Featured Achievement

A Breakthrough in Adult Stem Cell Propagation

Progress toward biomedical advances based on adult stem cell bioengineering has been at an impasse because of one universal property of adult stem cells: They are nearly impossible to expand and propagate in culture. A researcher at MIT's Biotechnology Process Engineering Center (BPEC) has published a report that outlines a new concept for adult stem cell expansion research. This report may revolutionize thinking about this challenging problem in cell biological engineering and accelerate progress toward realization of the biotechnological promise of adult stem cell research (Sherley, 2002, Stem Cells 20, 561-572).

Stem cells are rare precursor cells in adult tissues that divide to produce progeny cells that mature into functional tissue cells. In this way, adult stem cells function to replenish mature tissue cells that have expired or to repair tissues and organs that are diseased or damaged. These natural restorative properties make adult stem cells attractive for development for use in gene therapy and cell replacement therapies, respectively.

To perform their tissue renewal functions, stem cells must produce differentiating cells while simultaneously maintaining their own undifferentiated, proliferative state. Sherley recognized that this essential adult stem cell property, called asymmetric cell kinetics, is also a major barrier to expansion in culture. The reason for the difficulty in propagating adult stem cells is that in culture they are lost in the sea of differentiating cells that they produce. Unlike adult stem cells that have life-long division capability, differentiating progeny cells mature, arrest, and die. Thus, progeny cells are inadequate for gene and cell therapies that require long-term tissue reconstitution.

Sherley describes the concept of suppressing the asymmetric cell kinetics (SACK) of adult stem cells by manipulating cellular pathways that control their cell kinetics. Conversion of adult stem cells to symmetric cell kinetics promotes their own expansion. Because asymmetric cell kinetics is a universal property of adult tissue stem cells, the SACK concept should have broad application to adult stem cells from diverse mammalian species and tissues.
© AlphaMedPress 1066-5099/2002

To learn more about this topic:
Contact MIT's Biotechnology Process Engineering Center (BPEC), http://web.mit.edu/bpec/research/StemcellVehicleSubthrusta2c.html

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© AlphaMedPress 1066-5099/2002

The asymmetric cell kinetics barrier to expansion
of adult stem cells in culture. When tissue cells are
explanted to culture, a large number (N) of adult stem
cell-based tissue turnover units is obtained. Green
circles represent adult stem cells, blue and yellow circles indicate differentiating transit cells, and circles
depict mature terminally arrested cells that together
comprise the basic turnover unit. It is postulated that,
in culture, these tissue units regain their basic
asymmetric cell kinetics even though phenotypic
differentiation of progeny cells is not restored. Because
adult stem cell number does not increase during
asymmetric cell kinetics, the stem cell function
decreases with time as transit cells accumulate and
fill up culture vessels. After the initial transfer of cells
to culture (Po), successive dilutions of replete cultures
(Pn-i) eventually yield a culture dilution in which no
stem cells are transferred (Pn). This event is soon
followed by a complete replicative arrest of the culture
when all transit cells complete terminal maturation and
division arrest [25]. Schematic graphs (cell number,
CN, versus time, t) deplete changes in growth rate
with successive passages in culture.

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Last modified: October 16, 2003