Microenvironment Design for Stem Cell Fate Determination - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 231

types [ 16 ]. Some striking examples of the therapeutic use of BM-derived MSCs
have demonstrated their great potential in a broad spectrum of clinical applica-
tions, including cardiovascular repair [ 17 ], spinal cord injury [ 18 ] and bone [ 19 ]
and cartilage repair [ 20 - 23 ].
In addition to their wide differentiation potential, MSC utilization for cell
therapy possesses several more advantages. First, these cells are easily obtained
from bone marrow aspirates and can be simply isolated from HSCs due to their
tendency to adhere to tissue culture plastic [ 15 , 23 ]. Second, although these cells
represent a very minor fraction of the total nucleated cell population in marrow, a
very large cell population may be achieved in a very short term due to their
relatively high expansion rate using standard cell culture techniques [ 22 ]. Third,
MSCs are available throughout an entire human lifetime and their utilization
would help to alleviate the problems of immune rejection and disease transmission
associated with the use of allografts [ 20 ].
MSCs are also known to reside in other adult tissues, such as adipose tissue
[ 24 ], yet they are most abundant in the BM [ 14 ]. Although stem cell niches should
by concept exist in all organs and tissues, little information exists on the nature and
the mechanisms that control these niches; and the existence of an adult stem cell
pool in some tissues (such as in pancreatic islets) is still under debate [ 25 , 26 ].
1.1.2 Embryonic and Induced Pluripotent Stem Cells
Whereas adult stem cells are mainly restricted to certain lineages, embryonic stem
cells (ESCs) can differentiate into almost any cell type. The derivation of human
ESCs (hESCs) from the inner cell mass of developing blastocysts in 1998 [ 27 , 28 ]
has opened visionary possibilities of cell therapy for almost any diseased organ.
Advances in stem cell biology have also enabled the generation of induced
pluripotent stem cells (iPSCs), following reprogramming of adult somatic cells
[ 29 , 30 ]. This has opened the possibility of generating cells from the intended
recipient of the cell therapy [ 31 ], supposedly solving the immune-rejection issue
related to ESC use, although this concept is now under debate [ 32 ]. Moreover, the
reprogrammed cells are not subjected to the same constraints of senescence that a
more mature cell population encounters, such as the ''Hayflick limit'', and the
generation of large numbers of pluripotent cells is therefore made possible. Since
iPSCs mimic the ESC cell population and do not have their own defined micro-
environment, we will refer only to the ESC microenvironment.
The microenvironment surrounding the developing embryo presents a number
of spatially and temporally instructive biochemical cues within a complex and
interactive milieu that guides and governs the sequential development and cell fate
decisions during embryogenesis. However, unlike the relatively known adult stem
cell microenvironment, the one surrounding the developing embryo is relatively
obscure. This has not prevented researchers from testing the use of synthetic
microenvironment analogs.