55Multiple ongoing clinical trials where MSCs are being used for their trophic and
immune-modulatory effects have also been described [ 7 ].
Various routes of administration of mesenchymal stem cells have been described
in the literature including intravenous and intrathecal routes with no reported
adverse effects. Some of the recent data has also suggested that use of mesenchymal
stem cell therapy may halt progression of bulbar symptoms and respiratory paraly-
sis in ALS patients [ 8 ].
4.3.1.2 Multiple Sclerosis (MS)
MS is a chronic neurodegenerative disease characterized by relapsing and remitting
episodes of neurological symptoms. The relapsing-remitting form of MS is the most
common subtype and occurs in young patients and is characterized by T-cell medi-
ated immune response, which triggers a cascade of events, the end result of which
is demyelination and axonal damage. Due to their immune-modulatory and immune-
suppressive effects, hematopoietic stem cell therapy has been well studied in the
treatment of multiple sclerosis with best results seen in patients with active disease
of shorter duration [ 9 ].
The outcomes of treatment are also known to be partly dependent on the pre
transplant conditioning regimens with long-term progression-free survival being
better in patients who received intermediate-intensity regimens conditioning versus
high-intensity regimens [ 10 ].
In addition to hematopoietic stem cells, neural progenitor cells of mesenchymal
origin have also been found to have therapeutic effects in both stages of multiple
sclerosis in animal models due to their anti-inflammatory effect in the acute stage
and neuro regenerative properties in the chronic stage [ 11 ].
Several reports of neuromyelitis optica, another related chronic demyelinating
disease affecting the optic nerve and spinal cord being treated with umbilical cord
derived mesenchymal stem cells have also been reported [ 12 ] with improvement in
clinical course as well as resolution of active lesions as detected on MRI [ 13 ].
4.3.1.3 Alzheimer’s Disease
Alzheimer’s disease is a slowly progressive neurological disorder characterized by
loss of memory and cognitive function. Although multiple factors such as accumu-
lation of abnormal proteins such as amyloid beta and ApoE4 are involved in the
pathogenesis of Alzheimer’s disease, the final common pathway is loss of choliner-
gic neurons and synaptic connections. This predominantly affects the basal ganglia,
hippocampus and neocortical association areas of the brain. Therapies directed at
treating Alzheimer’s disease have focused on replacing and regenerating the
impaired cholinergic neurons. Neural stem cells, due to their ability to replicate and
differentiate into several different cell types such as neurons, astrocytes and oligo-
dendrocytes at transplantation sites have been studied in management of Alzheimer’s
4 Clinical Applications of Stem Cell Transplant in Treating Non-Hematologic...