Fight Aging!

It is becoming clear that a major factor in the highly variable quality of first generation stem cell therapies has a lot to do with the degree to which cells become senescent when expanded in culture prior to injection. This can vary widely with small differences in culturing technique, even given a similar protocol, or the same team performing the same processes from one batch to the next, absent very rigorous quality control mechanisms of the sort typically not used by clinics in the medical tourism industry. The research community is looking into the use of senolytics to improve outcomes, but it is unclear as to whether this or any of the other possible approaches to minimize cellular senescence in stem cell cultures have yet to be adopted by clinics.

One of the other possible options is the use of photobiomodulation, the use of light to improve mitochondrial function. This may reduce the pace at which cells become senescent meaningfully in cell culture, and perhaps even in tissues, though there is far too little published research on that topic. Even if it isn't that great as a therapy to reduce senescence in people, it may find a use in efforts to ensure that first generation stem cell therapies are less hampered by cellular senescence. Interestingly, the researchers suggest that it may be sufficient to harvest exosomes from stem cells subjected to photobiomodulation and use those to minimize cellular senescence in cultures, though it would seem logistically easier to treat with light.

Photomodulation alleviates cellular senescence of aging adipose-derived stem cells

Mesenchymal stem cells (MSCs) therapies are emerging as a promising approach to therapeutic regeneration. Therapeutic persistence and reduced functional stem cells following cell delivery remain critical hurdles for clinical investigation due to the senescence of freshly isolated cells and extensive in-vitro passage. In this study, cultured adipose-derived stem cells (ASCs) were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, real-time PCR, and Western blot to evaluate the levels related to cellular senescence markers.

The mRNA expression levels of senescence markers were significantly increased in the later passages of ASCs. We show that light activation reduced the expression of senescent genes, and SA-β-Gal in all cells at passages. Moreover, the light-activated ASCs-derived exosomes decrease the expression of senescence, and SA-β-Gal in the later passage cells. We further investigated the photoreceptive effect of Opsin3 (Opn3) in light-activated ASCs. Deletion of Opn3 abolished the differences of light activation in reduced expression of senescent genes, increased Ca2+ influx, and cAMP levels.

We explored the effects of photomodulation on exosome secretion. The concentration of light-treated ASC exosomes represented approximately a fivefold increase compared with non-light-treated ASCs. Light-activated ASC-derived exosomes could represent a new protective paradigm for cellular senescence resulting from in-vitro passaging.