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MSCs: An Effective Remedy for Aging?

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Review of “Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats” from Stem Cells Translational Medicine by Stuart P. Atkinson

Creaks, clicks, groans, and moans…….aging brings them all, but what if there was a means to delay this impending doom?! Well, read on, as researchers from the laboratories of Yun-Bae Kim and Jeong Chan Ra have this week reported that monthly intravenous treatments of mesenchymal stem cells from amniotic membrane (AMMSCs) or adipose tissue (ADMSCs) have the ability to rejuvenate naturally aging rats [1]! 

The group found that intravenous transplantation of 1 million MSCs every month into aged immunocompetent F344 rats (10 months) inhibited the decrease in ease of movement, coordination, and stamina and also inhibited the loss of learning and memory function normally associated with aging. This correlated to an increase in levels of the neurotransmitter acetylcholine (ACh) in the brain and muscle, but also to a 20-30% extension in lifespan without an increase in the incidence of tumor growth.

So where are these cells going and what affects are they having in the aging rats? By tracking human cells using an antibody recognizing human mitochondria, the study found that MSCs mainly homed to the cortex of the brain where they mainly differentiated into choline acetyltransferase (ChAT)-positive cholinergic neurons. The authors also noted that MSC-treatment enhanced the number of cycling Nestin-positive stem cells, and the overall number of stem cells, indicative of enhanced neurogenesis. This reversed age-related deterioration of both the cholinergic and dopaminergic nervous systems, and an enhanced level of blood vessel formation was also noted. This pro-angiogenic effect was also observed in the muscles, where it was accompanied by an increase in muscle mass, and reduced oxidative stress and associated tissue injury throughout the body.

While a positive effect of MSC transplantation has been observed a mouse model of accelerated aging [2], this is the first report in a normal animal model. Additionally, the study did not see any evidence of immune rejection, further enhancing the potential for MSCs in anti-aging therapies. The study did however use low passage number primary MSCs, and this may represent a bottleneck for widespread use at larger cell concentrations which may be required for larger animal/human testing. Additionally, application of autologous MSCs will also carry some additional problems, such as the potential for loss of function after long-term storage (such as for amniotic membrane MSCs) or potential loss of function of the MSCs from elderly patients or long-term in vitro culture. 

References

  1. Kim D, Kyung J, Park D, et al. Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats. Stem Cells Transl Med 2015;4:1144-1154.
  2. Lavasani M, Robinson AR, Lu A, et al. Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun 2012;3:608.