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Monitoring Stem Cell Research 
already been used in successful treatment of patients with genetic 
disease. Bone marrow stem cells, from infants with forms of severe 
combined immunodeficiency syndrome (SCID), were removed from 
the patients, a functional gene inserted, and the engineered cells 
reintroduced to the same patients. The stem cells homed to the bone 
marrow, engrafted, and corrected the defect. 
Adult stem cells could also be used to deliver stimulatory or 
protective factors to tissues and endogenous stem cells. This would 
utilize the innate homing ability of adult stem cells, but would not 
necessarily rely on differentiation of the stem cells to participate in 
tissue replenishment. For example, Benedetti et al. utilized the 
homing capacity of neural stem cells in brain by engineering mouse 
neural stem cells with the gene for interleukin-4. Transfer into brain 
glioblastomas in mice led to the survival of most of the mice, and 
imaging analysis documented the progressive disappearance of large 
tumors.^®® Likewise, engineered mesenchymal stem cells were 
transplanted into the brains of mice that are a model of Niemann-Pick 
disease; the enzyme acid sphingomyelinase is lost in the disease, 
resulting in neurological damage and early death. The mesenchymal 
stem cells were engineered to overexpress the missing enzyme. 
When injected into brains of the mouse model, the mice showed a 
delay in onset of neurological abnormalities and an extension of 
lifespan, suggesting that the stem cells delivered and secreted the 
necessary enzyme to the brain tissue. Muscle-derived stem cells 
that were engineered to express the growth factor bone 
morphogenetic protein-2 were used to stimulate bone healing in 
mice with skull bone defects. While the muscle-derived stem cells 
did show differentiation as bone cells, the results indicated that the 
critical factor was delivery of the secreted growth factor by the stem 
cells to the areas of bone damage, allowing much more rapid healing 
than in control animals. As noted previously, neural stem cells 
show an ability to rescue degenerating neurons, including the 
dopaminergic neurons whose loss is associated with Parkinson’s 
disease. The delivery of neuroprotective substances is postulated as 
the most likely explanation for this phenomenon, rather than 
substantial differentiation by the injected neural stem cells. In 
support of this hypothesis, when neural stem cells were specifically 
engineered to overexpress a neurotrophic factor similar to glial 
derived neurotrophic factor, degeneration of dopaminergic neurons 
was prevented. 
STIMULATING ENDOGENOUS CELLS 
PRE -PUBLICATION VERSION 
