explains Dr. Paola Romagnani,
a Professor of Nephrology at the University Meyer Children's Hospital of
"Up until recently, it was believed that
function recovery after the injury
was a consequence of regeneration involving all specialized cells simply
ignoring that such cell divisions would imply a further potentially
life-threatening decline of residual organ function,"
How do the Cells Help Restore Function of
Failing Organ ?
Since it has
been known that regeneration of all specialized cells is not responsible for the recovery
of function in the organs, it has also been understood that there are two types
of cells that react to organ failure.
"The majority of cells in an organ are highly
specialized cells that have lost the ability for cell division but that can
enhance their working capacity. In contrast, a minority of cells is
un-programmed, like a stem
cell, and able to divide
says Dr. Romagnani. "Armed
with this knowledge, we wanted to understand how the two processes worked
together to help an organ recover from failure,"
she added. Only the stem-like cells have the ability to
divide quickly and replace the damaged cells, whereas, the cells in specialized
organs like kidneys, liver and heart have only specific tasks to perform. "Skin, for example, performs the same function
wherever it is, which makes rapid cell division an effective way to repair skin
damage. Indiscriminate replication of specialized organ tissue, however, would
reduce an organ's health more than it would help,"
On how the
specialized cells react, she said, "This is why the cooperation between the two
cell types is so important. The specialized cell will replicate its
DNA, but not divide, which is a process known as endoreplication. By doing
that, the cell is still able to function and the amount of work it can do greatly
increases--it's making up the work of cells that have died. Simultaneously, or
shortly after cells have endoreplicated, you have the stem-like cells rapidly
dividing to replenish lost tissue."
Organ Regeneration - Is One Technique Better
than the Other?Certain organs seem to be highly relevant on one
technique than others, Dr. Romagnani and her team found while studying the
interaction between the two cell types.
The following example
illustrates this point - "The heart tends
to have smaller densities of stem-like cells than the liver, for example, which
means the heart responds to organ failure largely with endoreplication of
specialized cells and to a lesser degree with cell regeneration."
other hand, "In the liver, cell
regeneration will occur more readily; but regardless of the more dominant
reaction, both responses play critical roles in both organs."
pros and cons attached to both the recovery responses, which may have
implications for developing medication which in turn may encourage one of the
two responses over the other.
"Endoreplication is a way to quickly increase
cell size and function undergoing hypertrophy, which is great in the short term
because it can save a life, but in the long run, having a high proportion of
cells in this state can result in chronic organ dysfunction due to the
breaking-down of tissues,"
Dr. Romagnani elaborated on the point.
case of cell division in stem-like cells, while in the long run, the
tissue strength is better, there are also chances of cancer developing in the
affected organ. "When you have a high
number of cells that are efficient at dividing, you have a higher risk of
cancer. These significant tradeoffs are likely why both methods exist and why
it's so important for them to be balanced,"
says Dr. Romagnani.
The Way Forward for Reversing Organ failure
and her team are now looking forward to making use of this finding in
developing treatments for acute organ failure. "Understanding the role of
endoreplication in coordination with cell replication in each organ is really
important. Researchers need to know that there are two mechanisms going on and
that we need to target them separately. Currently, we don't have specific drugs
for acute organ failure because up until now, trying to find a solution was
utterly impossible. Now, we can take the next step,"
- Surviving Acute Organ Failure: Cell Polyploidization and Progenitor Proliferation - (https://doi.org/10.1016/j.molmed.2019.02.006)