Biomedical Engineering Reference
In-Depth Information
the ES cells to the level of mature endocrine cells. Afterwards, many research
groups have demonstrated the in vitro generation of insulin-producing cells from
human ES (hES) or human iPS (hiPS) cells using various modified protocols
[
117
,
119
]. However, the efficiency of these protocols is quite low with only a
small percentage of insulin or C-peptide-positive cells being developed. Further-
more, such in vitro-derived cells mostly produced insulin at a very low level or
they did not respond to glucose stimulation. Finally, very few studies were able to
show the decrease in hyperglycemia after transplantation of such in vitro-derived
cells into diabetic mouse/rat models [
120
-
122
].
To generate fully functional b cells that can mimic the physiology of normal b
cells, the existing protocols, therefore, need further refinement. On one hand, it is
important to activate various signaling cascades in a strict time-dependent fashion
to achieve a microenvironment that closely resembles the in vivo situation. On the
other hand, we need to understand the events involved in the final maturity of b
cells that takes place from late embryonic to early postnatal period, and then to
apply this knowledge to our in vitro differentiation protocols to generate b cells
that can match the physiology of normal b cells.
9.5.2.2 Adult Stem Cells to b Cells
Stem cells are also known to exist in the adult organism in many different tissues,
e.g., skin, liver, brain, bone marrow. These adult stem cells are mainly tissue
specific and therefore have a reduced plasticity compared to ES. They are involved
in tissue regeneration and repair, and under normal conditions differentiate into the
same tissue type to which they belong [
115
]. However, some of them may
differentiate into a few other cell types especially when they are cultured in vitro
under modified conditions to induce pluripotency. There are three main advantages
of using adult stem cells instead of ES cells. First of all, because of their reduced
plasticity they present a reduced risk of tumor formation following transplantation.
In case of ES cells, even a few undifferentiated cells remaining in the culture can
lead to teratocarcinoma formation in the host following transplantation. Second,
adult stem cells provide an autologous source of stem cells. Transplantation of a
tissue generated from such autologous stem cells requires no special immuno-
suppression. Finally, one critical hindrance in the use of ES is ethical consider-
ations that can be avoided by the use of adult stem cells. The potential of some
adult stem cells to generate b cells is discussed here.
Pancreatic Stem Cells
As discussed in the previous sections, neogenesis of b cells can take place in the
adult pancreas under certain physiological or pathological conditions, pointing to
the fact that a stem/progenitor cell-like population possibly resides in the pancreas.
Many possible candidates have been pointed out in the pancreas; however,
