Effect of gabapentin-lactam and gamma-aminobutyric acid/lactam analogs on proliferation and phenotype of ovine mesenchymal stem cells.
OBJECTIVE
Classic tissue engineering consists of three components: scaffold, cells, and growth or differentiation factors. Currently, expensive bone morphogenetic proteins are the most common substance used for hard tissue regeneration. An alternative could be gamma-aminobutyric acid/lactam (GABA-lactam) analogs.


METHODS
The effects of gabapentin-lactam, cis- and trans-8-tertbutyl-GABA-pentinlactam (trans-TB-GBP-L), and phenyl-GABA-lactam were tested in this study on ovine mesenchymal stem cell (MSC) proliferation. MSCs were selected from bone marrow aspirate concentrate by plastic adherence and amplified. Aliquots of the cells were incubated in medium, with four different concentrations of the GABA-lactam analogs dissolved in dimethyl sulfoxide. Cells in medium with and without dimethyl sulfoxide served as controls. Cell proliferation was tested with a nonradioactive assay. Before and after GABA-lactam analog influence, the MSC character was evaluated by the ability of the cells to differentiate into osteoblasts, chondrocytes, and adipocytes.


RESULTS
Proliferation was significantly increased under the influence of the analogs, depending on their concentration. MSCs cultured in 1 nmol/L trans-TB-GBP-L showed the highest proliferation rate. The MSC character was not altered.


CONCLUSIONS
GABA-lactam analogs could be suited to stimulate MSC proliferation for tissue engineering applications. Further in vivo studies are necessary to evaluate the possible clinical potential of GABA-lactam analogs for hard tissue regeneration.
Sebastian
S
Sauerbier
Ralf
R
Gutwald
Margit
M
Wiedmann-Al-Ahmad
Martin
M
Wolkewitz
Jörg
J
Haberstroh
Julia
J
Obermeyer
Arne
A
Kuenz
Helene
H
Betz
Franziska
F
Wolter
Fabian
F
Duttenhoefer
Rainer
R
Schmelzeisen
Heiner
H
Nagursky
Susanne
S
Proksch
Ali
A
Al-Ahmad
D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010641:Phenotype; D012756:Sheep; D013141:Spiro Compounds / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D001372:Aza Compounds; D003470:Culture Media; D013141:Spiro Compounds; C404763:gabapentin-lactam; D005680:gamma-Aminobutyric Acid; C008842:4-amino-3-phenylbutyric acid; D004121:Dimethyl Sulfoxide