delanceyplace.com 3/19/10 - hope and the p21 gene
In today's excerpt - new hope for the regeneration of tissue in humans based on experiments with mice and similar in type to the regeneration of tissue and limbs in creatures like newts flatworms and sponges:
"A quest that began over a decade ago with a chance observation has reached a milestone: the identification of a gene that may regulate regeneration in mammals. The absence of this single gene called p21 confers a healing potential in mice long thought to have been lost through evolution and reserved for creatures like flatworms, sponges, and some species of salamander.
"In a report published in the Proceedings of the National Academy of Sciences, researchers from The Wistar Institute demonstrate that mice that lack the p21 gene gain the ability to regenerate lost or damaged tissue.
"Unlike typical mammals, which heal wounds by forming a scar, these mice begin by forming a blastema, a structure associated with rapid cell growth and de-differentiation as seen in amphibians. According to the Wistar researchers the loss of p21 causes the cells of these mice to behave more like embryonic stem cells than adult mammalian cells and their findings provide solid evidence to link tissue regeneration to the control of cell division.
" 'Much like a newt that has lost a limb, these mice will replace missing or damaged tissue with healthy tissue that lacks any sign of scarring' said the project's lead scientist Ellen Heber-Katz Ph.D. a professor in Wistar's Molecular and Cellular Oncogenesis program. 'While we are just beginning to understand the repercussions of these findings perhaps one day we'll be able to accelerate healing in humans by temporarily inactivating the p21 gene.'
"Heber-Katz and her colleagues used a p21 knockout mouse to help solve a mystery first encountered in 1996 regarding another mouse strain in her laboratory. MRL mice [a strain of mouse that exhibits remarkable regenerative abilities for a mammal], which were being tested in an autoimmunity experiment had holes pierced in their ears to create a commonly used life-long identification marker. A few weeks later investigators discovered that the earholes had closed without a trace. While the experiment was ruined it left the researchers with a new question: Was the MRL mouse a window into mammalian regeneration? ...
"[Researchers] found that p21 a cell cycle regulator was consistently inactive in cells from the MRL mouse ear. P21 expression is tightly controlled by the tumor suppressor p53, another regulator of cell division and a known factor in many forms of cancer. The ultimate experiment was to show that a mouse lacking p21 would demonstrate a regenerative response similar to that seen in the MRL mouse. And this indeed was the case. As it turned out p21 knockout mice had already been created, were readily available, and were widely used in many studies. What had not been noted was that these mice could heal their ears.
" 'In normal cells p21 acts like a brake to block cell cycle progression in the event of DNA damage preventing the cells from dividing and potentially becoming cancerous' Heber-Katz said. 'In these mice without p21 we do see the expected increase in DNA damage but surprisingly no increase in cancer has been reported.' "
|Bedel-Baeva, Snyder, Gourevitch, Clark, Zhang, Leferovich, Cheverud, Lieberman, and Heber-Katz|
|Lack of p21 expression links cell cycle control and appendage regeneration in mice|
|Proceedings of the National Academy of Sciences of the United States of America|