Cancer stem cells are one of the most interesting areas of research, intersecting the stem cell and cancer fields. Today’s weekly reads post highlights some new cancer stem cell articles along with some other interesting papers.
I also note a recent weak stem cell clinical trial paper that is not a recommended read but is puzzling. I discuss the issues involved.
Villin-CreERT2;Red2-KrasG12D mice 2 days after tamoxifen
administration (representative of three independent experiments). White
dashed line, mucosal lining. Bottom right shows crypt fission (arrow) and
fusion events (arrowhead). Kyu Yum, et al. Nature.
Cancer stem cells
- Cancer stem cells in the gut have a bad influence on neighbouring cells, Nature. Non-cell autonomous mechanisms in cancer are likely quite important in the niche.
- Tracing oncogene-driven remodelling of the intestinal stem cell niche, Nature. Here’s another niche paper. It has some very striking figures. See a screenshot of Fig. 1c above.
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ASCL1 represses a SOX9+ neural crest stem-like state in small cell lung cancer, G&D. My lab’s paper last summer on mutant histone H3.3 in childhood glioma found ASCL1 to be a likely major mediator of some of the tumorigenic effects. Note that small cell lung cancer is a neuroendocrine tumor.
More pubs
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Phase separation of OCT4 controls TAD reorganization to promote cell fate transitions, Cell Stem Cell.
Puzzling stem cells for diabetes article in SCTM
The journal Stem Cells Translational Medicine got some attention in recent weeks for some back and forth related to controversial papers it has published on cord blood and other unproven approaches to autism.
Now UPI picked up (Stem cell therapy could reverse Type 2 diabetes for some) a stem cell-related article in Stem Cell Translational Medicine that again seems puzzling.
It reports on an open-label, uncontrolled study from Hanoi, Vietnam.
The work claims that bone marrow stem cells can help type-II diabetes in some patients.
There is no clear rationale for this approach.
Also, the article reports that it only showed signs of efficacy in patients who met both of these criteria: having diabetes for less than 10 years and BMI of 22 or less. People in Southeast Asia tend to have lower BMI’s than Americans, but still 22 or less is a low BMI for people with type-II diabetes.
What is the point of a journal publishing this kind of study? I don’t get the benefit to the scientific community and there are potential downsides.
Part of what concerns me is that many stem cell clinics are selling the idea of stem cells for diabetes.
That includes in some cases bone marrow stem cells. We’ve seen cases many times where published weak trials are used for promotion by clinics including with cellular approaches to autism.
This kind of work also may give false hope to patients and their families.
Even in studies like https://www.jacc.org/doi/full/10.1016/j.jacc.2009.06.055 and others, the main point which comes up as the most significant conclusion is ‘safety’ and not ‘health improvement’. Although some trials do say that stem cells show positive effects as compared to placebo or other treatment modules, the rationale or understanding of the mechanism is still lacking.
True enough. And there are many ‘journals’ out there that aren’t peer reviewed at all, which further complicates the matter.
Perhaps invite the Author’s to an interview, or discuss your concerns? Good science thrives with lively debate!
Is the study design the cause for concern, or what people (bad clinics/actors) do with said information the concern? MSC’s from a variety of sources are a huge focus of research worldwide. Just like any medical endeavor, not all of them will pan out. But research, both basic and applied, must be done. MSC’s have specifically been looked at for auto-immune diseases, and had success there in some formats (Prochymal, remestemcel-L, etc).
While no ethical scientist wants to promote the unproven clinics plaguing the US and world, we also can’t let that stop vital research into possible treatments for these diseases. If there is a flaw scientifically, that one thing to point out. But we can’t say or infer “I don’t like this line of research because people will use it sell unproven therapies” They are related, but separate things.
Yes, small study design. Yes, odd finding for the subset. But, that’s science for you sometimes. The oddest findings from a data set… sometimes its real, sometimes its an artifact. History is full of this.
@Matt,
Good points.
I believe that a respected journal like SCTM should have higher standards for what it publishes. Here a weak study design and lack of clear rationale, cherry picking subsets to focus on, etc. are the main issue from a publishing perspective. The possible stem cell clinic reverberations are secondary but we’ve seen it happen too often to not at least think about it. The cord blood & other SCTM autism papers that have gotten attention recently raise more direct unproven clinic issues as well as issues related to the Duke/Cryo-Cell push.