Tissues may use diverse mechanisms to replace lost cells

December 11, 2015
In an article published in Science this week, Prof. Hans Clevers discusses the role of stem cells in tissue renewal. Clevers, group leader at the Hubrecht Institute and Professor of Molecular Genetics at University Medical Center Utrecht and Utrecht University, states that there may not be general rules as to how tissues are renewed. Instead of stem cells, tissues might allow differentiated cells to proliferate directly and replace lost tissue.

“In the end, there may be no general rules as to how tissues are renewed, as there is no end to the inventive power of evolution”

The paradigm of hematopoietic stem cells, able of self-renewal and differentiation, serves as a template to interpret experimental observations on other mammalian tissue. However, fitting observations on solid tissues into this paradigm has led to more questions than answers. Organs are different in function, design and size and subject to different biological and physical challenges. This makes it plausible to assume that tissues have evolved different ways of restoring the number of cells.

In the article, prof. Clevers describes the development of cell culture technologies in the 1970s. These allow extensive expansion of proliferate epidermal cells to save for example burn patients. However, the identity of the epidermal stem cell has remained controversial ever since. No stem cell has been found to serve as the epidermal stratum basale. Similar situations occur in the esophagus, intestinal crypts, stomach glands and the testis. The tissues harbor an explicit tissue renewal function but it is distributed over a large cell population.

Prof. Clevers states that the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost tissue.

“ Stem cell function may indeed be embodied in hard-wired professional stem cells in some tissues. But stem cell function may also diffusely be contained within much larger populations of neutrally competing, undifferentiated cells. It may be executed by facultative stem cells, opportunistically recruited from committed or even from fully differentiated cell populations. Tissues might avoid the use of undifferentiated stem cells altogether, by allowing differentiated cells to proliferate directly and thus to replace lost tissue. In the end, there may be no general rules as to how tissues are renewed, as there is no end to the inventive power of evolution.”