

At the time, one of the challenges that Geron faced was that its oligodendrocyte/oligodendroglial precursor cell (OPC) product made from human ES cells had formed cysts in animals transplanted with the OPC product.

Eventually the FDA green lighted Geron to proceed, lifting the hold.

However, West told me he had concerns longer term:

“….just because a hold is lifted and an early trial proceeds, doesn’t mean the FDA would ever give final approval to market a product in the end”.

This concern may have been at the heart of Geron’s decision to move on from stem cells, but West made it clear he believes in this research and its clinical application.

West is of course now pursuing the continuation of this former Geron stem cell trial in a new incarnation via BioTime. While West indicated that the deal between Geron and BioTime is not yet official, I don’t see any reason it won’t be finalized.

In Part 3 of this series, I talk with West about the key flaw in the approach of so much of the pluripotent stem cell field and indeed the stem cell field more generally in some respects.

Later in the series I will discuss West’s proposed solution.

The myth of stem cells as a zero sum game

One of the most common myths is that stem cells are a zero sum game.

What’s a zero sum game?

It’s a dynamic where the overall good in a given situation or system stays the same.

What this means is that in a zero sum game, if something is good for one person, it must be bad for someone else because the overall net situation does not

There are real zero sum games in life, but the stem cell field is not one of them.

A great example of a real zero sum game is a pizza to be divided amongst a group of people. Every piece eaten by one person means one less for the others. There is no way around that.

In the stem cell world, some ideologues incorrectly view stem cells as a zero sum game.

In this mythical stem cell world, what is good for one type of stem cells must automatically be bad for another different kind of stem cells.

Usually the zero sum game players believe that what is good for adult stem cells must be bad for embryonic stem cells and vice versa. Interestingly, by contrast, a person advocating for embryonic stem cells correctly seems adult stem cell work not as some kind of enemy, but rather as something positive.

The stem cell zero sum gamers desperately try to promote bad things about embryonic stem cells in the foolish belief that as a result they’ll be helping adult stem cells.

They also believe that any positive thing for embryonic stem cells must be bad for adult stem cells so they attack any claim of the possible positives of embryonic stem cells.

Some of them are even now attacking iPS cells and iPS cell researchers as somehow being biased against adult stem cells and adult stem cell clinics. It just doesn’t make any sense.

Stem cells are not a zero sum game.

In fact, what is good for one type of stem cells is usually also good for other types of stem cells.

It’s not a competition.

Knowledge about embryonic stem cells can actually inform adult stem cell work and vice versa. The advancements with iPS cells are a great example of how knowledge from embryonic stem cells can advance non-embryonic stem cell work.

Stem cell advances in adult, embryonic, and iPS cells are a win-win-win situation, not a zero sum game.

Stem cell field reacts somewhat cautiously to mammary pluripotent stem cell paper

An interesting paper just came out in PNAS reporting the apparent presence of pluripotent stem cells in the adult breast.

The paper is Roy, et al. and is from Thea Tlsty’s outstanding lab at UCSF.

I have read the paper and it seems very solid technically to me.

The finding has stimulated some powerful metaphors. For example, The San Francisco Business Journal called the paper an “Earthquake” for the field.

ePS cells

I have asked some leaders in the field behind the scenes for their impressions of the finding. Their reaction can be summed up as cautious interest.

One concern raised about the finding is that it is difficult to understand why the adult breast would need to have pluripotent stem cells. While the breast has inherent plasticity required for being able to gear up for milk production, why would the breast need stem cells that can make totally unrelated tissues?

Pancreas? Skin? Heart? Cartilage? Brain? (See image above of differentiation potential of ePS cells).


Mother nature usually makes good sense and there is an intrinsic logic in terms of how it works. Some people have said to me that the adult breast just does not need pluripotent stem cells so why would they be there? I don’t know, but just because it seems illogical for the breast to have pluripotent stem cells does not mean the paper is off-base, but it has made some experts cautious.

It is worth noting that just last year (2012), a paper (Hassiotou, et al) in the journal Stem Cells reported the presence of pluripotent stem cells in breast milk. Puzzlingly, the new 2013 Roy paper did not cite this 2012 paper at all. I find that concerning.

The reported stem cells in the new 2013 paper, what the authors called “endogenous pluripotent somatic” or ePS cells, are not identical to embryonic stem (ES) cells as the ePS cells are mortal, which means they will stop growing over time in the lab. ES cells are immortal and will grow forever. The lack of immortality of ePS cells is likely a good thing because it would make them safer. Also, ePS cells, if recapitulated, have another positive and that is no embryos are needed to make them.

The SF Biz Journal article says that the ePS cells are found in other adult tissues as well and in men:

Preliminary data suggest that ePS cells exist in parts of the body beyond adult breast tissue, Tlsty said, and in men as well as women.

“We have no idea if they’re different by gender,” she said.

EPS cells don’t appear to be left behind by embryonic stem cells, like pieces of bread dropped on a path to help someone find the way home, Tlsty said. The ePS cells, she said, have different expressions, surface markers and other characteristics than those found with embryonic stem cells.

CIRM itself has reacted publicly in a somewhat cautious manner to the paper as well:

“This really could be very exciting,” said Patricia Olson, executive director of scientific activities at the San Francisco-based California Institute for Regenerative Medicine, or CIRM. “If verified, I think it could be a big deal.”

Bottom line. Let’s see how this develops and whether the work can be verified without getting too overexuberant just yet. I hope that this finding on ePS cells holds up and is recapitulated by other labs. It would be exciting.