RB2015 — Helen M. Blau: Rejuvenation of Aged Muscle Stem Cell Population
Day 2, August 20
Continuing in my live blogging series from the Rejuvenation Biotechnology 2015 conference is Dr. Helen M Blau’s auspicious talk on restoring muscle function in the hind limbs of aged mice to the level of young mice using stem cells and hydrogel.
Dr. Blau Professor of Microbiology and Immunology at Stanford University Medical School, where she has been a faculty member since 1978. At Stanford she heads the Baxter Laboratory for Stem Cell Biologyand is a Member of the Institute for Stem Cell Biology and Regenerative Medicine and Faculty Affiliate of both Bio-X and the Stanford Cardiovascular Institute.
Why do we care about muscle stem cells?
We already have stem cells that can be recruited to repair damaged tissue: muscle stem cells.
These are dedicated stem cells. They won’t become bone or cartilage. This restricted potential is an advantage to other stem cells, which if receive the wrong signal, can differentiate into bone. There are also no tumors of muscle. These cells are not at risk of giving rise to cancer.
Hematopietic stem cells are another example of cells dedicated to one function (blood).
The Luciferase assay enables detecting when a single cell was injected and expanded in the mouse. This worked in 3 out of 74 mice.
The bioluminescence signal plateaus after day 10. This proves they don’t produce cancer. But they no longer retain their stem cell state. 90% of the cells are not regenerating very well.
Klass Magnuson is an AI researcher who developed algorithms to track cells that won international awards.
Nothing sticks to hydroels (serums, proteins). This material is great because we can control rigidity with tunable parameters. It’s also transparent — great for microscopy.
The team transplanted 100 cells into irradiated hind limbs of a mouse, so they can compete with native cells for the niche.
Do the stem cells change in the aged individual, and if so, can we overcome the changes?
We see increase in senescence markers. One particular drug triggered increase in division. Doesn’t necessarily mean rejuventation, but the cells were dividing a lot more often.
The hydrogel and the SB drug synergize to restore function in aged mice.
To track cell division automatically, we need AI algorithms. The task is simple for the human eye, but not for computers yet.
1/3 of the residual cells that are functional in aged animals, are expanded by drug targeting. This is great, because we don’t want old cells, with chromosomal aberrations, to expand.
Stem cells home in to their native niche, so they constitute a reservoir.
Scott Delp has developed an in-vivo muscle function assay. The team was excited to find that
strength in aged mice had been restored to that of the young
Q&A
Drug candidates have been identified, work in progress.
No comparison of exercised mice vs. mice with the transplant.
The stem cells do last. They go back to the niche, reconstitute the reservoir, and give rise to more stem cells.
Haven’t looked at lifespan.
