Biomedical Engineering Reference
In-Depth Information
neuroprotective and trophic effects might be within the realm of possibility. It is
promising to see that adult mammalian motor pathways in acute rodent models of
MN damage can be repaired with fetal and mouse ES cells when exploiting cell types
with correct identities implanted at the appropriate time point [
115
-
117
].
Spinal muscular atrophy (SMA) is an autosomal recessive disorder representing
the second most common MN disease. Four different types of SMA are known
with SMA type I, also called Werdnig-Hoffmann disease, being the most severe
form. Mutations of the survival of motor neuron (SMN1) gene and reduced protein
expression levels are the underlying cause of SMA and severity of disease cor-
relates with the degree of muscle weakness and early infantile onset. In contrast to
ALS, MNs in the ventral horns of the spinal cord (lower MNs) are selectively
affected in SMA [
118
]. Typically, clinical symptoms such as muscle weakness,
reduced muscular tone, and progressive muscular atrophy manifest in infants. The
use of iPS cells is an attractive approach to better understand disease mechanisms
that lead to MN death in SMA patients. Ebert et al. [
42
] established iPS cell lines
from patients with type I SMA, differentiated them into MNs, and observed pro-
gressive loss of these cells in vitro. This cellular assay might be useful for
developing novel drugs or studying off-target effects of currently used compounds.
To date, there is no effective treatment for SMA and current options are supportive
in that they alleviate some disease symptoms with physical therapy and rehabil-
itaton, ventilators due to respiratory problems, and other types of continued
medical care. Similar to the inherent problems mentioned above for ALS, cell
therapy for SMA has also to consider the complex nature of motor pathways and
axonal projections. It remains to be shown if replacement of MNs, supportive cells
(e.g. glial cells) secreting neurotrophic factors, or gene therapeutic approaches can
exert beneficial effects in SMA patients.
1.7.5 Retinal Diseases
The human retina is a highly organized multilayered tissue composed of various
specific cell types (e.g. photoreceptors, interneurons, Müller glia, retinal pigment
epithelium [RPE]). Because of the limited self-repair capacity of the retina, stem cell
therapy is a very promising approach to restore visual function or prevent blindness
[
119
-
121
]. Diseases that may benefit from stem cell therapy include retinitis
pigmentosa, diabetic retinopathy, and age-dependent macular degeneration (AMD).
Progress has been made in generating RPE and photoreceptors from pluripotent stem
cells but these stepwise protocols need further optimization and standardization in
order to increase efficiency, cell purity, and safety [
122
-
124
]. Although a cell therapy
approach for highly specialized phenotypes such as photoreceptors is very chal-
lenging due to the intricate anatomical organization of the retina, these cells may
indirectly benefit from the paracrine and trophic effects imparted by stem cells [
121
].
On the other hand, direct cell replacement and functional integration of stem cell-
derived RPE is a very promising strategy. AMD is the most common cause of
