193successfully generated ES-like cell lines from mouse embryonic fi broblasts and
skin fi broblasts by simply expressing four transcription factor genes encoding Oct4,
Sox2, Klf4 and c-Myc. These iPS cell lines showed similar morphology and growth
properties as ES cells and express ES cell marker genes (Takahashi and Yamanaka
2006 ). In the same way, human iPS cells which resemble human ES cells have been
generated (Lee et al. 2012 ). Generation of patient-specifi c iPS cells from somatic
cells from any individual largely solves the two major obstacles mentioned earlier.
However, the effi ciency of generation of iPS cells is still a limiting factor in therapy
due to the use of genetic manipulations for delivery of reprogramming factors, low
effi ciency of this process, slow kinetics of direct reprogramming and potential
tumorous growth; this may be improved by replacement of genetic reprogramming
factors with small molecules or other factors (Nakhaei-Rad et al. 2012 ).
9.4.3 Immune Isolation
Problems caused by limited donor supplies and permanent immunosuppressant use
can be solved by using immune-isolation technology such as encapsulated islets
(see Fig. 9.7 ) for treating severe diabetes as shown by Sakata et al. ( 2012 ). With the
use of encapsulated islets or bioartifi cial pancreas, transplanted islets can be pro-
tected from the immune system by coating with semipermeable membranes com-
posed of high polymer. Encapsulating semipermeable membranes shields the inner
islets from the recipient’s immune system along with mechanical stress while allow-
ing diffusion of glucose, oxygen, nutrients, hormone and wastes. Islets are taken
from the donor pancreas, obtained from heart- or brain-dead donors or from living
donors (for islet autotransplantation), by islet isolation. Islets are isolated by diges-
tion of the pancreas, preserved in cold preservation solution and then purifi ed. The
materials used for encapsulation must have two key properties: fi rstly, they must
provide protection from the recipient‘s immune system; secondly, they must permit
bidirectional diffusion of small molecules. Some suitable materials for encapsula-
tion include alginate, polysulfone and polyvinyl alcohol. In conclusion, encapsu-
lated islets could enable successful allogenic or xenotransplantation with large
animals, such as pigs, overcoming limited donor supplies for islet transplantation
without the need for chronic immunosuppressant administration, thus preventing
adverse side effects induced by immunosuppressants (Sakata et al. 2012 ).
9.4.4 Bioactive Scaffold and Lentivirus
Developing tissue constructs from ES cells with matrix composition and biochemi-
cal properties fi t for tissue replacement requires extensive in vitro manipulation
involving large amounts of growth factor proteins which is expensive and unstable.
The need for in vitro culture is eliminated if cell differentiation can be directed
in vivo in the absence of exogenous growth factors. In a study carried out by Brunger
9 Human Embryonic Stem Cells and Associated Clinical Concerns