SENS Research Foundation on Synergies between Senolysis and Stem Cell Therapy
In their latest newsletter, the SENS Research Foundation leadership noted one of their more recent programs, focused on identifying synergies between senolytic therapies to remove senescent cells and stem cell therapies intended to augment regeneration. It is possible that senolytic treatment could help make the aged tissue environment less hostile, enabling transplanted cells to better aid regeneration and tissue maintenance. This is a comparatively straightforward hypothesis to test in animal studies: all of the necessary tools already exist, and just need to be combined. Finding an improvement would likely speed the adoption of first generation senolytic therapies, such as the dasatinib and quercetin combination, by encouraging their use in the sizable stem cell medicine community.
The accumulation of damaged/senescent cells in the body with time is a hallmark of aging. These cells are believed to play a key role in the onset and/or progression of various aging-associated diseases. More generally, the decreased regenerative ability of transplanted stem cells in older recipients may also be partly attributable to the presence of a high level of senescent cells.
Many factors produced by senescent cells - including proinflammatory cytokines, profibrotic molecules, and damaging agents such as labile iron and reactive aldehydes - are known to disrupt the function of normal cells and cause organ function to decline. The hostile environment created by senescent cells is likely to impair the ability of transplanted stem cells to home in on target tissues, mature, and restore tissue function. Therefore, prior removal of senescent cells will likely enhance the effectiveness of stem cell transplantation therapies.
In recent years, two major observations in the longevity field have been made: (a) The use of senolytics to remove senescent cells significantly improved health and lifespan in mice and as might be expected, this approach enhanced the repopulation ability of endogenous stem cells (b) stem cell transplantation has demonstrated beneficial effects in reducing aging-associated functional decline in both mice and humans, and extended lifespans in mice. Our SenoStem project will test the hypothesis that prior removal of senescent cells by senolytics will create a more favorable niche for stem cells to engraft, and thus enhance their regenerative effect in older recipients. The overall aim is to determine whether these two different lifespan-extending interventions can act synergistically.
Link: https://www.sens.org/exploring-synergies-between-senolysis-and-stem-cell-therapy/
While they are at it, check to see if a tiny bit of epigenetic reprogramming / resetting would do the same. Though, I suppose we are closer to senolytic treatments than we are to epiregen.
I am surprised there are so few senolytic studies since some of them can be done pretty cheap with small groups of patients.
Just from the top of my head for a single dose treatment.
Back pain management.
Controlling blood sugar for diabetes II
Recovering after heart attack
Cholesterol management.
It seems that mitochonria transfer from stem cells to T regulatory cells may explain part of the anti inflammatory effect of stem cells:
Mesenchymal stem cells transfer mitochondria to allogeneic Tregs in an HLA-dependent manner improving their immunosuppressive activity (2022):
https://www.nature.com/articles/s41467-022-28338-0
I've always thought it made sense to combine senescent cell clearance with a top up of young stem cells. (Out with the old in with the new, so to speak). I could imagine a time where you go on a "rejuvination holiday" to some resort. On the first day they extract some high quality stem cells and put them in some sort of replicator. At the same time they put you on a senolytic program to remove senescent cells. Then you can relax for a while or go home and come back once your senescent cells have died off and your new cells are ready for infusion. Sounds great right?
Synergies? LOL!
They didn't even show that either of those two have meanlingful and lasting efffects in humans.
prior removal of senescent cells will enhance the effectiveness of stem cell transplantation therapies.
but will the SenoStem project demonstrate
simultaneous (at the same time) removal of senescent cells will likely enhance the effectiveness of stem cell transplantation therapies.
Also will the SenoStem project demonstrate the removal of senescent cells after stem cell transplantation therapies? Do senolytic therapies post stem cell transplantation therapies disrupt the treatment?