Biomedical Engineering Reference
In-Depth Information
marrow. Furthermore, the pluripotent stem cells derived from the amniotic fluid,
placenta, and umbilical cord blood show some characteristics similar to those of
MSCs.
The MSCs residing in the bone marrow were previously believed to play only
supportive roles for hematopoiesis by expressing various cytokines, growth
factors and adhesion molecules. Cohnheim in the 19th century
18
first implied the
presence of these cells in the blood and their possible role in wound repair.
Friedenstein and his group were the first in the early 1970s to better describe
these MSC in a number of species, including mice, rats, rabbits, guinea pigs,
hamsters and humans, showing their differentiation potential into cells of
mesenchymal lineage including chrondrocytes, osteoblasts, myocytes and
adipocytes.
19±21
Because these cells appeared clonal in nature, they were
initially termed colony-forming unit fibroblasts (CFU-F). Isolation of MSC was
then undertaken by Caplan who described a technique still used today by
isolating the cells that adhered to the bottom of the plates when the bone marrow
cells are cultured in vitro.
22
Furthermore, several in vivo and in vitro studies
have confirmed the pluripotent potential of these cells and have observed the
presence of injected MSC in host adipose tissue, lung, cartilage, central nervous
system, liver, spleen, thymus and skeletal muscle.
23±28
In the last few years,
studies have also shown the capacity of these MSC to differentiate into cells of
lineages other than mesenchymal, such as hepatocytes,
23
kidney and even early
astrocytes.
29
6.3.1 MSC characteristics and subpopulations
Although MSCs' pluripotent potential has been demonstrated in many studies,
controversy still exists as to what proportion of these cells is truly pluripotent.
Thus, although they are collectively called marrow-stromal cells, not all stromal
cells are pluripotent.
30
In fact, it was reported that up to one-third of the initial
adherent stromal colonies are truly polypotent.
31
Plating studies confirm the
rarity of MSC in the adult bone marrow, representing approximately 0.01% to
0.05% of the nucleated cells, being much less abundant than their hematopoietic
counterpart.
32
Nonetheless both cell types appear to contribute to myocardial
repair.
The human MSC can be cloned and expanded to greater than 1 million-fold
and still retain the ability to differentiate into several mesenchymal lineages.
After isolating human MSC from over 600 patients, Pittenger and his coworkers
have shown that these cells behaved as a homogeneous population, and retained
their multilineage potential for several passages, although not indefinitely.
31
Unlike hematopoietic cells, MSC are CD34ÿ and CD45ÿ. Although still not
fully identified, some other characteristic MSC surface markers include CD29,
CD44, CD71, CD90, CD106, CD120a, CD124, SH2, SH3 and SH4-69 (Table
6.1). It is important to keep in mind that this is an incomplete list, and as
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