Hi, Jeffrey Huo, I'm being lazy and not reading the original papers. What's the detailed info? Is this legit?
Hi, Jeffrey Huo, I'm being lazy and not reading the original papers. What's the detailed info? Is this legit?
https://www.nature.com/news/lab-grown-blood-stem-cells-produced-at-last-1.22000
https://www.nature.com/news/lab-grown-blood-stem-cells-produced-at-last-1.22000
https://www.nature.com/news/lab-grown-blood-stem-cells-produced-at-last-1.22000
https://www.nature.com/news/lab-grown-blood-stem-cells-produced-at-last-1.22000
I have to scrutinize the paper in depth, but the field as a whole - and George Daley's lab in particular - have been painstakingly getting closer and closer and closer to achieving the goal of making a real hematopoetic stem cell from scratch for twenty years. A whole succession of really beautiful papers has gotten, one tiny step at a time, close to the goal.
ReplyDeleteThe canonical definition is making something in the lab which, when trasplanted, makes the entire repertoire of blood cells; and critically, when transplanted from that first recipient into another successfully does the same thing again. Maybe Daley has finally done it? I have to read the paper with a magnifying lens.
It's only a matter of time before somebody finally gets it; maybe this is it. :-)
Yes, well, devil's always in the details. :)
ReplyDelete...so, looking at the paper in a bit more depth, my first thought is that, well, it is a step forward, and that is important. Nature worthy, even. Not sure how --big-- of a step forward, and it's certainly -still a long way from the real thing. But nobody was expecting to get there in a single bound.
ReplyDelete(In fairness, the whole field of pluripotent stem cells was born out of a holy-s##t! moment of incredible discovery that went from "that's impossible" to "holy s##t, everyone can do this", but then, that's why Yamanaka was a Nobel laureate not even a decade after his discovery.)
Their latest paper attempts to build from their prior major paper (Doulatov 2013, Cell). In the gradually advancing progression of progress, each generation of candidate hematopoetic stem cells is capable of doing more than each previous. To expand on what I noted above: a true hematopoetic stem cell (like the ones in our bone marrow) can make all parts of the blood. Which is a pretty complex thing. Red cells, white cells, platelets, etc. etc etc. And not just making them, but fully functional, adult (not merely fetal) versions of all of the above.
The key major box the authors are attempting to argue they've now checked off is showing that their latest generation artificial hematopoetic stem cells may be repeat transplantable. This is an important step, because one of the most important things that a hematopoietic stem cell can do, is keep making more of themselves that can keep doing the job. That's how we keep being able to make blood across our entire lifetimes, for example, and likewise why it is possible to take bone marrow from one person and transplant it into the next. Older generations of candidate artificical hematopoetic stem cells were essentially one-time-use only - they go in, differentiate into new blood, but didn't retain the capacity to re-seed; suggesting that the original hematopoetic stem cells either couldn't replicate and renew, or they never quite got that far back in the first place.
In this latest paper, Daley and friends claim to show data that shows that if they put their next-gen artificial blood stem cells into a mouse, the mouse then generates new blood that roughly has all the components of true blood. They then argue that if they take the new marrow the first mouse has made, they can put that new marrow from the first mouse, put it into a second mouse, and again grow new blood from scratch, with all the components of a normal blood stream. But...
If one looks at the actual data, yes, technically speaking the new blood has all major lineages, as measured by one specific assay. But it looks to me like they barely have red cells (erythroids), for example. Which begs the question about whether that's a "real" success. It sure as heck isn't robust.
But that's fair - this is a really hard thing to do, and even just getting this far is, again, not unreasonable as a Nature-level discovery. They claim that the red cells that they do make - even if there's not many of them - appear to be capable of making red cells that make mature hemoglobin. From embryonic development to birth, our red blood cells move through a series of hemoglobins, from embryonic to fetal to adult. Earlier RBCs weren't able to make red cells that fully made that journey; it appears at first blush these newest hematopoetic stem cells have their s##t together enough to go most of the way, which is also not common.
So all in all, is the problem solved? I don't think so. Is it a step forward? I think it's fair to say yes. Again, this is only a quick read, but there's my thoughts. :)
That's kinda what I figured. Major step forward, but not what the reporting tries to imply.
ReplyDelete