Comparison of human mesenchymal stem cells derived from adipose tissue and bone marrow for ex vivo gene therapy in rat spinal fusion model.
METHODS
Rat spinal fusion model.


OBJECTIVE
To compare the efficacy of human adipose tissue-derived mesenchymal stem cells (HATDMSCs) and human bone marrow-derived mesenchymal stem cells (HBMDMSCs) transduced with an adenovirus containing the cDNA for bone morphogenetic proteins (BMP)-2 for inducing spinal fusion in an athymic rat model.


BACKGROUND
Recombinant BMPs have successfully induced spinal fusion in clinical trials. However, large doses are required for adequate bone repair. Regional gene therapy may deliver proteins to specific anatomic sites more efficiently. Gene transfer techniques using HATDMSCs have recently been tested.


METHODS
Spinal fusion was performed in rats with different treatments: Group I (n = 10) collagen sponge containing HATDMSCs transfected with adeno-BMP-2, Group II (n = 10) collagen sponge containing HBMDMSCs transfected with adeno-BMP-2, Group III (n = 10) collagen sponge containing recombinant BMP-2 (10 mug), Group IV (n = 6) collagen sponge containing HATDMSCs transfected with adeno-LacZ, Group V (n = 6) collagen sponge containing HBMDMSCs transfected with adeno-LacZ, and Group VI (n = 6) collagen sponge alone. Radiographs were obtained at 4, 6, and 8 weeks. After sacrifice, the rat spines were assessed by manual palpation, microcomputed tomography, and histologic analysis.


RESULTS
At 8 weeks, spinal fusion was observed in all Groups I, II, and III rats. 75% (15 of 20) of the gene therapy treatment animals (Groups I and II rats) had spontaneous extension of the fusion to a second level. No Groups IV, V, and VI rats developed fusion. New bone volume was significantly greater in Groups I and II than in Group VI.


CONCLUSIONS
HATDMSCs transfected with adeno-BMP-2 induce abundant bone formation and have a similar posterolateral spinal fusion in rats as similarly genetically modified HBMDMSCs. Both are potential strategies for spinal fusion and may be a more efficient method of obtaining spinal fusion over currently used grafting substances.
Miyazaki
Masashi
M
Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, California, USA.
Zuk
Patricia A
PA
Zou
Jun
J
Yoon
Seung Hwan
SH
Wei
Feng
F
Morishita
Yuichiro
Y
Sintuu
Chananit
C
Wang
Jeffrey C
JC
D000256:Adenoviridae / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D011859:Radiography; D051381:Rats; D011923:Rats, Nude; D011994:Recombinant Proteins; D013123:Spinal Fusion / Q000379:methods*; D033581:Stem Cell Transplantation; D014161:Transduction, Genetic / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta