16 replies to this topic

[GabrielPaparella]

I saw on the SENS website news about a senescent T-cell scrubber working successfully, which is great news.

http://sens.org/rc/projects/scrubber1

A core theory of SENS, ImmunoSENS, posits that the removal of senescent T-cells from the blood could highly increase the ratio of working to senescent T-cells and in the process, rejuvenate the immune response of the subject. Senescent T-cells are characterized by the presence of a protein called KLRG1 that increases with age. The goal was to single out T-cells expressing this protein and remove them.

One of the projects that was completed in 2009 at the SENSF-RC was the first scrubber. This was an experiment to provide a proof of concept for the initial stages of ImmunoSENS. Specifically, to determine if the removal of senescent T-cells from the systems of middle-aged subjects could be automated. The primary aims: speed and stress minimization to the subject.

The technique for accomplishing this was magnetic cell sorting. Micron-sized particles coated with streptavidin were conjugated with anti-KLRG1 antibodies. We created a robot that could selectively remove senescent t-cells by means of a magnet.

The model organisms selected for this project were mice. Each mouse was fitted with a jugular catheter. Prior to application of the machine each mouse had its blood tested with a flow cytometer to determine the ratio of cell types it possessed. The device was then attached to the mouse's catheter and in operation performed the following steps ten times:

1) removed 280uL of blood.
2) inversion stirred the blood with the paramagnetic anti-KLRG1 particles.
3) introduced a strong magnetic field to the blood sequestering the particles and senescent T-cells.
4) infused the cleansed blood back into the mouse
5) allowed time for the cleansed blood to homogeneously mix with the mouse's blood.

Following the operation each mouse was once again given flow cytometer readings. The results definitively proved that the machine removed the vast majority of the selected cells.

They created a robot, people!

It doesn't say the mass of the mouse in question, but if it was average then by my calculation 280uL is 20% of its blood volume, so doing this 10 times, provided step 5, would be the same as performing it on 90% of the mouse's blood.

[eternaltraveler]

yep, thats what we did.

The question of whether or not this would provide any clinical benefit is a question that has not been answered.

here is the sens4 presentation I gave and paper

http://75.126.26.34/...em&g2_itemId=34
http://www.lieberton...9/rej.2009.0964

[Florin]

The question of whether or not this would provide any clinical benefit is a question that has not been answered.

How could this question be answered? If there's any, currently-recognized disease that would benefit from this procedure, it seems that it would be pretty straight-forward to test this procedure against that disease.

[John Schloendorn]

Not sure what the FDA would say to that, but perhaps vaccine response rate in the elderly might be a first thing to look at?
It's a big problem, first not responding to the flu vaccine, and then dying from the flu.

[Elus]

Fantastic work. Can you use a similar technique to perform an extraction of other components which might be deleterious to mice/humans?

One example might be also be binding goldnanoparticles to lipofuscin and applying a laser which causes the nanoparticles to resonant and generate localized ROS via 5-ALA molecule bound to its surface (This is what my work at Stevens Institute involved, except with cancer cells). The downside to this is that the localized ROS might not be easy to control and would cause even more damage then they clean up, but it might be work a shot.

Or perhaps you can induce temporary electroporation in certain cells which have nanoparticles bound to lipofuscin inside the cells, and then apply a magnetic field to the cells, allowing for an extraction of lipofuscin. If the composition of lipofuscin is indistinguishable from other types of important cellular components, this technique might accidentally extract the wrong thing, so one would have to be cautious with that. Also, electroporation might accidentally allow certain things to enter the cells which wouldn't have entered normally, which would be problematic O_o LOL

I'm just throwing ideas left and right :P

Nice job, guys!

Edited by Elus, 01 October 2010 - 05:48 AM.

[eternaltraveler]

The question of whether or not this would provide any clinical benefit is a question that has not been answered.

How could this question be answered? If there's any, currently-recognized disease that would benefit from this procedure, it seems that it would be pretty straight-forward to test this procedure against that disease.

Well, first, in order for a question to be answered it has to be asked.

You could test vaccine response in the elderly following senescent t cell removal or any other number of things. Probably with monkeys first. It's pretty straight forward.

[Florin]

You could test vaccine response in the elderly following senescent t cell removal or any other number of things. Probably with monkeys first. It's pretty straight forward.

Are there any plans to test this procedure either by determining if vaccine response is affected as you've mentioned or in another way? If it's too expensive for the SENSF to conduct this kind of test, perhaps a study in mice might be less expensive or a mainstream org might be interested in funding a more expensive monkey or human study.

Edited by Florin Clapa, 01 October 2010 - 05:51 PM.

[Florin]

One example might be also be binding goldnanoparticles to lipofuscin and applying a laser which causes the nanoparticles to resonant and generate localized ROS via 5-ALA molecule bound to its surface (This is what my work at Stevens Institute involved, except with cancer cells). The downside to this is that the localized ROS might not be easy to control and would cause even more damage then they clean up, but it might be work a shot.

A recent study of a nanoparticle/laser approach similar to what you've mentioned combined with adult stem cells reduces atherosclerotic lesions in pigs by 57% and supposedly "rejuvenate[s] the arteries."

[GabrielPaparella]

HIV Infection as a Model of Accelerated Immunosenescence

The scrubber could also be used as a treatment for immunosenescence-related decreased immune response in HIV infected people.

In a human population that is in the advanced stages of fighting HIV, I suspect we could expect the benefits of the scrubber to show themselves to be statistically significant or not rather quickly. Also, this has the advantage of being indisputably a treatment for a disease and not aging, from a regulatory perspective.

[niner]

Fantastic work. Can you use a similar technique to perform an extraction of other components which might be deleterious to mice/humans?

I agree. In principle, it could be used to remove any object or molecule in the bloodstream that you could specifically tag with an antibody. I'm not so sure about pulling out a sub-cellular component, or pulling out a cell from a solid tissue. I think those problems would require a different approach. Such problems probably will succumb to related nanotech methods, though. When we think about nanotech fixes for aging, we should be thinking about things on this level, not about nanobots. This stuff works today. Nanobots may or may not exist at some unspecified point in the future, and may or may not work as we imagine.

[eternaltraveler]

The scrubber could also be used as a treatment for immunosenescence-related decreased immune response in HIV infected people.

maybe as some kind of adjuvant treatment. But I really doubt it would do much of anything for HIV. A better approach would be to repopulate cd4s with ones that have been modified to be more resistant to infection with CCR5-Δ32.

[eternaltraveler]

principle, it could be used to remove any object or molecule in the bloodstream that you could specifically tag with an antibody

indeed. There are many useful targets in the blood. If antibodies weren't so expensive this could work better for purifying our blood than many of our endogenous systems.

[maxwatt]

principle, it could be used to remove any object or molecule in the bloodstream that you could specifically tag with an antibody

indeed. There are many useful targets in the blood. If antibodies weren't so expensive this could work better for purifying our blood than many of our endogenous systems.

Increased demand eventually lowers price, absent some absolute constrain on production.

[Link]

Does anybody know if anything is happening with this project? It seemed very promising when i first read about it but there hasn't anything new in the last few years.

[Florin]

Back in December 2012, it was "sitting on the shelf" according to Aubrey (at about 9 minutes into the interview). I suspect the reason is lack of funding. Anyway, there has been no other news about it.

Edited by Florin Clapa, 04 January 2014 - 06:39 AM.

[Mind]

I am pretty sure Justin Rebo has been working on this lately. I'll see if he can chime in.

[eternaltraveler]

We are making a next generation device now and will be testing whether or not this approach improves response to infection and vaccination. Will be happy to chime in once this is done. Probably within the next year