Fat-Derived Mesenchymal Stem Cells Prevent the Onset of Alzheimer’s Disease in Mice

According to a study by researchers at the RNL Bio Stem Cell Technology Institute and the Seoul National University in Seoul, South Korea, intravenous stem cells infusions can improve the symptoms of Alzheimer’s disease patients and might even prevent Alzheimer’s disease altogether.

Mesenchymal stem cells from human fat tissues (known as adMSCs for adipose-derived mesenchymal stem cells) can be infused into the brains of laboratory animals that have been manipulated so that they acquire a form of Alzheimer’s disease (AD). Then these cells are intravenously infused, the brains of these animals undergo some regeneration.

Researchers injected adMSCs into the tail vein of APPswe Tg2576 mutant mice. These mice express a mutant form of the APP gene that is found in Swedish people who have a very aggressive form of AD. By 11-13 months of age, these mice show a 14-fold increase in the toxic form of amyloid protein called Aß (1-42/43) over normal mice by 2-8 months of age. These elevated Aß levels cause deposition of amyloid deposits in various portions of the brain (the frontal, temporal, and entorhinal cortex (EC), hippocampus, presubiculum, subiculum, and cerebellum, for the interested).

The adMSCs circulated throughout the body and they passed through the blood-brain barrier to home to the site of injury. This is remarkable finding because it was thought that stem cells could not pass through the blood-brain barrier. The researchers labeled their cells with a fluorescent protein and the presence of fluorescence in the brain confirmed that the stem cells do enter the central nervous system.

These APPswe Tg2576 mice had adMSCs infused into them every two weeks from their 3rd month of life until their 10th month. At this time, the mice that had received the stem cell infusions showed greater abilities to remember, learn and did not show AD behavioral symptoms, whereas their control counterparts that received placebo injections had learning and memory disabilities and also showed other AD behavioral symptoms.

When the research teams asked why the infused stem cells improved the neurological characteristics of APPswe Tg2576 mice, they discovered that the stem cell-infused mice had much less inflammation in their brains and also far few inflammation-associated chemicals in their brains. IL-10, for example, is a chemical that protects neurons and quells inflammation in the brain, and IL-10 levels in the brains of stem cell-infused mice were much higher than in the control mice.

Finally, when the brains of these mice were examined at the tissue level, the result was even more astounding; the infused adMSCs prevented the formation of amyloid plaques that are so common in the brains of AD patients. In fact, amyloid protein levels were lower in stem cell-infused mice. It turns out that the adMSCs stimulate the production of a protein called neprilysin, which acts as a pair of amyloid protein scissors. Neprilysin degrades amyloid protein and prevents the formation of the large pools of toxic amyloid pools that kill neurons and tip-off a cascade of dying cells in the brain.

The therapeutic benefits of adMSCs did not stop there. They also induced surviving neurons to divide and differentiate into neurons that aid learning and memory. The chemicals secreted by the adMSCs also stabilized the specialized connections between neurons, known as synapses.

Thus fat-derived MSCs provided preventative and curative functions for AD mice, and hopefully, this pre-clinical research will lead to human clinical trials for AD patients.