Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice
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Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice. / Dreyer, Chris H; Kjaergaard, Kristian; Ditzel, Nicholas; Jørgensen, Niklas R; Overgaard, Søren; Ding, Ming.
In: Journal of Biomedical Materials Research. Part A, Vol. 105, No. 12, 2017, p. 3326-3332.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice
AU - Dreyer, Chris H
AU - Kjaergaard, Kristian
AU - Ditzel, Nicholas
AU - Jørgensen, Niklas R
AU - Overgaard, Søren
AU - Ding, Ming
N1 - © 2017 Wiley Periodicals, Inc.
PY - 2017
Y1 - 2017
N2 - INTRODUCTION: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation.METHODS: Twenty-eight SCID (NOD.CB17-Prkdcscid/J) mice had hydroxyapatite granules seeded with 5 × 105MSCs inserted subcutaneous. Pellets released VEGF on days 1-7, days 1-14, days 1-21, days 1-42, days 7-14, and days 21-42. After 8 weeks, the implant-bone-blocks were harvested, paraffin embedded, sectioned, and stained with both hematoxylin and eosin (HE) and immunohistochemistry for human vimentin (hVim) staining. Blood samples were collected for determination of bone-related biomarkers in serum.RESULTS: The groups with 5 × 105MSCs and VEGF stimulation on days 1-14 and days 1-21 showed more bone formation when compared to the control group of 5 × 105MSCs alone (p < 0.01). Serum biomarkers had no significant values. The hVim staining confirmed the ovine origin of the observed ectopic bone formation.CONCLUSION: Optimal bone formation of MSCs was reached when stimulating with VEGF during the first 14 or 21 days after surgery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3326-3332, 2017.
AB - INTRODUCTION: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation.METHODS: Twenty-eight SCID (NOD.CB17-Prkdcscid/J) mice had hydroxyapatite granules seeded with 5 × 105MSCs inserted subcutaneous. Pellets released VEGF on days 1-7, days 1-14, days 1-21, days 1-42, days 7-14, and days 21-42. After 8 weeks, the implant-bone-blocks were harvested, paraffin embedded, sectioned, and stained with both hematoxylin and eosin (HE) and immunohistochemistry for human vimentin (hVim) staining. Blood samples were collected for determination of bone-related biomarkers in serum.RESULTS: The groups with 5 × 105MSCs and VEGF stimulation on days 1-14 and days 1-21 showed more bone formation when compared to the control group of 5 × 105MSCs alone (p < 0.01). Serum biomarkers had no significant values. The hVim staining confirmed the ovine origin of the observed ectopic bone formation.CONCLUSION: Optimal bone formation of MSCs was reached when stimulating with VEGF during the first 14 or 21 days after surgery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3326-3332, 2017.
U2 - 10.1002/jbm.a.36195
DO - 10.1002/jbm.a.36195
M3 - Journal article
C2 - 28879669
VL - 105
SP - 3326
EP - 3332
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
SN - 1549-3296
IS - 12
ER -
ID: 194631542