Human bone marrow stroma cells display certain neural characteristics and integrate in the subventricular compartment after injection into the liquor system.
Because the neural differentiation capacity of bone marrow stromal cells (BMSCs) is still a matter of controversial debate, we performed a thorough investigation into the differentiation capacity of human BMSCs and examined their therapeutic potency. BMSCs were isolated from the femur and kept in cell cultures with various cultivation protocols being applied. In standard culture conditions using a fetal calf serum-enriched medium, while not exhibiting a neural phenotype, the majority of cells expressed a variety of neuronal marker proteins as well as the astrocyte marker GFAP. Only a minority of stem cells expressed nestin, a marker for neural precursor cells. Cultivation in serum-free medium supplemented with specific growth factors resulted in a markedly higher percentage of nestin-positive cells. To establish the therapeutic potency of bone marrow-derived cells, the synthesis of neurotrophic factors such as NGF, BDNF and GDNF was analyzed under non-stimulating standard culture conditions as well as after a neural selection procedure. The therapeutic potency of BMSCs was further examined with regard to their migratory potential in vitro and after transplantation in vivo. After stereotactic engraftment into the lateral ventricle of adult rats, mesenchymal stem cells were seen to adhere to the ependymocytes and cells of the choroids plexus. Afterwards grafted cells passed through the ependymal barrier, locating in the subventricular space. Their BMSCs took up a close host graft interaction without any degenerative influence on the host cells. Furthermore, there was morphological as well as immunohistochemical evidence for a transdifferentiation within the host tissue. In addition, BMSCs could be efficiently transduced using a third-generation adenoviral vector, indicating their potential feasibility for a gene-therapeutic option.
Arnhold
Stefan
S
Department of Anatomy I, University of Cologne, Josef-Stelzmannstr. 9, D-50931 Köln, Germany. stefan.arnhold@uni-koeln.de
Klein
Helmut
H
Klinz
Franz-Josef
FJ
Absenger
Yvonne
Y
Schmidt
Annette
A
Schinköthe
Timo
T
Brixius
Klara
K
Kozlowski
Jolanta
J
Desai
Biren
B
Bloch
Wilhelm
W
Addicks
Klaus
K
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D007267:Injections; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018874:Spheroids, Cellular / Q000166:cytology; D013238:Stereotaxic Techniques; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism*; D014161:Transduction, Genetic
D005732:Gangliosides; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C062875:ganglioside A2B5