11 June 2013

Stress-resistant pluripotent stem cells from adipose tissue

The new hope of regenerative medicine

LifeSciencesToday based on UCLA Newsroom:
Fat chance: Scientists unexpectedly discover stress-resistant stem cells in adipose tissueScientists of the Department of Obstetrics and Gynecology at the University of California, Los Angeles (UCLA) have identified a population of human pluripotent stem cells resistant to cellular stress, capable of differentiating into almost any type of body cells without genetic modification.

The population is located in adipose tissue and is easily accessible.

The cells, called multilinear stress-resistant stem cells of adipose tissue (Multi-lineage Stress-Enduring stem cells from adipose tissue, Muse–AT stem cells), were discovered due to a "lucky" case - a breakdown of laboratory equipment, which destroyed all experimental stem cells with the exception of Muse-AT cells. As it turned out during further experiments, Muse-AT cells are not only able to survive under extreme stress, but are also activated by it. The results of a two-year study by American scientists are published in the peer-reviewed scientific journal PLoS ONE (Awakened by Cellular Stress: Isolation and Characterization of a Novel Population of Pluripotent Stem Cells Derived from Human Adipose Tissue).

Pluripotent Muse-AT cells isolated from adipose tissue removed during liposuction express many markers of embryonic stem cells and are able to differentiate into muscle, bone, fat cells, cardiomyocytes, neurons and hepatocytes. The genetic characteristics of the cells differentiated from Muse-AT confirm their specialized functions, as well as the ability to regenerate tissues during transplantation after being "awakened" by stress (photo: UCLA).Pluripotent cells isolated from adipose tissue removed during liposuction express many markers of embryonic stem cells and are able to differentiate into muscle, bone and adipose tissue cells, cardiomyocytes, neurons and hepatocytes.

"This population of adipose tissue cells is at rest until it is exposed to very harsh conditions. These cells have the ability to survive in conditions in which only cancer cells can normally live," says senior author Gregorio Chazenbalk, PhD, associate researcher at the UCLA Department of Obstetrics and Gynecology. "After in-depth study and clinical trials, they can become the basis of a revolutionary method of treating many diseases, including heart disease and stroke, as well as repairing damaged nerves and other tissues."

Purification and isolation of Muse-AT cells does not require the use of cell sorters or other specialized high-tech devices. They are able to grow either in suspension, forming cellular spheres, or attached to a substrate. In the latter case, cellular aggregates are formed very similar to embryoid bodies formed from human embryonic stem cells.

"We were able to isolate these cells using a simple and effective method. From the moment the adipose tissue is obtained, the entire procedure takes about six hours," continues Dr. Chazenbalk, a researcher at the Center for Regenerative Medicine and Stem Cell Research Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. "This study offers an interesting new source of adipose tissue stem cells with pluripotent properties, as well as a new way to isolate them quickly. In addition, these cells appear to be more primitive than conventional fat stem cells, making them a potentially more suitable source for use in regenerative medicine."

Currently, the two main sources of pluripotent cells are embryonic stem cells and induced pluripotent stem cells – skin cells transformed into cells close to embryonic. However, cells of both these types can exhibit an uncontrolled ability to differentiate and proliferate, which leads to the formation of undesirable tumors – the so-called teratomas. According to Dr. Chazenbalk, significant progress in solving this problem has not yet been achieved.

Muse cells were originally discovered by a group from Tokohu University, Japan, and were obtained not from fat, but from bone marrow and skin. In animal models, Japanese scientists have shown that Muse cells do not form a teratome. Further studies are needed to confirm that the population of Muse-AT cells isolated at UCLA also avoids the formation of these tumors.

Scheme of isolation and activation of Muse-AT cells by cellular stress (A). Muse-AT cells can grow in suspension, forming both spheres or clusters of cells and individual cells (shown by red arrows) (C), as well as attach to the substrate and form cellular aggregates (D). In both cases, the Muse-AT cell reaches a diameter of about 10 microns, and cell clusters - 50 microns, which is comparable to the size of stem cells capable of proliferation (Fig. PLoS ONE).According to Dr. Chazenbalk, in addition to the potential practical use as a source of stem cells in regenerative medicine, Muse-AT cells will deepen our understanding of cancer cells - the only other cell type demonstrating such high resistance to stress.

In the near future, Chazenbalk and his colleagues plan to conduct experiments with Muse-AT cells to regenerate damaged or dysfunctional tissues in animal models and investigate how effectively they grow and perform their functions in a living organism. This will make it possible to assess their clinical potential.

According to Chazenbalk and his colleagues, since lipoaspiration is a safe and non-invasive procedure, and a simple and at the same time very effective purification technology is required to isolate Muse-AT cells, they can become an ideal source of pluripotent, close to stem cells and have a decisive impact on the development of regenerative medicine.

Portal "Eternal youth" http://vechnayamolodost.ru11.06.2013

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