Friday, March 2, 2012

From stem cell to tissue: mechanism discovered

Stem cells are classified as cells that have the capability to morph themselves in various tissues, a process known as differentiation. Almost every organ has a supply of 'adult' stem cells that have committed to a certain lineage, but still have the flexibility, or plasticity, to turn into various cell types. The famous embryonic stem cells, however, are the most plastic of them all. They have the capability to turn into anything, which makes them of great interest to scientists to develop new therapies for tissue regeneration. So far, not much was known about what makes a stem cell stay in its 'primitive' shape, and which signals make it divide or differentiate into a cell of a specific tissue. Scientists from the University of Georgia claim to have made a discovery that explains this.

One of the key signals in primitive cells is Wnt. It plays an essential role in development from fertilization of the egg to forming a fully-fledged organism. It is method of action is incredibly complex, but when it comes to stem cells scientists have long thought that Wnt signalling must be absent to allow a primitive cell to keep renewing itself instead of specializing. However, scientists found that when it is present in low quantities, stem cell character is kept. They also discovered that Wnt actually needs to be present in higher quantities before a stem cell gives up its primitive character.

Timing and collaboration
The switch from stem cell to specialized tissue cell is further complicated by actions of various other molecules, that amplify each other, eventually yo tip the balance towards specializing. At the University of Georgia, they found that timing and concentration are of vital importance to govern the switch from a stem cell to a more specialized cell. It is actually more complex than switching a signal on and off, as the picture below shows. The essence of it is that Wnt lies at the foundation of it all, in collaboration with other molecules.
A rather complicated balance. P13K/Akt is the switch that makes Wnt signalling tip the balance to differentiation. A lot of other molecules complicate this process because they all communicate with each other. The comic shows how a pluripotent cell (a stem cell) turns into mesendoderm (a specific cellular lineage), on its way to specialization.

Replenishing tissues
Adult stem cells, that have committed to a certain organ, are extremely important in providing the body with new cells to take over from old ones. Normally, every few months an organ is completely replaced by new cells. Specialized cell types are extremely useful to carry out a specific function, but they normally do not live very long. That is why the body needs a constant turn over of new cells, which branch off of stem cells. Daughter cells are being created which are sent on their way by differentiating to specialized tissue cells. Meanwhile, the original stem cell stays in its primitive shape, to give birth to more daughter cells.

Clinical use
Stem cells are of great interest to scientists because of their therapeutic potential. In some cases, the body is unable to repair damage, such as after a stroke or heart attack. Artificial tissue regeneration by injecting stem cells that turn into specialized tissue and integrate with the existing cells is the hallmark of what scientists have been trying to develop in the last two decades. It has not yet yielded many usable therapies, but discovering the biological mechanisms underlying stem cell renewal and differentiation will probably help us to fine-tune stem cell-based treatment and increase its potency.

How Wnt and its associates turn cells with a 'blank page' into something that carries out a specific function is an important mechanism in embryology. Many organisms are built around the same body plan, and share many of these molecules with us. When considering the fact that almost all multicellular organisms are built from a single fertilized egg that keeps on dividing and sprouts cells that commit themselves to specific cellular lineages creating organs and tissues, it is clear that the newly discovered Wnt pathway stands at the foundation of life. The discovery increases our knowledge about the essence of life.

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