Biomedical Engineering Reference
In-Depth Information
week 12, fetal stem cells (as well as the embryonic stem cells which preceded
them) can be transplanted into an individual, without being rejected. This is
because they have little to none of the immune-triggering proteins—HLA
antigens—on their surface (
16
). After the 12th week, fetal stem cells acquire
these proteins, and they remain present on stem cells from this point on, includ-
ing on adult stem cells. Thus, while some advocate therapeutic use of stem cells
derived from cord blood, adult bone marrow, or the bloodstream, these sources
pose the problem of possible rejection reactions (
17
) . Therefore, stem cells
derived from these sources may have therapeutic potential only when given to
the individual from whom they were derived (“autologous” transplantation) or
from an immunolgically matched donor (“allogenic” transplantation).
3. Cord blood stem cells
In 1988, successful transplantation occurred in a young boy with Fanconi anemia
using umbilical cord blood collected at the birth of his sibling (
18
) . The patient
remains alive and well to this date. In 1992, a patient was successfully trans-
planted with cord blood instead of bone marrow for the treatment of leukemia.
Over the past decade, the use of cord blood has expanded rapidly. Cord blood has
been used to transplant in any disease state for which bone marrow can be used
in spite of some disadvantage—rather small number of cells collected in each
unit; delayed engraftment of neutrophils is common with cord blood.
4 .
Adult stem cells
Self-regeneration is the ability of stem cells to divide and produce more stem
cells. During early development, the cell division is symmetrical, i.e., each cell
divides to give rise to daughter cells, each with the same potential. Later in
development, the cell divides asymmetrically with one of the daughter cells pro-
duced also a stem cell and the other a more differentiated cell. Here we meet the
problem with cultivation of adult stem cells since most of the media applied
induce early differentiation. Therefore, they were expanded in culture media
enriched with cytokine cocktail, and assayed before and after the expansion
either by cloning in vitro using limited dilution method in culture (
19
) or in vivo
by transferring them through NOD/SCID mice (
20
) or adoptive humanized
mouse model (
21
). All of these approaches have their advantages and disadvan-
tages and still do not satisfy the optimal needs for expansion, HLA (MSH) com-
patibility, and consecutive simple therapeutic use of adult stem cells. For that
reason, the mobilization of stem cells from intact bone marrow, for the purposes
other than bone marrow transplantation (for example in the case of myocardial
infarction or stroke as it was done by Orlic and Ratajczak in the first line),
emerged as an idea to replace the in vitro manipulation, overcome in vitro expan-
sion problems, and do the job in vivo. Unfortunately, as already mentioned, some
individuals are poor mobilizers and some of them are irresponsive, for yet
unknown reasons. And this is the limitation of otherwise splendidly designed
clinical approach. Therefore, a lot of basic research is necessary to expand this
field of stem cell application and with the better knowledge of the self-renewal
control mechanism it will largely lead to efficient improvement, e.g., control and
use of the fundamental principles for optimal expansion.
