Fruit Compound Called Resveratrol May Strengthen Abilities of Stems Cells of ALS Patients

A natural compound found in certain fruits and vegetables, called resveratrol, may help boost the ability of mesenchymal stem cells taken from amyotrophic lateral sclerosis (ALS) patients to transform into mature nerve cells, researchers in Korea report.

This finding, detailed in a study published in the Journal of Tissue Engineering and Regenerative Medicine, supports the potential of resveratrol to advance patient-derived (autologous) stem cell transplant as a way of treating ALS.

The study is titled “Reduced SIRT1/AMPK in Amyotrophic Lateral Sclerosis Patient‐Derived Mesenchymal Stem Cells can be restored by resveratrol.”

Stem cells are being explored as potential treatments for diseases from cancer to neurodegeneration. These cells can be transformed  into virtually any type of mature cell to potentially restore a biological balance. But their clinical use is limited.

Previous studies have shown that mesenchymal stem cells (MSCs) — isolated from patients’ bone marrow — of ALS patients are lacking in essential abilities of stem cells and show features often associated with aged cells, such as reduced capacity to proliferate.

Researchers at Chosun University in Gwangju evaluated whether resveratrol — because of its known anti-oxidant, anti-inflammatory, and cell protective properties — might improve the capacity of ALS patient-derived MSCs to work as they should.

Resveratrol is commonly found in strongly colored vegetables and fruits — from cranberries, strawberries and blueberries to grape skins, peanuts and soy. But the benefits of consuming large amounts, especially as supplements, is still debated.

The research team compared three samples of bone marrow MSCs collected from healthy individual with samples taken from four ALS patients. Analysis revealed that ALS-derived MSCs had low SIRT1 gene levels, and consistently lower activity in the gene’s the encoded protein (also called SIRT1), which is related to cell longevity. Activation of the AMPK protein was also poor in these ALS-derived cells, which is known to affect cellular energy.

“Recent studies have shown that SIRT1 and AMPK compliment each other for their functional roles in energy metabolism and mitochondrial function,” the researchers wrote.

These findings could, in part, explain the problems seen in ALS-derived MSCs, including their ability to transform into functional mature nerve cells. These proteins have important roles in regulating nerve cell metabolism and age-related degeneration.

Interestingly, resveratrol is known to be an activator of both SIRT1 and AMPK. When the researchers exposed ALS-derived MSCs to resveratrol, a significant rise in the levels and activation of SIRT1 and AMPK were seen.

“The number of neuron-like differentiated [mesenchymal stem] cells, was significantly increased with RSV [resveratrol] treatment as compared with the untreated” MSCs also collected from patients, the study noted.

Researchers also evaluated the levels of some key neural progenitor genes — nestin, Musashi, CD133, and GFAP.

They found that these genes increased in ALS-MSCs upon resveratrol treatment, leading to a higher number of neuron-like differentiated cells as compared to MSCs taken from ALS and not treated with the compound.

“The number of neuron-like differentiated cells, was significantly increased with RSV [resveratrol] treatment as compared with the untreated [cells] … For effective stem cell therapy of neurodegenerative diseases, it is important to recover the neuronal differentiation potency of the stem cells to be used for therapy,” the researchers wrote.

They believe that “resveratrol treatment might be [a] potential strategy for improving therapeutic efficacy of MSCs.”

Further studies with a greater number of samples are needed to confirm these results before this potential treatment might be used in patients, they concluded.