Despite the fact organ failure can take your life, organs like kidney, heart, and liver are always prepared for such a catastrophe. Developing research underpins the finding of the two cell types that quickly work and respond together in order to achieve the proper functioning of the organ.
To start with, the surviving cells go into overdrive, making an attempt to keep the organ working while stem-like cells start restoring the damaged tissue. The research got published in the journal Trends in Molecular Medicine on 29 March which explains how this dual-response action can save lives.
“When tissue is injured, cells divide to replace it, but the process of cell division in specialized cells would prevent the cell from performing its normal duties. In situations where an organ is failing, which means the organ already isn’t functioning properly, your body can’t afford to have many cells stop working,” says Paola Romagnani, a lecturer of nephrology at the University Meyer Children’s Hospital of Florence.
“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.”
That changed when it was understood that there are in reality two kinds of cells that respond 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 efficiently,” says Romagnani.
“Armed with this knowledge, we wanted to understand how the two processes worked together to help an organ recover from failure.”
Since cells in particular organs, for example, the heart, kidneys, or liver are modified to perform specific functions, it is only the stem-like cells which can quickly carry out the division and restoring process of damaged tissues.
“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,” says Romagnani.
“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,” Romagnani says.
“Simultaneously, or shortly after cells have endoreplicated, you have the stem-like cells rapidly dividing to replenish lost tissue.” During the research, Romagnani found out that there are some organs which depends more on this technique than the other organs.
“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,” she says.
“In the liver, cell regeneration will occur more readily; but regardless of the more dominant reaction, both responses play critical roles in both organs.”
“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,” Romagnani says. “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.”
On account of cell division in stem-like cells, tissue strength is a better long haul, yet so are the chances for developing cancer in the influenced organ. “When you have a high number of cells that are efficient at dividing, you have a higher risk of cancer,” she says. “These significant tradeoffs are likely why both methods exist and why it’s so important for them to be balanced.”
Pushing ahead, Romagnani and her partners are keen on applying this data to develop medications for serious cases.
“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,” she says.
“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.”