Sickle cell mice cured by stem cells reprogrammed from their own tails

Blogging on Peer-Reviewed ResearchSickle cell mice cured by stem cells reprogrammed from their own tailsStem cells have long been hyped as the shiny future of medicine. Their ability to produce to every type of cell in the body provided hope for treating diseases from Alzheimer’s, to Parkinson’s to stroke, by providing a ready supply of replacement cells. Despite years of slow progress, we are now tantalisingly close to turning this hype into reality and a new study suggests that the dawn of promised stem cell treatments is getting closer.

For the first time, scientists have cured mice of a genetic disorder called sickle cell anaemia using personalised stem cells reprogrammed from cells in their tails. The study is a powerful ‘proof-of-principle’ that reprogrammed stem cells could one day fulfil their potential in fighting human disease.

The personal touch is of the utmost importance. It’s no good just giving someone any old stem cells. Genetic differences between the donor and recipient could cause problems in the long-term and trigger attack and rejection from the hosts’ immune system in the short-term. The trick is to convert a patient’s own cells into personalised stem cells for their own private use.

Last year, a group of Japanese scientists found a way to do this in mice and produced “induced pluripotent stem cells” (iPSCs) that were very similar to embryonic stem cells. And just last month, I blogged about two breakthrough papers which showed that human cells could also be reprogrammed into iPSCs.

Now, Jacob Hanna and colleagues from the Whitehead Institute for Biomedical Research, the University of Alabama and MIT, have used these reprogrammed cells to cure a genetic disease – sickle cell anaemia.

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Human skin cells reprogrammed into stem cells

Blogging on Peer-Reviewed ResearchPotential is a sad thing to lose. Have you ever thought that it would be great to return to your childhood, when your options seemed limitless and life hadn’t taken you down increasingly narrow corridors of possibility? Wouldn’t it be great to rewind the clock and have the choice to start over?

Human skin cells are reprogrammed into stem cellsWhile that’s still the stuff of science-fiction, for some cells in your body it may soon be science fact. In one of the most exciting scientific breakthroughs of the year, two groups of scientists have found a way of turning adult human cells back into the stem cells of embryos.

Creating embryonic stem cells

Embryonic stem cells are the embodiment of potential. Armed with a trait called ‘pluripotency‘, they can give rise to every single type of cell and tissue in the body, renewing themselves indefinitely while their daughters take up the mantle of nerves, muscles, blood and more.

For years, stem cells have been touted as the Holy Grail of modern medicine. Within their membranes lies the potential to understand how we develop, test new drugs and most importantly, provide replacement cells to treat Alzheimer’s, Parkinson’s, spinal cord injuries, diabetes, stroke and more.

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Stem cells only grow up properly in the right environment

Stem cells have great potential for treating injury and disease by growing new organs and tissues. Now, a new sutdy shows that stem cells choose which cell type to turn into by measuring how elastic their surroundings are. This discovery may prove the key to getting stem cell transplants to work properly.

 

Children can be fed with good food but they will only become productive members of society if they’re raised in a rich, nurturing environment. Now scientists have shown that the same is true for stem cells.Mouse embryonic stem cells

Our bodies are made up of hundreds of different types of cells, but stem cells can become all of them. For example, one group – the mesenchymal stem cells (MSCs) – can give rise to nerve cells, muscle-building cells, and bone-building cells.

Because of this ability, many scientists have lauded stem cell treatments as the next big thing in medicine. Injuries and diseases could be treated by using a patient’s own stem cells to grow genetically matching tissues and organ.

Some therapies, such as bone marrow transplants for leukaemia patients, are now in limited use and others are at the experimental stage. But overall, progress has been slow and stem cell research has been beset by a range of technical (not to mention moral) difficulties.

The stem cell challenge

One of the main challenges has been finding out how to consistently get stem cells to produce the right type of daughter cell. Stem cells take a wide range of variables into account before they commit to becoming a specific cell type. These include the chemicals and proteins that they are exposed to, how closely packed they are, and even their shape. Adam Engler and colleagues from the University of Pennsylvania can now add another thing to this list – their surroundings.

Like unruly teenagers, stem cells only reach their true potential when they leave home. They only convert into more specific cell types once they’ve dispersed from their place of birth and relocated to new locations around the body. These new environments can be as different as brain, muscle and bone.

Engler and his colleagues have found that the textures of these new homes provide important information to the wandering cells, telling them which cell types to produce. Muscles are 10 times more elastic than bone, and brain tissue is 10 times more elastic still. Engler mimicked these properties by growing MSCs on different consistencies of collagen gels, some more rigid than others.

He found that cells produce nerve cells (neurons) when they grow on soft gels that resemble brain tissue. Others that grow on stiffer muscle-like gels, produce muscle-building cells, or myoblasts. And those grown on rigid gels that mimic bone, produce bone-building cells, or osteoblasts. Even though the cells were exposed to the same chemicals and proteins, they committed to radically different lineages based on how elastic their surroundings are.

Sensing surroundings

A cell's internal skeleton revealedHow do the stem cells measure the stiffness of their environment? Engler thinks that the answer is simple – they pull. Each cell has an internal skeleton of thin fibres that give it support (seen in white in the image on the right). These fibres touch the cell’s outer layer at specific points, and the cell makes contact with its environment at these same points.

By exerting tension along these fibres, the cell can sense how elastic its surroundings are. This information is conveyed through a series of messenger molecules and tells the cell which path to take. It seems that even for stem cells, commitment comes only after a period of tension.

The importance of a stem cell’s environment could have large implications for future research. For example, attempts to treat heart attacks with transplanted stem cells have largely failed. It has proven difficult to convince the transplanted cells to regenerate dead heart muscle, and Engler’s study may tell us why.

Injecting the cells into damaged hearts wouldn’t work because they would be surrounded by scar tissue. To achieve the best results, the stem cells’ new surroundings must be carefully managed to provide the right conditions for their development. The same lesson is relevant to doctors looking to use stem cells to restore wasted muscles or dead nerve tissues. Success may depend on finding out how different stem cells respond to elastic or rigid environments, and how we can imitate these conditions in damaged tissues.

Engler, Sen, Sweeney & Discher. 2006. Cell 677-689