April 12, 2009
Safer Way To Convert Adult Cells To Pluripotent Stem Cells

The ability to convert adult cells from our own bodies into pluripotent (capable of becoming all cell types) cells that resemble embryonic stem cells would allow the development of cell therapies that are immunologically compatible with each person's immune system. Efforts to make cell type conversion safer keep getting better and better. The problem is how to convert the cells without DNA damage that can lead to cancer. Some UCSF researchers just took another step in this direction by reducing the number of genes that need to be inserted into adult cells to convert them into pluripotent stem cells.

A team of UCSF researchers has for the first time used tiny molecules called microRNAs to help turn adult mouse cells back to their embryonic state. These reprogrammed cells are pluripotent, meaning that, like embryonic stem cells, they have the capacity to become any cell type in the body.

The findings suggest that scientists will soon be able to replace retroviruses and even genes currently used in laboratory experiments to induce pluripotency in adult cells. This would make potential stem cell-based therapies safer by eliminating the risks posed to humans by these DNA-based methods, including alteration of the genome and risk of cancer.

"Using small molecules such as microRNAs to manipulate cells will play a major role in the future of stem cell biology," says senior author Robert Blelloch, MD, PhD, of the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research at UCSF.

It says something (not good) about the state of gene therapy that scientists find it necessary to develop techniques that avoid the need to put genes into cells in order to achieve therapeutic results.

These scientists still need to rely on genes introduced using viruses. But they were able to reduce the number of genes from 4 to 3. They intend to do more work to develop more microRNA molecules that will substitute for the remaining 3 genes.

Previous methods for creating embryonic stem cell-like cells have relied on the introduction of DNA that encodes four transcription factors, proteins that play a role in the production of genes. The limitation of this method is that three of the four genes that code for these transcription factors -- oct4, klf4 and c-myc are oncogenes, meaning they promote the uncontrolled cell growth characteristic of cancer.

In the current study, led by Robert Judson, a graduate student in the Blelloch lab, the scientists induced pluripotency using a combination of infection and transfection. The infection involved introducing three viruses, each containing a transcription factor known to induce pluripotency. The transcription factor for c-myc was not included. The transfection involved a simple process in which the tiny microRNA molecules were mixed with a lipid, allowing them to pass through the cell membrane. By labeling the fibroblast cells, they showed that the treated cells could be incorporated into a mouse embryo and become every cell type in the adult animal -- including germline cells that would produce the next generation of mice.

Once they've eliminated the need for genes carried by viruses These scientists also want to go even farther and use microRNAs to turn cells into whatever cell types are needed in therapy.

Currently, Blelloch and his colleagues are working to replace all four transcription factors with microRNAs and conducting experiments that will reveal the mechanism by which these small molecules are able to induce pluripotency. The team will also be looking to determine which microRNAs might be able to turn adult cells directly into particular adult cell types, by-passing the embryonic stem cell-like stage altogether.

These folks and researchers in other labs will surely succeed in finding ways to convert cells into large numbers of different cell types. Just being able to create certain desired cell types and inject them into some locations in the body will be enough to treat some problems. But other problems will require additional tissue engineering technology in order to create complex 3 dimensional structures. For example, the ability to create a nerve cell isn't enough to bridge across a severed spinal cord. The axons and dendrites of the nerves and supporting cells must form complex relationships in order to carry signals up and down the spinal cord.

Lots of organs are made up of multiple types of cells arranged to work together to perform organ functions. To grow individual organs requires the creation of 3 dimensional biochemical and physical micro-environments which growing organs encounter during embryonic development. Tissue engineering for organ growth requires not just the ability to convert cells into different cell types but also to orchestrate the arrangement of cells of multiple types. When this becomes a solvable problem human bodies will become as fixable as cars with one exception - the brain. The brain is the long pole in the tent for full body rejuvenation. To rejuvenate the brain will require solving an even larger and harder set of problems.

Share |      Randall Parker, 2009 April 12 11:21 PM  Biotech Stem Cells

Anonymous said at April 13, 2009 1:03 AM:

GM FOODS IS PEOPLE! Won't somebody think of the cannibals?

Seriously, the fact that they're fiddling with genes and "don't cause cancer" is a practical constraint makes me feel like I'm living in the future (in the good way).

David Govett said at April 13, 2009 12:54 PM:

As for saving the brain. We'll do what operating systems do: Store the contents at, say, weekly checkpoints. Then, when necessary, we'll use nanobots to construct a new brain, and we'll structure it according to the information saved at a desired previously saved date and swap it in. Voila!

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