Tokyo University. Japan: Cultured small intestinal stem cells were successfully transplanted onto injured colons of recipient mice. Grafted small intestinal stem cells were able to reconstitute self-renewing epithelia. Transplanted stem cells gave rise to tissues retaining phenotype and morphology of the small intestine without changing their fate into colonic phenotype. This study provides proof of principle for the stem cell therapy for small intestinal diseases.
Despite having some common features, epithelia of the small intestine
(SI) and colon show many differences. They differ in their structures as
well as their cellular components, as exemplified by Paneth cells that
reside only in the SI. For future advancement of stem cell
therapy for SI diseases, it is essential to investigate whether SI
epithelial stem cells, that are taken from the body and grown in the
laboratory, are able to reconstitute the normal tissue when they are
transplanted back into the body. Recent advances have enabled expansion
of intestinal epithelial stem cells in culture dishes, which means that
the first technical barrier has been well overcome. However, the next
step, i.e., assessment of the feasibility of intestinal epithelial stem
cell transplantation, has not yet been well established. The research
team led by Prof. Nakamura has previously reported that cultured colonic
stem cells are able to regenerate functional epithelium when
transplanted onto injured colons in mice. By extending this approach,
the research team has now investigated whether cultured SI stem cells
could regenerate epithelia when transplanted, and also how they would
behave when placed in a different environment.
In their experiments, SI epithelial cells, obtained from genetically
engineered mice in which all cells are labeled by fluorescent protein,
were cultured and then used as donor cells. Meanwhile, mucosal injuries
were generated on the distal-most part of the colon in mice, and these
were used as recipients. Shortly after the intra-colonic
infusion of donor cells, it was found that they could adhere to and
cover the denuded colonic mucosa in recipients. Moreover, at later time
points, the transplanted SI cells were shown to contain all types of
terminally differentiated cells of the SI epithelium as well as the
epithelial stem cells of SI phenotype, even in the colonic milieu. In
addition, the intestinal villi, typical structures unique only to the SI
but not to colon, were clearly visible in some parts of the graft.
Together with the presence of functional Paneth cells in the
transplanted epithelia, the study concluded that cultured SI stem cells
are able to function as genuine stem cells to reconstitute normal
epithelia of SI phenotype, even after being heterotopically transplanted.
This study provides the first evidence that
cultured SI stem cells could be a source for cell therapy for various
intestinal diseases in humans. Moreover, the study highlights the
presence of epithelium-intrinsic mechanism(s) that allows adult
intestinal stem cells to maintain their identity along the
gastrointestinal tract.