Appendix K. 
315 
differentiated into cardiac and skeletal muscle, bone marrow stromal 
cells, fat cells, thymic epithelial cells, and cartilage cells. Analysis of 
a highly purified preparation of human mesenchymal stem cells^ 
indicated that they could proliferate extensively in culture, 
constitutively expressing the telomerase enzyme, and even after 
extensive culture retained the ability to differentiate in vitro into 
bone, fat, and cartilage cells. Isolated colonies of the cells formed 
bone when injected into inununodeficient mice. Expanding on their 
previous in vitro work with rat and human mesenchymal/stromal 
stem cells, Woodbury et ai.^^ performed molecular analyses of rat 
stromal stem cells and found that the cells express genes associated 
with all three primary germ layers — mesodermal, ectodermal, and 
endodermal — as well as a gene associated for germinal cells. The 
gene expression pattern was also seen in a clonal population of cells, 
indicating that it was not due to an initial mixed population of cells, 
but was the typical gene expression pattern of the stromal cells. The 
results suggested that the stromal stem cells were already 
multidifferentiated and that switching to a neuronal differentiation 
pattern involved quantitative regulation of existing gene expression 
patterns. Koc et al}^ have used infusion of allogeneic donor 
mesenchymal stem cells in an attempt to correct some of the skeletal 
and neurological defects associated with Hurler syndrome 
(mucopolysaccharidosis type-IH) and metachromatic leukodystrophy 
(MLD). A total of 11 patients received donor mesenchymal stem 
cells, expanded from bone marrow aspirate. Four patients showed 
significant improvements in nerve conduction velocities, and all 
patients showed maintenance or slight improvement in bone mineral 
density. 
Bone marrow-derived cells in general have shown ability to 
form many tissues in the body. For example, bone marrow-derived 
stem cells in vivo appear able to form neuronal tissues,'®’^^ and a 
single adult bone marrow stem cell can contribute to tissues as 
diverse as marrow, liver, skin, and digestive tract. One group has 
now developed a method for large-scale generation of neuronal 
precursors from whole adult rat bone marrow.®® In this procedure, 
treatment of unfractionated bone marrow in culture with epidermal 
growth factor and basic fibroblast growth factor gave rise to 
neurospheres with cells expressing neuronal markers. 
In vivo studies using fluorescence and genetic tracking of 
adult stem cells in animals, and tracking of the Y chromosome in 
humans, has shown that bone marrow stem cells cam contribute to 
numerous adult tissues. Follow-up of patients receiving adult bone 
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