Biomedical Engineering Reference
In-Depth Information
Our group has also identified myogenic endothelial cells within human skeletal
muscle. Using FACS, this population is able to be identified by the coexpression of
myogenic and endothelial cell surface markers (CD56, CD34, CD144). This
unique endothelial population, so-called myoendothelial cells, may represent
another human muscle-derived progenitor cell. Compared to myoblasts (CD56),
they demonstrate a significantly higher survival rate under hydrogen peroxide-
induced oxidative stress and display superior muscle regeneration in immunode-
ficient mice [
56
].
In addition to tissue-resident adult stem cells, two pluripotent cell types have
been considered for cell therapies: embryonic stem cells (ESCs) and induced
pluripotent stem (iPS) cells. However, due to the relatively new nature of iPS cell
technology, autologous therapies may be far off. Much more likely in the near
future is the use of iPS cells for patient-specific drug screening. In this scenario,
reprogramming a somatic cell from a patient with a particular disease would
provide disease-specific, and patient-specific, pluripotent cells. Such a pool of cells
could then be derived into any tissue of interest and used as a tool for drug
screening [
57
]. However, reprogramming is a highly inefficient process.
Comparing the reprogramming efficiency of skeletal muscle progenitors and
committed myoblasts, Tan and colleagues demonstrated the case of myogenic
cells, the efficiency of reprogramming negatively correlates with the level of
somatic cell differentiation [
58
]. Thus, in the future, the selection of stem and
progenitor cells for iPS cell generation may greatly improve upon this process. If
used for regenerative medicine, both iPS cells and ESCs would obviously need to
be differentiated down the skeletal muscle lineage prior to transplant to prevent the
formation of teratomas. Human ESCs have been differentiated into myoblasts able
to regenerate muscle in vivo. However, the process is quite inefficient [
59
].
In addition to the barriers that exist for all cell types, such as immunogenicity,
survival, and differentiation, pluripotent cells also have the additional risk of tumor
formation upon transplant [
19
]. Therefore, specific and well developed protocols
remain to be developed in order to produce fully committed cells from iPS cells
and ESCs, and verify a lack of tumorogenicity.
6.3.4 Gene Therapy
When the dystrophin gene, whose product is missing in DMD, was identified in
1987, scientists thought that a genetic approach to treatment would provide a cure
for DMD/BMD [
60
]. The delivery of a therapeutic gene to diseased tissue, the
basis of gene therapy, has had a modest level of success in treating multiple
musculoskeletal diseases. However, significant hurdles remain for gene therapy:
off target delivery, immune rejection, and mutation [
61
]. The most efficient
method of gene delivery is virus-mediated transfer. Essentially, the gene of interest
is packaged into a viral vector stripped of the endogenous genes required for
replication. In early proof-of-concept studies for gene transfer to muscle, viral
