Biomedical Engineering Reference
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nonunion received a relatively constant volume of concentrated bone marrow. The
number of progenitor cells transplanted was estimated by counting the CFU-F. The
volume of mineralized bone formation was determined by comparing preoperative
computerized tomography scans with scans performed 4 months following the
injection. According to their findings, there was a positive correlation between the
volume of mineralized callus at 4 months and the number and concentration of
CFU-F in the graft. There was a negative correlation between the time needed to
obtain union and the concentration of FCF-U in the graft [ 111 ].
7.9.6 Osteogenesis Imperfecta
OI is a group of inherited heterogeneous disorders of the connective tissue in
which production of collagen I is defective. The clinical outcome of the diseases
ranges from no clinical signs to short stature, mobility impairments, severe skeletal
deformities, and death. In OI, fracture may occur in any bone, however, it is more
common in the extremities [ 112 ].
A routine treatment for OI is bisphosphonate, which results in increased bone
mass and reduction of fracture frequency. MSC therapy would be another option.
In this context, Horwitz et al. were the first to use marrow cell potential for treating
three children with OI. They transplanted allogeneic bone marrow. Three months
after cell engraftment, representative specimens of trabecular bone showed his-
tologic changes indicative of new dense bone formation. In addition, all patients
had increased total body bone mineral content compared with predicted values for
healthy children with similar changes in weight [ 113 ]. Another clinical trial by the
same group confirmed the effectiveness of MSC transplantation [ 114 ]. As further
evidence for the usefulness of stem cell transplantation in treating OI, a report by
Panaroni et al. was interesting. They have shown that intrauterine transplantation
of adult stem cells resulted in 20 % more synthesis of collagen I in a murine OI
model [ 115 ].
7.9.7 Hypophosphatasia
Hypophosphatasia, sometimes considered to be a fatal metabolic bone disorder, is an
inherited disease characterized by defective bone and teeth mineralization, and
deficiency of serum and bone alkaline phosphatase activity. This disorder is due to a
mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNAP)
[ 116 ]. Some researchers have attempted to use MSCs in treating hypophosphatasia.
Tadokoro et al. have used MSCs to cure an 8-month-old infant. MSCs were
obtained by culture expansion of fresh marrow from the patient's father. Some of
the MSCs were further cultured under osteogenic conditions on a culture dish or
porous hydroxyapatite ceramics, resulting in cultured osteoblasts, and osteogenic
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