Regeneration of chronic liver patient may be possible, say Harvard researchers -
The Harvard researchers find switch that causes mature liver cells to revert to stem state the cell as
researchers, led by Fernando Camargo, PhD, happened upon this discovery while investigating whether a biochemical cascade called Hippo, which controls the size of the liver develops, also affects cell fate. The unexpected response, published in the cell log , is that cleavage of the Hippo-signaling pathway in mature liver cells generates very high levels of dedifferentiation. This means that cells turn back the clock to become stem cells as new, enabling them to give birth to functional progenitor cells that can regenerate a diseased liver.
The liver is a regenerative model for decades, and it is well known that mature liver cells can reproduce in response to injury. Although three quarters of the liver is surgically removed, the only duplication could return the body to its mass of normal operation. This new research indicates a second mode of regeneration that repairs can be less radical, but more constant damage liver, and chip away at a long-standing theory that there is a pool of stem cells in the liver waiting to be activated.
"I think this study highlights the tremendous plasticity of mature liver cells," said Camargo, who is an associate professor in the Department of the Harvard Stem Cell and Regenerative Biology, and on the basis of stem cell program at children's Hospital Boston. "It is not that you have a very small population of cells that can be hired for an injury ;. Nearly 80 percent of hepatocytes [liver cells] can undergo this change cell fate "
Much biology dissection of the work of these changes and establish the dedifferentated cells are functional progenitors was performed by the first co-authors of cell paper Yimlamai Dean, MD, PhD, and Constantina Christodoulou, PhD, children's Hospital Boston.
the next step, Camargo said, would be to understand how the activity of Hippo changes in cells affected by chronic liver injury or diseases such as hepatitis. in the long term, this work could lead to drugs that manipulate the Hippo activity of mature liver cells inside patients to stimulate dedifferentiation and speed healing.
It might also be possible to control Hippo signaling to grow countless progenitor liver cells in a laboratory dish for transplantation, which Camargo team continued in cell using mice born with a genetic liver disease. They grew healthy liver stem cells and transplanted into the diseased mice. Over a period of three or four months, the cells of the transplanted liver grafted and animals have seen improvements in their condition.
"People have tried to use grafts of liver cells for metabolic diseases since the early 0s, but because of the source of cells discarded livers they have failed," said Camargo. "with this unlimited source of cells from a patient, we think that maybe it's time to think again to hepatocytes or progenitor cell transplantation in the context of genetic disorders of the liver."
the observation that mature liver cells dedifferentiate comes after a number of related studies published in the last year Harvard researchers showing that the mature cells in several different internal organs, including the kidneys, adrenal glands and lungs, are more plastic than we once assumed.
"I think maybe there is something that people have neglected because the field was so the cells centered rod" said Camargo, also a senior faculty member of Harvard stem cell Institute. "But I think the bottom line is that the cells we have in our bodies are plastic, and the understanding of the pathways underlying this plasticity may be another way of potentially manipulating regeneration or expansion of a kind of cell type for regenerative medicine. "
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