#Stz Nair

[spryfilm]

Trailer: Zack Snyder’s “Rebel Moon” (2023)

[t1np]

Células madres (stem cells, I like the spanish translation more)

Remember that month or two ago when I said I wasn’t hopeful about cure research? Perhaps I spoke too soon. The lab of Matthias Hebrok at UCSF specializes in stem cell research. They have figured out how to better create insulin producing and glucose sensitive Beta-cells from stem cells. The article was published in the journal Nature February 2019, volume 21 and is titled “Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived Beta cells” in case you’re interested. If you dig around you can find a full and free article.

The main difference assessed between the cells they were able to produce and prior beta cell models was the presence of scaffolding that allowed the cells to mature more fully. The consequences of this maturation were significant. The highlights as I see them are below:

They definitively prove that the issue of clustering the endocrine cells leads to more fully matured cells or what they call in the article enhanced beta cells or eBCs. They prove this on a number of levels: through testing glucose sensitivity, I.e: these cells produce insulin at high glucose concentrations and stop at low levels. The also prove this by looking at genetic markers of mature beta cells. The genetic markers of mature cells are present in the eBCs. There are also smaller amounts of so called “disallowed genes” that interfere with cells ability to produce/decrease insulin in response to glucose levels. Cheers to the Aggrewells-400s they used to create happy little beta cell houses.

The eBC cells are functional after transplantation within 3 days! Up to now the beta cells formed from stem cells have required 2-6 weeks following transplantation to become functional. These are far more functional in insulin production and faster than all other man-made beta cells. Boom!

When tested in mice with diabetes induced by treatment with STZ (streptozotocin) the eBC stem cell grafts were able to keep the mice blood sugars under control. The blood sugars of the group of mice without the grafts unsurprisingly, went super high.

The grafts were happy and healthy in the mice bodies after 8 months. Up to now beta stem cell grafts have turned into messy disorganized blobs after just 3 months. The eBCs more closely resemble functional Beta cell tissue.

So the eBC grafts are better, faster acting and lasting than all others to date in an in-vivo model.

That is GD exciting.

Some things I’m concerned about

The potential of growing cancerous tumors instead of beta cells d/t incomplete filtering of cells. Stem cells, due to their very magical nature can turn into all sorts of things. The stakes are then raised when these cells are filtered for a very specific purpose. That filtering better be GOOOOOOD.  

When will this get approved, especially in the US? The only current FDA approved use of stem cells are hematopoietic progenitor cells to treat certain cancers and blood disorders. These cells have been studied for therapy for roughly 50 years. As much hype there has been around stem cells, as therapy, it’s still in early stages. The article discussed an 8 month study of efficacy but we’ll need more than that, in more than mice for clinical trials to begin. Which is just step one of the process. Given the cost of type 1 in the United States it could possibly be moved along faster.

In the article they discuss the 2 phases of insulin production. The first being the immediate insulin release directly from beta cell stores that happens when we eat. Apparently eBCs produce lower levels of insulin than adult beta cells. The second phase of insulin delivery in eBCs is also not sustained. Reading the article I was unclear if this was a good or bad thing but I imagine that the second release is also important for blood sugar regulation. These glitches I’m less worried about than the former two but it does give me some pause. Though I guess beta cells on the struggle bus are better than what I’ve currently got going on.

So that’s my summary but check it out for yourself!

https://www.nature.com/articles/s41556-018-0271-4

I take some joy in the fact that just like you can’t manage diabetes on your own, Beta cells can’t get where they’re going without being clustered together and snuggling. Cheers to getting support, holding on to hope and giving the deuces to T1d!

Also, cheers to all these people who hang out long lonely hours in a lab to figure things out and babysit fussy cells and make magic like this happen. Specially the middle authors cause we know you did most of the grunt work:

Gopika G. Nair, Jennifer S. Liu, Holger A. Russ, Stella Tran, Michael S. Saxton, Richard Chen, Charity Juang, Mei-lan Li, Vinh Q. Nguyen, Simone Giacometti, Sapna Puri, Yuan Xing, Yong Wang, Gregory L. Szot, Jose Oberholzer, Anil Bhushan & Matthias Hebrok

References: Nair, G., et al. Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived Beta cells. Nature, Cell Biology 21, 263-274 (2019). 

[spryfilm]

Trailer: Zack Snyder’s “Rebel Moon: Part One” (2023)