Biomedical Engineering Reference
In-Depth Information
without any risk of transformation. Third, it has to be investigated whether these cells can be
differentiated along multiple cell lineage pathways in a controllable and reproducible manner,
or whether it is even better to use these cells in an undifferentiated state. The question of
whether ASCs can be safely and effectively transplanted to an autologous or an allogeneic
host also has to be answered. Finally, it has to be examined whether ASCs can be safely
produced on a large scale according to Good Manufacturing Practice guidelines (GMP).
Since James Thomson performed the first isolation of human ESCs, their potential of
unlimited self-renewal and differentiation has led to numerous attempts to use them in drug
discovery, disease modeling, and regenerative medicine [100]. The purpose of these attempts
consists in differentiating human ESCs into hepatocytes [101, 102], cardiomycytes [103],
neurons [104], and intestinal tissue [105]. Several pluripotent and multipotent stem cell-
based therapeutics have entered clinical trials. Table 1.5 presents a few examples of thera-
peutics that have already been approved for clinical application.
The most well-known example of the use of stem cell therapy is the transplantation of
HSCs. This procedure has been practiced successfully for decades in order to treat serious
hematological diseases. In the framework of this procedure, HSCs are injected directly into the
blood of the recipient. This injection is called “bone marrow transplantation.” The stem cells
recognize their pathway through “homing,” in which chemokines play a crucial role [106, 107].
Different types of studies have indicated the potential of mesenchymal and embryonic
stem cells for undergoing similar homing into injured tissue [108-110]. However, there is still
a debate as to whether stem cells should be systemically applied or brought to the site of the
damage. Systemic application of MSCs in humans has shown beneficial effects in osteogenesis
imperfecta and graft-versus-host disease [10, 111].
It is widely accepted that cell therapy alone is not sufficient for the regeneration of large
tissue defects. Therefore, a combination of tissue engineering and the differentiated cells
from MSCs seems to be required to trigger the healing of damaged tissue [112]. In fact,
tissue engineering has already been used for the replacement of some tissues, for example
skin, bone, or fat [112, 113] .
Stem cell-based therapy, however, brings about several safety challenges that cannot be
addressed by using standard analytical procedures. A particular difficulty is the ability to
monitor biological cell distribution, since it may not be possible to distinguish the injected
cells from the host cells. The ability to track the therapeutic cells enables the assessment of
the risk of the formation of inappropriate ectopic tissue and of tumorigenesis. Moreover,
the detection of misplaced or transformed cells may necessitate the development of methods
for their removal. However, such a removal of cells is not technically possible at the moment.
Furthermore, the delivery of a cell with an unlimited renewal potential and a capacity to
differentiate into any human cell type brings about a huge safety concern that is not raised
by any other type of treatment. The finding that undifferentiated stem cells that are injected
into immunocompromised animals are capable of forming teratomas, emphasizes the
importance of addressing this safety issue in the future, and underlines the caution that is
necessary in the development of therapies based on the use of stem cells [114].
If cells contain genetic abnormalities, they could potentially develop into teratocarcinoma
[115, 116], that is tumors composed of elements of teratomas together with persisting undif-
ferentiated cells that are highly malignant [114]. Another safety issue that should be tackled
is the immunogenicity of stem cells [117]. Although there are many reports confirming the
immune privilege of human ESCs, any foreign cell that is introduced into a patient will be
subjected to immune surveillance [118]. This evidence indicates that our understanding of
stem cells is probably not yet good enough to completely evaluate the safety of these ther-
apies in a comprehensive manner. Therefore, further research on this topic is necessary.
