June 01, 2004
Duke Researchers Turn Fat Tissue Cells Into Nerve Cells

Duke University researchers have demonstrated the ability to extract stromal cells from mouse fat tissue and convert it into nerve cells.

DURHAM, N.C. -- Two years after transforming human fat cells into what appeared to be nerve cells, a group led by Duke University Medical Center researchers has gone one step further by demonstrating that these new cells also appear to act like nerve cells.

The team said that the results of its latest experiments provide the most compelling scientific evidence to date that researchers will in the future be able to take cells from a practically limitless source -- fat -- and retrain them to differentiate along new developmental paths. These cells, they said, could then be used to possibly treat a number of human ailments of the central and peripheral nervous systems.

The results of the team's latest experiments were published June 1, 2004, in the journal Experimental Neurology.

Using a cocktail of growth factors and induction agents, the researchers transformed cells isolated from mouse fat, also known as adipose tissue, into two important nerve cell types: neurons and glial cells. Neurons carry electrical signals from cell to cell, while glial cells surround neurons like a sheath.

"We have demonstrated that within fat tissue there is a population of stromal cells that can differentiate into different types of cells with many of the characteristics of neuronal and glial cells," said Duke's Kristine Safford, first author of the paper. "These findings support more research into developing adipose tissue as a viable source for cellular-based therapies."

Over the past several years, Duke scientists have demonstrated the ability to reprogram these adipose-derived adult stromal cells into fat, cartilage and bone cells. All of these cells arise from mesenchymal, or connective tissue, parentage. However, the latest experiments have demonstrated that researchers can transform these cells from fat into a totally different lineage.

Earlier this year, Duke researchers demonstrated that these adipose-derived cells are truly adult stem cells. As a source of cells for treatment, adipose tissue is not only limitless, it does not carry the potentially charged ethical or political concerns as other stem cell sources, the researchers said.

"This is a big step to take undifferentiated cells that haven't committed to a particular future and redirect them to develop down a different path," said Duke surgeon Henry Rice, M.D., senior member of the research team. "Results such as these challenge the traditional dogma that once cells become a certain type of tissue they are locked into that destiny. While it appears that we have awakened a new pathway of development, the exact trigger for this change is still not known."

For their latest experiments, the researchers demonstrated that the newly transformed adipose cells expressed many similar cellular proteins as normal nerve and glial cells. Furthermore, they showed that the function of these cells is similar to nerves.

The problem of how to change differentiated cells (cells specialized to perform particular functions) into less differentiated cells is obviously very solvable. Differentiation of cells into specialized types is not a one way street. This should not be too surprising. Cells are made up of matter and matter is malleable. The arrangement of the cellular matter that determines cellular type (known as epigenetic information) is becoming steadily more malleable with each discovery of how to manipulate cells. Recently Scripps researchers found a compound they labelled reversine that converts differentiated cells into stem cells. They had to search through only 50,000 compounds to find one that would do that. Surely there are huge numbers of other compound waiting to be discovered that will dedifferentiate (i.e. despecialize) cells to turn them back into stem cells and even turn them all the way back into the equivalent of embryonic stem cells.

Embryonic stem cells may turn out to provide a starting point for therapy development that allows the more rapid development of some types cell therapies. But there is no treatment that can be developed from embryonic stem cells that won't also eventually be solvable using adult stem cells or fully adult differentiated cells as starting points. Of course, in the short term one can understand why those who have no moral qualms about using embryonic stem cells want to see them used to develop therapies. Embryonic stem cells may save some lives. But for those who will need cell therapy-based treatments in the medium to long term the debate about embryonic stem cell therapy will probably have no impact on the availability of treatments.

Share |      Randall Parker, 2004 June 01 02:31 PM  Biotech Organ Replacement

Fly said at June 1, 2004 4:17 PM:

ďDifferentiation of cells into specialized types is not a one way street.Ē

Some changes are one-way. Some immune cells make specialized antibodies by excising all but one combination of precursor antibody DNA. Once this occurs they canít produce any other antibody. As another extreme example, red blood cells, having no nucleus, cannot be de-differentiated.

Those cells that can be de-differentiated are very exciting. What sets such a cellís state? (Iím viewing such cells as chaotic non-linear dynamic systems with attractors representing cell types. What factors push the cell from one attractor to another?)

Genes turned off by methylation or phenylation or unknown process.
Genes turned on by promoters or off by inhibitors. (Concentration dependent.)
RNAi stopping protein synthesis. (Maybe proteins that inhibit protein formation or folding will also be found.)
Chromosome structure, e.g., telomers.
Surrounding physical environment. Contact with neighbors or stretching or squeezing triggers cell changes. Even temperature can change a cellís type.
Chemical environment. Signaling hormones, growth factors.
Growth environment. Nutrient supply.
Cellular aging such as gene damage, protein damage, accumulated garbage.

It is interesting that replacing an egg cellís nucleus with a mature, differentiated nucleus can result in a clone. For what somatic cells does this work? If some cell types never work then why not?

When biologists know how this stuff works, I believe we will be able to regenerate our bodies. Faster please.

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