Artificial Scaffolds and Mesenchymal Stem Cells for Hard Tissues - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 158

discussed as supplements for treating diabetes [ 11 ], muscular dystrophy [ 12 ],
spinal injuries [ 13 ], retinal degeneration [ 14 ], liver damages [ 15 , 16 ], as well as
Parkinson's disease [ 17 ] and Alzheimer's disease [ 18 , 19 ], among others. All in all,
SCs provide an invaluable resource for patient-specific therapies in a variety of
diseases in the future.
On the other hand, several obstacles have to be overcome before a safe and
efficient treatment of patients is warranted. One hurdle is to force the cells with
normal growth in cell culture in a monolayer to spread into the third dimension.
A number of studies have investigated the use of SCs in combination with scaffold
materials and growth factors to replace, for example, lost or damaged bone [ 20 , 21 ].
This will be discussed below. Another problem is that the developmental fate of
SCs seems to be guided, but not restricted, by the surrounding tissue and the
application of undifferentiated SCs contains the risk of spontaneous differentiation
into undesirable cell types. It has been demonstrated that transplanted bone mar-
row-derived SCs can spontaneously differentiate into the osteogenic lineage when
applied to the heart [ 22 ]. To exclude tumor formation from undifferentiated SCs
and differentiation into undesired cell types, it is absolutely fundamental to opti-
mize the control of differentiation. An overview of the current status with further
particulars is given below.
2.1.1 Embryonic SCs
Pluripotent embryonic stem cells (ESCs) are isolated from the inner cell mass of
the blastocyst [ 23 ]. The high differentiation potential of ESCs gives rise to huge
expectations for cell-based therapies in regenerative medicine (see Fig. 1 ).
However, the isolation and subsequent use of SCs derived from a human
embryo brings about strong ethical concerns [ 24 ] and is strictly limited by law in
most countries. These cells are therefore mainly used in approaches where other
SCs have limitations, such as in differentiation towards the neuronal lineages [ 25 ]
or towards tissue cells where no SCs have been found to date. The application of
ESCs in bone replacement is rather limited and focuses on basic research for a
better understanding of the neural regulation of bone, the marrow, and its specific
microenvironment (for a review, see [ 26 ]).
2.1.2 Induced Pluripotent SCs
A new type of pluripotent SCs has been developed recently, which seem to be an
alternative to ESCs without ethical issues, the so-called induced pluripotent stem
cells (iPS). These iPS can be obtained from an adult individual by the genetic
reprogramming of fully differentiated somatic cells using a set of four specific tran-
scription factors, such as Oct4, Sox2, Klf4, and c-Myc [ 27 - 29 ] or Oct4, Sox2, Lin28,
and Nanog [ 30 ] (see Fig. 2 ). Shortly after the first reports on iPS, the transcription
factor set used was reduced and the methods have been altered and improved.