Biomedical Engineering Reference
In-Depth Information
embryos, even without adding the hematopoietic growth factor [56]. Several scientists
have demonstrated that, at earlier developmental stages, HSCs from different tissues have
a great ability of self-replication, show different homing and surface characteristics, and
are less likely to be rejected by the immune system. Therefore, they could be used for
therapeutic transplantation [57].
Further studies have shown that there are two types of HSCs: long- and short-term HSCs.
Long-term HSCs proliferate during their entire lifetime. It has been demonstrated that in
young adult mice, 8-10% of these HSCs enter the cell cycle and divide every day. Short-term
HSCs proliferate only for a limited time. Long-term HSCs have a higher telomerase activity
than their short-term counterparts [58].
Active telomerase is a feature of dividing, undifferentiated cells and is also found in cancer
cells. In mice, only 1 in every 10,000-15,000 bone-marrow cells is considered to be a long-term
HSC [58].
Mesenchymal Stem Cells
The existence of non-hematopoietic stem cells was suggested by Cohnheim in 1867 [59]. He
claimed that bone marrow may be the source of fibroblasts with collagen fibers that are part
of the normal wound-healing process [60].
In 1974, Friedenstein and his colleagues performed the first isolation of MSCs from bone
marrow. They reported that the adherent cells (the non-adherent cells were HSCs that were
removed 4 h after the cells had been seeded on plastic culture dishes) had a heterogeneous
appearance, but that most of them were spindle-shaped and formed foci of two to four cells,
which remained inactive for 2-4 days and then began to grow rapidly. They also demon-
strated that these cells were able to differentiate into colonies that had some similarities to
bone and cartilage. Further studies extended Friedenstein's observations and demonstrated
that these cells were multipotent and able to differentiate into osteoblasts, chondrocytes,
adipocytes, and even into myoblasts. They are currently referred to as mesenchymal stem
cells or marrow stromal cells [61].
Sources of MSCs
Mesenchymal stem cells have the potential to differentiate into chondrocytes, osteoblasts,
adipocytes, fibroblasts, marrow stromal cells, and other tissues of mesenchymal origin. The
MSCs have various origins and the ability to regenerate specific cell types for several tissues,
for example adipose tissue, periosteum synovial membrane, muscle, dermis blood, bone
marrow, and teeth. Bone marrow stroma is considered to be the source of a large amount of
multipotent cells that have access to various tissues via the blood circulation. It has been
established that MSCs from bone marrow stroma are capable of differentiating into adipo-
cytes, osteoblasts, chondrocytes, and also into hematopoiesis supporting stromal cells. The
differentiation of MSCs into adipocytes, osteoblasts, and chondrocytes can be significantly
increased by the use of specific differentiation cocktails [13, 17] (Figure 1.2).
Although BMSCs are an option for stem-cell therapies, their use is still subject to some
limitations: first, a bone marrow harvest is a painful procedure; second, although MSCs
grow well under standard tissue culture conditions,
ex vivo
expansion is necessary due to the
relatively low numbers of MSCs that are present in the harvested marrow. Therefore, and
since obesity is becoming increasingly widespread in industrialized countries, adipose tissue
has become an attractive alternative source of stem cells for clinical and nonclinical applica-
tions [62]. Moreover, adipose tissue yields a much higher amount of MSCs than bone
