Biomedical Engineering Reference
In-Depth Information
regeneration and repair, thus requiring augmentation by stem cell transplantation to
improve clinical outcomes.
Stem cells are immature cells that possess the ability to self-renew and to differen-
tiate into various cell types. They can be broadly classified into three categories based
on their capacity for differentiation. Totipotent stem cells, such as the zygote or cells
from early embryos (1-3 days post fertilisation), have the ability for each cell to
develop into a complete individual. Pluripotent stem cells can form all three germ
layers of the body (endoderm, mesoderm and ectoderm), an example of which are
embryonic stem cells (ESC) isolated from the inner cell mass of blastocyst (5-14
days). Multipotent stem cells are committed cells that can still form a number of
other tissues, but not all three germ layers. An example of a multipotent stem cell
is the haemopoietic stem cell which can derive both lymphoid and myeloid lineage
blood cell types.
Recent developments in the understanding of multipotent stem cells from
non-embryonic sources have sparked renewed excitement in this field. Multipotent
cells, such as the mesenchymal stem cells (MSC), appear to possess greater plas-
ticity than dictated by established paradigms of embryonic development (Phinney
and Prockop
2007
). As MSC can differentiate from primitive cells into mature cell
types, they can be used for cell replacement therapy, tissue engineering, regenerative
medicine and as vehicles for gene therapy (Gafni et al.
2004
). Unlike ESC which are
generated with difficulty and only with the sacrifice of human embryos, multipotent
cells from adult or discarded fetal-placental tissue are subject to fewer practical and
ethical issues. These attributes of multipotent cells render them promising candidates
for future clinical use.
Several clinical trials are underway for the treatment of various diseases such
as ischemic stroke (Bang et al.
2005
), skeletal dysplasia (Horwitz et al.
2001
),
spinal cord injury (Callera and de Melo
2007
) and myocardial infarction (Meyer
et al.
2006
). The key determinants for the translation of such therapies are safety
and efficacy. While the therapeutic capability of cell therapy is under investigation,
detecting the location of transplanted cells is critical to the evaluation of transplan-
tation route, timing, dosage and cell type. Temporal and spatial information on the
cells informs their engraftment efficiency and functional capacity, facilitating
the monitoring and optimising of the therapeutic process in patients. When applied
to animal experimentation, serial
in vivo
tracking of cells, as opposed to sacrificing
animals at several cross sectional time points for histology, improves the reliability
of results while reducing animal numbers.
2
In Vivo
Imaging Modalities
A number of cellular imaging modalities are under investigation, but only a few
are clinically relevant (see Table
1
) (Arbab and Frank
2008
). Clinical translation
requires a modality that provides sufficient imaging resolution and depth of
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