Biomedical Engineering Reference
In-Depth Information
To prove that the stem cells derived from BM and peripheral blood, including
hematopoietic stem cells, are indeed transformed into solid-organ-specific cells,
several conditions must be met:
1. The origin of the exogenous cell integrated into solid-organ time must be
documented by cell marking, preferably at the single-cell level.
2. Cell should be processed with a minimum of “ex vivo” manipulation (e.g., culturing)
which may make them more susceptible to crossing lineages.
3. The exogenous cells must be shown to have become an integral morphologic part
of the newly acquired tissue.
4. Transformed cells must be shown to have acquired the function of the particular
organ into which they have been integrated both by expressing organ-specific
proteins and by showing speci fi c organ function.
Organ/Tissue-specific niche (like in BM, liver, etc.) contains within the adult
stem cells, which are circulating in a very low number in the blood. Accumulating
evidence suggests that stem cells may also actively migrate/circulate in the post-
natal period of life. Stem cell trafficking/circulation may be one of the crucial
mechanisms that maintains the pool of stem cells dispersed in stem cell niches of
the same tissue that are spread throughout different anatomical areas of the body.
This phenomenon is very well described for HSC, but other TCSCs, for example,
endothelial, skeletal muscle, skeletal, or neural stem cells, are probably circu-
lating as well (
46
) .
BM is the home of migrating stem cells with not only hematopoietic stem cells
within their niches but also a small number of TCSCs, which might be the reason
why many authors think that the HSC may transdifferentiate, although we do not
have a direct proof for that. They might have plasticity, but not necessarily the
“transdifferentional potential.” What is differentiated in the tissue of injection might
be TCSC characteristic for that tissue. It has been shown that the number of these
cells is decreased with ageing (long-living and short-living mice and humans). It
would be interesting to identify genes that are responsible for tissue distribution/
expansion of TCSC. These genes could be involved in controlling the life span of
the mammals. Therefore, BM stem cells are a heterogeneous population of cells
with HSC and TCSC, the morphological and functional characteristics of which are
different from those of HSC. Their number among BMMNC is very low (1 cell per
1,000-10,000 BMMNC) within young mammals and might play a role in small
injuries. In severe injuries like heart infarct or stroke they have no possibility to
reveal their full therapeutic potential (
46
). The allocation of these cells to the dam-
aged areas depends on homing signals that may be inefficient in the presence of
some other cytokines or proteolytic enzymes that are released from damaged tissue-
associated leukocytes and macrophages. We can envision, for example, that metal-
loproteinases released from inflammatory cells may degrade SDF-1 locally, and
thus perturb homing of CXCR4 + TCSC. There is possibility that these cells while
“trapped” in BM are still in ”dormant” stage—not fully functional and need the
appropriate activation signals by unknown factors. These cells also, at least in some
