September 24, 2022

Assumptions of stem cell biology questioned

Is “stemness” like phlogiston?
Simple-minded
laymen may believe that scientists are on the verge of being able to
manipulate stem cells. But some thoughtful biologists are questioning
the very notion of what a stem cell is.

An opinion
piece by Arthur Lander in the open-access Journal
of Biology
, argues
that the idea of stem cells could be a dead end, much like the
mysterious substance “phlogiston” which was sought by chemists in
the 18th century. Before it was learned that matter burns by taking
up oxygen, chemists explained combustion as the release of
phlogiston. Only when it came to pinning down its distinctive
physical properties did it become clear that phlogiston did not
exist.

Professor
Lander, Director of the Center for Complex Biological Systems at the
University of California, Irvine, argues that neither of the two
properties that define “stem cells” as they are popularly
discussed, potency and self-renewal, can be ascribed an exclusive
molecular basis, and that both are seen in cell types not usually
described as stem cells.

He said, "It
is curious that, after 45 years, we are unable to place the notion of
‘stemness’ on a purely molecular footing. Of course, the fact that a
goal has not been achieved after a long time does not mean that the
answer is not around the corner. But it does give one cause to wonder
whether something we are doing needs to change, either in the
question we are asking or the way we are approaching it".

Lander feels
that “stemness” should be considered a property of systems,
rather than individual cells. A system with stemness is one that can
achieve a controlled size, maintain itself homeostatically, and
regenerate when necessary. He argues that such behaviors naturally
emerge as a consequence of basic engineering principles of feedback
control.

One practical
consequence of an inaccurate understanding of the precise nature of
stem cells may be the assumption that targeting of “cancer stem
cells” with chemotherapy will stop tumors.

In an
interview in The Scientist
,
Professor Lander explained that like phologiston, “the concept [of
stem cells] can have a perfectly good operational definition and
still refer to nothing that actually exists”. It could be that if
stem cells are taken out of their context, or “niche”, they may
not behave the way that they do in a living organism.

What about the
latest development, pluripotent stem cells created from skin cells by
reprogramming 3 or 4 genes? Lander says that this could be a red
herring. The unipotent skin cell certainly becomes pluripotent, but
it may not be a genuine stem cell.

Lander is not
arguing that work with stem cells is a waste of time. The notion of
phlogiston was a conceptual breakthrough that helped chemists conduct
experiments and share ideas and eventually led to the correct
explanation. But his unconventional theory does suggest that
regenerative medicine may still have a long way to go. ~ Journal
of Biology, Sept 21
;
The
Scientist, Sept 29