Human MSC extend life span in rats

by Alexey Bersenev on August 29, 2015 · 0 comments

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The recent study, published in Stem Cells TM, demonstrates that infusions of mesenchymal stromal cells (MSC) can impact aging and longevity. A group of Korean researchers used human MSCs in rats to “rejuvenate their brain” and to show possibility of life span extension. This is the second study, which shows increase in life span of experimental animal by administration of MSC. The first study was published in 2012 and it was done in mice. Unlike 2012 study, Dajeong Kim used xenotransplantation model, where human MSCs were infused into rats. Different experimental models led to quite similar result – significant animal life span extension and rejuvenating effects in tissues.

There are few surprising findings in this new Korean study. First, the life span extension in experimental rats was very impressive ~23-31%. This number is comparable to calorie restriction and greater than Rapamycin effects on longevity. Based on many published longevity studies, it is very very hard to achieve ~20-30% life extension rate. Second, it worked in xenogenic transplantation system without immunosuppression or/ and host pre-conditioning. One may expect rapid rejection of human cells by competent rat immune system, but seem like it was not the case. Repetitive monthly infusions of 1 million human MSC since young age, may induce immune tolerance. Third, brain rejuvenation effects were quite similar between 2 types of MSCsm used in the study – amniotic membrane-derived and adipose tissue-derived. However, adipose-derived MSC were superior in “life span-extending capacity”. Fourth, rejuvenating metabolic effects of human MSCs in rat brain were very impressive. Importantly, these effects were due to “transdifferentiation” of MSC in neural-like cells:

Transplanted cells were found in the brain, predominantly in the cortex and hippocampus, and differentiated into ChAT- positive neurons…
Repeated transplantation of AMMSCs or ADMSCs markedly recovered the decreased lev- els of MAP2 and cholinergic and dopaminergic nervous system markers in aged rats, indicative of a structural restoration of brain integrity, although the MAP2 level might be a total amount added by the transplanted stem cells following differentiation into MAP2-positive neurons. The improvements of cognitive and motor functions by stem cell transplantation might be due to the increased ACh levels in the brain and muscles originated not only from the transplanted stem cells but also from restored host cholinergic neurons.

The other rejuvenating effects of MSC in tissues included “increase microvessel density and muscle mass and enhance antioxidative capacity”. Increasing of muscle mass led to “enhanced stamina in forced swimming” test in aged animals.

Interestingly, both – current and 2012 studies used 1 million MSCs dose, infused intravenously. However, in 2012 study it was one shot in pre-conditioned by radiation mice, but current study utilized monthly infusions in “normal rats”. In both studies cells were expanded in culture and expressed “classical” MSC markers.

The results of this study look impressive to me! It seems strange that the study was covered very poorly in the media. I’d encourage you to read it critically and discuss it here or on any other social platform.

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