Prospects for Regeneration of Organs Without Stem Cells

Biology is enormously complex, and it should never really be a surprise to find that different parts of the body have evolved different methodologies for achieving the same goal - such as tissue maintenance, to pick one example. So while it seems to be the case that small populations of stem cells support most or all of our tissues, offering the opportunity for researchers to build therapies based on enhancing the activities or increasing the numbers of these stem cells, there may be some exceptions to this rule. There may also be separate and distinct methods of tissue maintenance that operate in parallel to one another, and until they have been discovered and cataloged who can say whether one might be easier to manipulate than the others? At this point all could be candidates for regenerative therapies.

In this context, here is an interesting report on recent research into kidney regeneration, which strongly suggests that stem cells are not the agent at work here:

A new model for organ repair

Harvard Stem Cell Institute (HSCI) researchers have a new model for how the kidney repairs itself, a model that adds to a growing body of evidence that mature cells are far more plastic than had previously been imagined. After injury, mature kidney cells dedifferentiate into more primordial versions of themselves, and then differentiate into the cell types needing replacement in the damaged tissue. This finding conflicts with a previously held theory that the kidney has scattered stem cell populations that respond to injury.

Benjamin Humphreys [was] suspicious of the kidney stem cell repair model because his previous work suggested that all kidney cells have the capacity to divide after injury. He and his colleagues decided to test conventional wisdom by genetically tagging mature kidney cells in mice that do not express stem cell markers; the hypothesis being that the mature cells should do nothing or die after injury. The results showed that not only do these fully differentiated cells multiply, but they can multiply several times as they help to repair the kidney. This new interpretation of kidney repair suggests a model by which cells reprogram themselves; similar to the way mature cells can be chemically manipulated to revert to an induced pluripotent state.

"One has to remember that not every organ necessarily is endowed with clear and well-defined stem cell populations, like the intestines or the skin. I'm not saying that kidney stem cells don't exist, but in tissues where cell division is very slow during homeostasis, there may not have been an evolutionary pressure for stem cell mechanisms of repair." He plans to apply his kidney repair discovery to define new therapeutic targets in acute kidney injury. The goal would be to find drugs that accelerate the process of dedifferentiation and proliferation of mature kidney cells in response to injury, as well as slow down pathways that impair healing or lead to scar tissue formation.

Below is a link to the paper, which is unfortunately not open access:

Differentiated kidney epithelial cells repair injured proximal tubule

When epithelial cells in the proximal portion of the nephron are damaged they rapidly proliferate to repair the damage to the kidney. Whether a stem cell is responsible for this proliferative response or not is controversial. Although a scattered population of cells can be found in the human proximal tubule that seem to have stem-cell characteristics, they could also represent isolated damaged cells that have dedifferentiated and lost their epithelial characteristics. We resolve these conflicting models using genetic lineage analysis to demonstrate that fully differentiated proximal tubule cells not only proliferate after injury, but they also upregulate apparent stem-cell markers. This study shows that epithelial dedifferentiation is responsible for repair of mouse proximal tubule, rather than an adult stem-cell population.
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