Abstract
OBJECTIVE: Ex vivo gene therapy with the use of human mesenchymal stem cells (hMSCs) and bone morphogenetic protein (BMP) genes provides a local supply of precursor cells and a supraphysiological dose of osteoinductive molecules that may promote bone formation in patients with inadequate hMSC populations because of age, osteoporosis, metastatic bone disease, iatrogenic depletion, or other metabolic derangements. This study was undertaken to evaluate the efficacy of ex vivo gene therapy with the use of hMSCs and the BMP-9 gene to promote spinal fusion in the rat. METHODS: Sixteen athymic nude rats were treated with hMSCs transduced with recombinant, replication-defective Type 5 adenovirus containing the cytomegalovirus promoter and either the BMP-9 (Ad-BMP-9) or the β-galactosidase (Ad-β-gal) gene. Ad-β-gal served as the control. Each animal received a percutaneous, paraspinal injection of 106 hMSCs transduced with 50 plaque-forming units/cell adenovirus in the lumbar region, with Ad-BMP-9 on the left and Ad-β-gal on the right. At 8 weeks postinjection, computed tomographic scans of the lumbosacral spine were obtained, and the lumbosacral spine specimens were examined histologically. RESULTS: Both computed tomographic studies and histological analysis clearly demonstrated large volumes of ectopic bone at the Ad-BMP-9-transduced hMSC injection sites, resulting in successful spinal fusion and no evidence of nerve root compression or local or systemic toxicity. The contralateral regions that were treated with Ad-β-gal-transduced hMSCs showed no evidence of osteogenesis. CONCLUSION: The results of this study suggest that hMSC and BMP-9 ex vivo gene therapy may be useful in inducing spinal fusion as well as other related procedures and certainly warrants further clinical development.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1239-1245 |
| Number of pages | 7 |
| Journal | Neurosurgery |
| Volume | 51 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1 2002 |
| Externally published | Yes |
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Keywords
- Adenoviral vector
- Bone morphogenetic protein-9
- Ex vivo gene therapy
- Human mesenchymal stem cells
- Spinal fusion
ASJC Scopus subject areas
- Clinical Neurology
- Surgery
Cite this
Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents. / Dumont, Randall J.; Dayoub, Hayan; Li, Jin Zhong; Dumont, Aaron S.; Kallmes, David F; Hankins, Gerald R.; Helm, Gregory A.; Benzel, Edward C.; Rutka, James T.; Haid, Regis W.; Fessler, Richard G.
In: Neurosurgery, Vol. 51, No. 5, 01.11.2002, p. 1239-1245.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents
AU - Dumont, Randall J.
AU - Dayoub, Hayan
AU - Li, Jin Zhong
AU - Dumont, Aaron S.
AU - Kallmes, David F
AU - Hankins, Gerald R.
AU - Helm, Gregory A.
AU - Benzel, Edward C.
AU - Rutka, James T.
AU - Haid, Regis W.
AU - Fessler, Richard G.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - OBJECTIVE: Ex vivo gene therapy with the use of human mesenchymal stem cells (hMSCs) and bone morphogenetic protein (BMP) genes provides a local supply of precursor cells and a supraphysiological dose of osteoinductive molecules that may promote bone formation in patients with inadequate hMSC populations because of age, osteoporosis, metastatic bone disease, iatrogenic depletion, or other metabolic derangements. This study was undertaken to evaluate the efficacy of ex vivo gene therapy with the use of hMSCs and the BMP-9 gene to promote spinal fusion in the rat. METHODS: Sixteen athymic nude rats were treated with hMSCs transduced with recombinant, replication-defective Type 5 adenovirus containing the cytomegalovirus promoter and either the BMP-9 (Ad-BMP-9) or the β-galactosidase (Ad-β-gal) gene. Ad-β-gal served as the control. Each animal received a percutaneous, paraspinal injection of 106 hMSCs transduced with 50 plaque-forming units/cell adenovirus in the lumbar region, with Ad-BMP-9 on the left and Ad-β-gal on the right. At 8 weeks postinjection, computed tomographic scans of the lumbosacral spine were obtained, and the lumbosacral spine specimens were examined histologically. RESULTS: Both computed tomographic studies and histological analysis clearly demonstrated large volumes of ectopic bone at the Ad-BMP-9-transduced hMSC injection sites, resulting in successful spinal fusion and no evidence of nerve root compression or local or systemic toxicity. The contralateral regions that were treated with Ad-β-gal-transduced hMSCs showed no evidence of osteogenesis. CONCLUSION: The results of this study suggest that hMSC and BMP-9 ex vivo gene therapy may be useful in inducing spinal fusion as well as other related procedures and certainly warrants further clinical development.
AB - OBJECTIVE: Ex vivo gene therapy with the use of human mesenchymal stem cells (hMSCs) and bone morphogenetic protein (BMP) genes provides a local supply of precursor cells and a supraphysiological dose of osteoinductive molecules that may promote bone formation in patients with inadequate hMSC populations because of age, osteoporosis, metastatic bone disease, iatrogenic depletion, or other metabolic derangements. This study was undertaken to evaluate the efficacy of ex vivo gene therapy with the use of hMSCs and the BMP-9 gene to promote spinal fusion in the rat. METHODS: Sixteen athymic nude rats were treated with hMSCs transduced with recombinant, replication-defective Type 5 adenovirus containing the cytomegalovirus promoter and either the BMP-9 (Ad-BMP-9) or the β-galactosidase (Ad-β-gal) gene. Ad-β-gal served as the control. Each animal received a percutaneous, paraspinal injection of 106 hMSCs transduced with 50 plaque-forming units/cell adenovirus in the lumbar region, with Ad-BMP-9 on the left and Ad-β-gal on the right. At 8 weeks postinjection, computed tomographic scans of the lumbosacral spine were obtained, and the lumbosacral spine specimens were examined histologically. RESULTS: Both computed tomographic studies and histological analysis clearly demonstrated large volumes of ectopic bone at the Ad-BMP-9-transduced hMSC injection sites, resulting in successful spinal fusion and no evidence of nerve root compression or local or systemic toxicity. The contralateral regions that were treated with Ad-β-gal-transduced hMSCs showed no evidence of osteogenesis. CONCLUSION: The results of this study suggest that hMSC and BMP-9 ex vivo gene therapy may be useful in inducing spinal fusion as well as other related procedures and certainly warrants further clinical development.
KW - Adenoviral vector
KW - Bone morphogenetic protein-9
KW - Ex vivo gene therapy
KW - Human mesenchymal stem cells
KW - Spinal fusion
UR - http://www.scopus.com/inward/record.url?scp=0036871171&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036871171&partnerID=8YFLogxK
U2 - 10.1097/00006123-200211000-00020
DO - 10.1097/00006123-200211000-00020
M3 - Article
C2 - 12383369
AN - SCOPUS:0036871171
VL - 51
SP - 1239
EP - 1245
JO - Neurosurgery
JF - Neurosurgery
SN - 0148-396X
IS - 5
ER -