(Cross-posted from Ouroboros: Research in the
biology of aging)
One major barrier to the therapeutic use of pluripotent and
totipotent cells is that by the time a patient needs them, their
body has become less able to use them. 
The stem cell niche (i.e., those factors in the tissue
microenvironment that stem cells require in order to function
normally) changes with age, and not for the better: for example,
embryonic stem cells
lose proliferative capacity when confronted with aged
niches.
This appears to be a general problem in metazoans, and is
conserved between humans and relations as distant as arthropods —
fortunately for us, because it means that the tools and genius of
the Drosophila community can be brought to bear on the
problem. In the fruit fly, age-related changes in the stem cell
niche are well-documented, especially in the reproductive system,
and the molecular players are starting to be individually
identified (see our previous post on
Dpp, this one on
BMP, unpaired and cadherins,
and this nice
review of the whole story). There are one or two tissues in
which stem cells actually become
more numerous with age, but the consensus seems to be that the
aged microenvironment is generally not beneficial for stem cells.
At least in the fly. (cont.)
But what about species nearer and dearer to us? Fortunately, the
human case is starting to be fleshed out in equally fine detail,
and the state of the art has been thoroughly and artfully reviewed
by Stefanie Dimmeler and Annarosa Leri. (The article is
open access, so the full text is available to everyone.) The
authors focus on the heart but also address more general (and less
tissue-specific) issues along the way:
Aging and Disease as Modifiers of Efficacy of Cell
Therapy
Cell therapy is a promising option for treating ischemic
diseases and heart failure. Adult stem and progenitor cells from
various sources have experimentally been shown to augment the
functional recovery after ischemia, and clinical trials have
confirmed that autologous cell therapy using bone marrow—derived or
circulating blood–derived progenitor cells is safe and provides
beneficial effects. However, aging and risk factors for coronary
artery disease affect the functional activity of the endogenous
stem/progenitor cell pools, thereby at least partially limiting the
therapeutic potential of the applied cells. In addition, age and
disease affect the tissue environment, in which the cells are
infused or injected. The present review article will summarize
current evidence for cell impairment during aging and disease but
also discuss novel approaches how to reverse the dysfunction of
cells or to refresh the target tissue. Pretreatment of cells or the
target tissue by small molecules, polymers, growth factors, or a
combination thereof may provide useful approaches for enhancement
of cell therapy for cardiovascular diseases.
The bad news about the impact of aging and disease factors on
the prospects for cell therapy is tempered with good news — the
final quarter of the piece is devoted to therapeutic strategies for
overcoming the negative effects of the aged niche, with the
ultimate goal of using stem cells even in suboptimal tissue
microenvironments — i.e., in patients who need them.
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