Ma et al. (2017)(88. Ma G, Zhao JL, Mao M, Chen J, Dong ZW, Liu YP. Scaffold-based delivery of bone marrow mesenchymal stem cell sheet fragments enhances new bone formation in vivo. J Oral Maxillofac Surg. 2017 Jan;75(1):92-104. https://doi.org/10.1016/j.joms.2016.08.014
https://doi.org/10.1016/j.joms.2016.08.0...
)
|
Group 1: BM-MSC+HA (n=8). Group 2: BM-MSC-CSF + HA (n=8). Group 3: oBM-MSC-CSF + HA (n=8). |
6 weeks |
Micro-CT
|
New bone (mm3):
|
BM-MSC + HA: ~ 360 (A) |
BM-MSC-CSF + HA: 445 ± 29.6 (B) |
oBM-MSC-CSF + HA: 510 ± 26.3 (C) |
oBM-MSC group exhibited a more mature cortical bone. |
Sun et al. (2014)(99. Sun JJ, Zheng XH, Wang LY, Liu L, Jing W, Lin YF et al. New bone formation enhanced by ADSCs overexpressing hRunx2 during mandibular distraction osteogenesis in osteoporotic rabbits. J Orthop Res. 2014 May;32(5):709-20. https://doi.org/10.1002/jor.22590
https://doi.org/10.1002/jor.22590...
)
|
Group 1: OVX rabbits + saline solution (n=6 /time point). Group 2: OVX rabbits + Adv-GFP- ADSC (n=6 /time point). Group 3: OVX rabbits + Adv-Runx2-GFP-ADSC (n=6 /time point). Group 4: sham rabbits + saline solution (n=6 /time point). |
3, 6, and 9 weeks |
i) Micro-CT
|
Bone mineral density (mg/cc) at:
|
3 weeks: |
OVX control: ~ 70 (A) |
OVX + ADSC: ~ 85 (A) |
OVX + Runx2-ADSC: ~ 145 (B) |
Sham control: ~ 250 (C) |
6 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~ 610 (A) |
Sham control: ~ 460 (B) |
9 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~ 800 (A) |
Sham control: ~ 825 (A) |
Bone volume to total volume ratio (%) at:
|
3 weeks: |
OVX control: ~ 6 (A) |
OVX + ADSC: ~ 6 (A) |
OVX + Runx2-ADSC: ~ 11 (B) |
Sham control: ~ 24 (C) |
6 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~ 55 (A) |
Sham control: ~ 42 (A) |
9 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~62 (A) |
Sham control: ~ 64 (A) |
Trabecular number (1/mm) at:
|
3 weeks: |
OVX control: ~ 0.8 (A) |
OVX + ADSC: ~ 0.8 (A) |
OVX + Runx2-ADSC: ~1.6 (B) |
Sham control: ~ 0.9 (A) |
6 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~2.4 (A) |
Sham control: ~ 1.4 (B) |
9 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~3 (A) |
Sham control: ~ 2.2 (B) |
Trabecular thickness (um) at:
|
3 weeks: |
OVX control: ~ 50 (A) |
OVX + ADSC: ~50 (A) |
OVX + Runx2-ADSC: ~70 (B) |
Sham control: ~ 80 (C) |
6 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~150 (A) |
Sham control: ~ 190 (B) |
9 weeks: (data restricted to 2 groups) |
OVX + Runx2-ADSC: ~240 (A) |
Sham control: ~ 240 (A) |
ii) Histological analysis: (data restricted to 2 groups)
|
No differences between OVX + Runx2-ADSC and sham control. |
Alkaisi et al. (2013)(1010. Alkaisi A, Ismail AR, Mutum SS, Ahmad ZA, Masudi S, Abd Razak NH. Transplantation of human dental pulp stem cells: enhance bone consolidation in mandibular distraction osteogenesis. J Oral Maxillofac Surg. 2013 Oct;71(10):1758.e1-13. https://doi.org/10.1016/j.joms.2013.05.016
https://doi.org/10.1016/j.joms.2013.05.0...
)
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Group 1: negative control (n=9). Group 2: SHED (n=9). |
2, 4, and 6 weeks |
i) Radiographic analysis
|
2 weeks: SHED group had more bone radiopacity bridging the DO gap. |
4 weeks: SHED group demonstrate bony continuity with greater radiodensity than control group. |
6 weeks: SHED group demonstrated greater radiodensity in the distraction gap than that the control group. |
ii) Histomorphometric analysis.
|
New Bone (%) at:
|
2 weeks: |
Control: 18.41 (A) |
SHED: 35.97 (B) |
4 weeks: |
Control: 31.45 (A) |
SHED: 56.69 (B) |
6 weeks: |
Control: 52.61 (A) |
SHED: 65.28 (B) |
Bone union at:
|
2 weeks: |
Control: 0.96 (A) |
SHED: 1.75 (B) |
4 weeks: |
Control: 1.58 (A) |
SHED: 2.96 (B) |
6 weeks: |
Control: 2.5 (A) |
SHED: 3.25 (B) |
Stage of bone maturity at:
|
2 weeks: |
Control: 2.25 (A) |
SHED: 3.16 (B) |
4 weeks: |
Control: 3.25 (A) |
SHED: 4.5 (B) |
6 weeks: |
Control: 3.5 (A) |
SHED: 4.66 (B) |
Zhang et al. (2012)(1111. Zhang WB, Zheng LW, Chua DT, Cheung LK. Treatment of irradiated mandibles with mesenchymal stem cells transfected with bone morphogenetic protein 2/7. J Oral Maxillofac Surg. 2012 Jul;70(7):1711-6. https://doi.org/10.1016/j.joms.2012.01.022
https://doi.org/10.1016/j.joms.2012.01.0...
)
|
Group 1: Sham-RT (n=3). Group 2: RT (n=3). Group 3: RT + BM-MSC (n=3). Group 4: RT +BMP2/7_BM-MSC (n=3). |
4 weeks |
i) Radiographic analysis
|
RT + MSC and RT + MSC_BMP-2/7_BM-MSC groups showed more cortical bone formation compared with sham-RT and RT control groups. |
ii) Micro-CT
|
Trabecular separation (mm):
|
Sham-RT: 0.99 ± 0.16 (A) |
RT: 1.00 ± 0.07 (A) |
RT + BM-MSC: 0.99 ± 0.17 (A) |
RT + BMP2/7_BM-MSC: 1.32 ± 0.17 (B) |
Trabecular thickness (mm):
|
Sham-RT: 0.12 ± 0.01 (A) |
RT: 0.12 ± 0.03 (A) |
RT + BM-MSC: 0.15 ± 0.01 (A) |
RT + BMP2/7_BM-MSC: 0.22 ± 0.02 (A) |
Number of trabeculae (1/mm):
|
Sham-RT: 0.91 ± 0.12 (A) |
RT: 0.90 ± 0.04 (A) |
RT + BM-MSC: 0.83 ± 0.04 (A) |
RT + BMP2/7_BM-MSC: 1.08 ± 0.1 (A) |
Bone volume fraction:
|
Sham-RT: 0.12 ± 0.03 (A) |
RT: 0.11 ± 0.03 (A) |
RT + BM-MSC: 0.08 ± 0.02 (A) |
RT + BMP2/7_BM-MSC: 0.12 ± 0.04 (A) |
iii) Histological analysis
|
BM-MSC and BMP2/7_BM-MSC exhibited more mature medullary and cortical bones than the control groups. |
Lai et al. (2011)(1212. Lai QG, Yuan KF, Xu X, Li DR, Li GJ, Wei FL et al. Transcription factor osterix modified bone marrow mesenchymal stem cells enhance callus formation during distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 Apr;111(4):412-9. https://doi.org/10.1016/j.tripleo.2010.05.012
https://doi.org/10.1016/j.tripleo.2010.0...
)
|
Group 1: Saline solution (n = 9 /time point). Group 2: BM-MSC (n = 9 /time point). Group 3: OSX_BM-MSC (n = 9 /time point). |
2 and 6 weeks |
i) Radiographic analysis
|
Radiodensity at:
|
2 weeks: |
Control: ~54 (A) |
BM-MSC: ~75 (B) |
OSX_BM-MSC: ~95 (C) |
6 weeks: |
Control: ~105 (A) |
BM-MSC: ~121 (B) |
OSX_BM-MSC: ~143 (C) |
ii) Histological analysis.
|
Trabecular thickness (mm) at:
|
2 weeks: |
Control: 22.89 ± 1.96 (A) |
BM-MSC: 26.96 ± 3.23 (B) |
OSX_BM-MSC: 39.39 ± 3.54 (C) |
6 weeks: |
Control: 34.69 ±3.73 (A) |
BM-MSC: 42.41 ± 2.34 (B) |
OSX_BM-MSC: 54.21 ± 2.38 (C) |
Newly formed cortical bone area (%)at:
|
2 weeks: |
Control: 44.53 ± 5.43 (A) |
BM-MSC: 52.43 ± 2.74 (B) |
OSX_BM-MSC: 61.62 ± 3.10 (C) |
6 weeks: |
Control: 84.42 ±3.06 (A) |
BM-MSC: 90.26 ± 2.12 (B) |
OSX_BM-MSC: 97.32 ± 2.65 (C) |
Cancellous bone area (%) at:
|
2 weeks: |
Control: 24.54 ± 3.22 (A) |
BM-MSC: 33.85 ± 3.49 (B) |
OSX_BM-MSC: 42.45 ± 2.98 (C) |
6 weeks: |
Control: 42.05 ±3.58 (A) |
BM-MSC: 53.80 ± 2.91 (B) |
OSX_BM-MSC: 67.75 ± 4.04 (C) |
Jiang et al. (2010)(1414. Jiang X, Zou S, Ye B, Zhu S, Liu Y, Hu J. bFGF-Modified BMMSCs enhance bone regeneration following distraction osteogenesis in rabbits. Bone. 2010 Apr;46(4):1156-61. https://doi.org/10.1016/j.bone.2009.12.017
https://doi.org/10.1016/j.bone.2009.12.0...
)
|
Group 1: Saline solution (n = 14). Group 2: Ad5_BM-MSC (n = 14). Group 3: Ad5_bFGF BM-MSC (n =1 4). |
8 weeks |
i) DXA analysis
|
Bone mineral density (g/cm2):
|
Control: ~0.23 (A) |
Ad5_BM-MSC: ~0.25 (B) |
Ad5_bFGF BM-MSC: ~ 0.27 (C) |
Bone mineral content (g): |
Control: ~0.21 (A) |
Adv5_BM-MSC: ~0.23 (B) |
Ad5_bFGF BM-MSC: ~0.25 (C) |
ii) Micro-CT
|
Bone volume to total volume ratio (%):
|
Control: 56.00 ± 3.72 (A) |
Adv5_BM-MSC: ~ 61.6 (B) |
Ad5_bFGF BM-MSC: ~67.2 (C) |
Connectivity density (mm3):
|
Control: 11.05 ± 1.73 (A) |
Adv5_BM-MSC: ~ 13.26 (B) |
Ad5_bFGF BM-MSC: ~ 21.00 (C) |
Trabecular thickness (mm):
|
Control: 0.21 ± 0.04 (A) |
Adv5 BM-MSC: ~ 0.30 (B) |
Ad5-bFGF BM-MSC: ~ 0,38 (C) |
Trabecular separation (mm):
|
Control: 0.32 ± 0.03 (A) |
Adv5_BM-MSC: ~ 0.32 (AB) |
Ad5_bFGF BM-MSC: ~ 0,36 (B) |
Trabecular number:
|
Control: 2.01 ± 0.39 (A) |
Adv5_BM-MSC: ~ 2.60 (B) |
Ad5_bFGF BM-MSC: 3.28 (C) |
iii) Histological analysis (data restricted to half of the samples).
|
While only disordered tiny trabeculae were sporadically found in the distraction gaps of group 1, the distraction gaps in group 3 were completely bridged with mature and regular trabecular bone. Bone trabeculae only partially filled distracted gaps in group 2. |
Kinoshita et al. (2008)(1515. Kinoshita K, Hibi H, Yamada Y, Ueda M. Promoted new bone formation in maxillary distraction osteogenesis using a tissue-engineered osteogenic material. J Craniofac Surg. 2008 Jan;19(1):80-7. https://doi.org/10.1010.1097/scs.0b013e31815c93e316/j.bone.2009.12.017
https://doi.org/10.1010.1097/scs.0b013e3...
)
|
Group 1: PRP (n = 6 defects). Group 2: Saline solution -contralateral internal control for group 1 (n = 6 defects). Group 3: oBM-MSC + PRP (n = 6 defects). Group 4: Saline solution - contralateral internal control for group 3 (n = 6 defects). |
2,3 and 4 weeks |
i) Radiographic analysis
|
Radiodensity (mm AI) at:
|
2 weeks: |
Ratio PRP/saline control: ~ 0.8 (A) |
Ratio BM-MSC + PRP/saline control: ~ 1.07 (B) |
3 weeks: |
Ratio PRP/saline control: ~0.7 (A) |
Ratio BM-MSC + PRP/saline control: ~1.09 (B) |
4 weeks: |
Ratio PRP/saline control: ~0.6 (A) |
Ratio BM-MSC + PRP/saline control ~1.1 (B) |
ii) Histological analysis (data restricted to week 4)
|
New bone (%): |
Ratio PRP/saline control: ~1.2 (A) |
Ratio BM-MSC + PRP/saline control: ~1.6 (B) |
Bony content in the newly formed bone (%): |
Ratio PRP/saline control: ~0.95 (A) |
Ratio BM-MSC + PRP/saline control: ~1.2 (B) |
Hu et al. (2007)(1313. Hu J, Qi MC, Zou SJ, Li JH, Luo E. Callus formation enhanced by BMP-7 ex vivo gene therapy during distraction osteogenesis in rats. J Orthop Res. 2007 Feb;25(2):241-51. https://doi.org/10.1002/jor.20288
https://doi.org/10.1002/jor.20288...
)
|
Group 1: Saline solution (n = 9 /time point). Group 2: pEGFP-BM-MSC (n = 9 /time point). Group 3: pEGFP-BMP-2_BM-MSC (n = 9 /time point). |
2 and 6 weeks |
i) Radiographic analysis
|
Radiodensity
|
2 weeks: |
Control: ~52 (A) |
BM-MSC: ~58 (B) |
BMP-7 BM-MSC: ~70 (C) |
6 weeks: |
Control: ~99 (A) |
BM-MSC: ~113 (B) |
BMP-2_BM-MSC: ~135 (C) |
ii) Histomorphometric analysis
|
Newly formed cortical bone area (%) at:
|
2 weeks |
Control: 43.52 ± 6.11 (A) |
BM-MSC: 51.28 ± 3.85 (B) |
BMP-2_BM-MSC: 60.59 ± 4.00 (C) |
6 weeks |
Control: 82.66 ± 2.06 (A) |
BM-MSC: 89.30 ± 1.95 (B) |
BMP-2: 95.54 ± 2.07 (C) |
Cancellous bone area (%) at:
|
2 weeks |
Control: 23.69 ± 2.60 (A) |
BM-MSC: 32.22 ± 4.22 (B) |
BMP-2_BM-MSC: 41.54 ± 3.01 (C) |
6 weeks |
Control: 41.46 ± 4.01 (A) |
BM-MSC: 52.47 ± 1.93 (B) |
BMP-2_BM-MSC: 66.33 ± 4.00 (C) |
Trabecular thickness (mm) at:
|
2 weeks: |
Control: 21.13 ± 1.05 (A) |
BM-MSC: 25.43 ± 2.10 (B) |
BMP-2_BM-MSC: 37.32 ± 3.39 (C) |
6 weeks: |
Control: 32.45 ± 4.33 (A) |
BM-MSC: 40.97 ± 2.52 (B) |
BMP-2_BM-MSC: 52.32 ± 3.12 (C) |
Qi et al. (2006)(1616. Qi M, Hu J, Zou S, Zhou H, Han L. Mandibular distraction osteogenesis enhanced by bone marrow mesenchymal stem cells in rats. J Craniomaxillofac Surg. 2006 Jul;34(5):283-9. https://doi.org/10.1016/j.jcms.2006.02.002
https://doi.org/10.1016/j.jcms.2006.02.0...
)
|
Group 1: Saline solution (n = 10/time point). Group 2: BM-MSC (n = 10/time point). |
Day 27 and 55 |
i) Radiographic analysis
|
Radiodensity at:
|
Day 27: |
Control: 169 (A) |
BM-MSC: 203 (B) |
Day 55: |
Control: 221 (A) |
BM-MSC: 255 (B) |
ii) Histomorphometric analysis |
Newly formed bone volume in the cortical bone area (%) at:
|
Day 27: |
Control: 38.52 ± 3.25 (A) |
BM-MSC: 54.28 ± 3.50 (B) |
Day 55: |
Control: 85.48 ± 4.69 (A) |
BM-MSC: 92.30 ± 1.95 (B) |
Newly formed bone volume at the cancelous bone area (%) at:
|
Day 27: |
Control: 23.29 ± 3.60 (A) |
BM-MSC: 34.02 ± 3.21 (B) |
Day 55: |
Control: 41.46 ±4.01 (A) |
BM-MSC: 53.47 ± 1.83 (B) |
Trabecular thickness (mm) at:
|
Day 27: |
Control: 23.13 ± 4.31 (A) |
BM-MSC: 30.40 ± 2.17 (B) |
Day 55: |
Control: 33.31 ± 3.55 (A) |
BM-MSC: 45.97 ± 3.52 (B) |