Postmodern Biology: (Adult) (Stem) Cells Are Plastic, Stochastic, Complex, and Uncertain

Complementarity in biological systems: A complexity view

“…Bohr himself pointed out that studying a biological organism, for example, by breaking it up into parts, changes its nature, as compared to a similar organism not being tampered with (i.e., in vitro vs. in vivo). In the case of cell biology, Potten and Loeffler first described “cellular uncertainty” stating: “One of the major difficulties in considering stem cells is that they are defined in terms of their functional capabilities which can be assessed only by testing the abilities of the cells, which itself may alter their characteristics during the assay procedure: a situation similar to the uncertainty principle in physics.” Theise and Krause came to similar conclusions, also through studying adult stem cells, though recognizing that the uncertainty is not limited to stem cells, alone. They stated the principle thus: “any attempt to analyze a cell necessarily alters the nature of the cell at the time of isolation, thereby altering outcomes of subsequent differentiation events.” This uncertainty can be reduced, but not eliminated, in part because of the unavoidability of boundary selection, but also, in part, because of the inherent quenched disorder in all systems.…”

“…What appears to be a unitary (however mobile) entity at one level of scale (a flock of birds, a school of fish, and a green grass prairie) resolves at a lower scale into interacting component organisms; in turn, each animal or plant, when observed at the microscopic scale, dissolves into interacting, self‐organizing cells. Our own bodies are, of course, no different: we are individuals or we are a colony of single cells, some of which contain our own genetic material, but most of which are a very diverse collection of bacteria (Figure ).…”

“…We can go down a further level of scale, to nanometer lengths, and recognize that cells also have no defined, unitary, inherent existence, but—just as flocks resolve into birds, and bodies into cells—cells also dissolve from view, resolving into the interactive, self‐organizing dance of atoms and molecules afloat in aqueous solution . Thus, an alternate, equally verifiable, and potentially powerful model of the body—a classical fluid theory , perhaps—is born . Such a fluid theory may be useful to explain biological phenomena that remain unexplained by cell theory.…”

Stem Cell Fate Analysis Revisited: Interpretation of Individual Clone Dynamics in the Light of a New Paradigm of Stem Cell Organization

“…Although there exist a number of sophisticated purification protocols that are able to select more homogeneous populations of stem cells [16–20], there is always a certain functional overlap of the obtained subpopulations. Furthermore, there is accumulating evidence that the phenotypic properties of HSC are reversibly changing ( phenotypic reversibility ) [21–28] and that tissue stem cells specified for one type of tissue can be manipulated such that they can act as stem cells of another tissue ( stem cell plasticity ) [29–32]. Even though there are most likely a number of constraints in the developmental options, these observations point to the fact that the functional potential of a stem cell cannot be uniquely determined by its actual phenotypic appearance.…”

The stem cell niche and tissue biology

“…Finally, the original niche concepts for the function of specific adult stem cell populations in adult organs establish a much broader paradigm for biological research (5,6). The concept can be extended to stem cells in earlier stages of development, including the embryonic stem cells, but also to other cell types (see Lensch et al and Badillo and Flake, this issue).…”