In fact, there have been many recent examples of stem cells
that have been induced to initiate morphogenesis in a laboratory setting (in
vitro). These studies have been outlined
in a review article by Drs. Toshiro Sato and Hans Clevers from the Department
of Gastroenterology at the Keio University School of Medicine in Tokyo, Japan
that appeared in the journal Science,
Vol. 340. June, 2013. The example the
reviewers cite came directly from their own efforts. In their studies, they have successfully initiated
morphogenesis in the laboratory in three-dimensional human cell cultures that
resulted in the elaboration of what they refer to as, “Mini-Guts.”
One of the reasons they chose the small intestine as their
in vitro model is because this organ has a higher self-renewal rate than any
other mammalian tissue. In fact, all the
cells within the small intestine are renewed within five days. The reason for this remarkable rate is due to
the activity of a particular stem cell. This
stem cell type possesses a unique protein receptor on its surface, Lgr5, that
binds preferentially with R-spondins a type of protein essential to the process
of morphogenesis. These Lgr5+ cells
differentiate into a host of cell types that constitute a healthy and
functional small intestine. In addition,
these Lgr5+ cells persist throughout the entire life of the organism.
To accomplish the successful in vitro production of
mini-guts- epithelial organoids - that retain the identity and properties of
the original tissue, the investigators used Matrigel that is, in fact, a laminin and
collagen-rich matrix that simulates the structural components of the basal
lamina of the small intestine. Additional
factors and components that represent the minimal requirements for stem cell
growth were also added to this matrix.
This impressive accomplishment has profound implications for
the study of disease processes. For
example, it is now feasible to use this same methodology to produce mini-guts
from cells derived from patients with adenomas and colorectal cancers. These organoids could then be studied alongside
of organoids derived from normal tissue. Such studies could prove invaluable in
understanding and delineating the etiology of these illnesses.
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