Monday, April 28, 2008

Regenerative medicine inspired by a Newt

Student post submitted by Sheena Edmonds


ResearchBlogging.orgResearchers in the field of regenerative medicine are turning their attention to a potentially new source of stem cells. This new source is generated directly from ones own cells that were previously thought to be terminally differentiated. If scientists are correct they will be able to take any cell in the body and dedifferentiate it so that it goes from a more differentiated state to a less differentiated state. This phenomenon is most frequently seen in invertebrates like earthworms and amphibians. When an earthworm is cut in two it has the ability to regenerate into two identical worms. Newts have been reported to have the ability to regenerate entire limbs, tail and even their spinal cord. Unfortunately, mammals are a little more restricted in their ability to regenerate parts of their body due to irreversible differentiation in certain tissues. Aside from this, researchers believe that by studying the mechanism by which newts restore their tissues by dedifferentiation they might discover a molecular signal that can be incorporated into humans that would allow them to rejuvenate damaged tissue through dedifferentiation. This is thought to be more beneficial than organ transplants, tissue engineering, and even stem cell therapy because the cells involved in dedifferentiation come from the patient going through treatment. By using ones own cells there is no risk of initiating an immune response and no chance of rejection. In addition, ethicists might be more favorable to this type of regenerative medicine as opposed to embryonic stem cells. (continues below...)


fig13_12.jpgMore studies are being done to determine how exactly this process works. At the genetic level the cells gene activation is repressed and genes that keep the cell in an undifferentiated state are turned on. Once these genes are turned on the cell can reenter the cell cycle (Cai, 2007). The most familiar example of this process is the ability of a newt to grow back its tail after having it amputated. By studying the unique behavior of newts and examining this adaptation they have, researchers believe they can uncover the exact signaling that initiates a phenotypic reversion of fully differentiated cells. Studies indicated that once the tail is amputated the epithelial cells migrate and form a mature epithelium cap at the end of the wound. The internal cells underlying the cap lose their tissue characteristics and dedifferentiate in response to an unknown signal. The dedifferentiated cells proliferate and form a mass of pluripotent cells that are capable of redifferentiating. These pluripotent cells then build a replica of the missing tail (Cai, 2007). It is clear that this event does happen, however, the goal is to discover what molecular signals make it occur.


An experiment was done that utilized immature muscle cells of newts and mice. The two types of myoblasts were grown together and induced to differentiate into skeletal muscle fibers. Some of the newt myoblasts fused with the mouse myoblasts and created a hybrid. The hybrid cells were isolated and stimulated with serum (Cai, 2007). The serum was expected to cause the newt myotube to synthesize DNA but they did not expect the mouse myotube to do the same. Shockingly, the mouse myotube also began to synthesize DNA which indicated that there was something in the newt myotube nuclei that made the mouse myotube nuclei able to respond to the serum (Cai, 2007). In yet another experiment, the mouse myotube dedifferentiated when it was treated with extract derived form the regenerating limb of the newt implying the signal that initiates dedifferentiation was in the extract. Researchers subjected the extract to chemical and physical treatment including lipid removal, boiling, and trypsin digestion. The results proved the signal within the extract was a protein (Cai, 2007). Moreover, these two experiments confirm that mammalian cells can dedifferentiate when stimulated with the right factors. Identification of the exact molecules would aid in studying the mechanism for dedifferentiation which could eventually be used to regenerate tissue in vivo.


Researchers have now directed their attention to studying the dedifferentiation process that occurs in human myoblasts. They found that ciliary neurotrophic factor (CNTF) plays an important role in regulating many processes with in the nervous system. They also found that there are an abundance of CNTF receptors in human skeletal muscles (Cai, 2007). More excitingly they tested the affects of CNTF and found that it induced committed myoblasts to dedifferentiate into mulitpotent cells. Not only could these cells restore skeletal muscles, they also have the ability to differentiate into new tissues such as neurons, glial cells, and smooth muscle cells (Cai, 2007).


By investigating the way invertebrates adapt to the stresses and strains of their environment researchers have come closer to discovering the mechanism by which cells that were previously thought to be permanently differentiated can work backwards to their original pluripotent cells. This new method for regenerative medicine is one of the many breakthroughs in modern science. Dedifferentiation of one’s own cells offers many advantages over other researched treatments. It poses little threat of initiating an immune response and it is morally more correct then utilizing human embryonic stem cells.


Reference:



CAI, S., FU, X., SHENG, Z. (2007). Dedifferentiation: A New Approach in Stem Cell Research. BioScience, 57(8), 655. DOI: 10.1641/B570805

Additional related articles:



Cells That Go Back In Time


Mammalian myotube dedifferentiation induced by newt regeneration extract




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