Mesenchymal Stem Cells for the Treatment of Spinal Arthrodesis: From Preclinical Research to Clinical Scenario
Table 2
Published in vivo studies in medium animal models on mesenchymal stem cells for spinal arthrodesis procedures.
Animal model
MSCs source
Other biological adjuvant
Scaffold material
Experimental time (weeks)
Spinal fusion level
Experimental design
Main outcome
Reference
Rabbit
Expanded BM from iliac crest (1.5 × 106 cells/mL)
Osteogenic medium
HA
6 weeks
L5-L6
Group 1: autograft Group 2: HA with type I collagen gel Group 3: HA and type I collagen gel with MSCs Group 4: HA and type I collagen gel with MSCs induced toward osteogenic phenotype
The fusion rates were 4/6 in group 1; 0/6 in group 2; 2/6 in group 3; and 4/5 in group 4
Group 1: autograft from iliac crest Group 2: autograft from transverse process bone graft Group 3: HA sticks and iliac bone graft Group 4: HA sticks with BM aspirate Group 5: HA sticks Group 6: HA sticks with FN and BM aspirate. Group 7: decortication only
(i) The elasticity and mechanical strength were significantly higher in group 1 than in groups 2, 4, and 5 (ii) The mechanical strength achieved in groups 3 and 6 was nearly equal to that in group 1 (iii) The mechanical strength was significantly higher in group 6 than in group 4 (iv) Histology showed intraporous osteogenesis in groups 3, 4, and 6
Expanded BM cells from iliac crest (1 × 106 cells/mL)
(i) rhBMP-2 (ii) bFGF (iii) Autograft
HA
6 weeks
L4–L5
Group 1: autograft Group 2: HA with MSCs Group 3: HA with MSCs and BMP Group 4: HA with MSCs and bFGF Group 5: HA with MSCs and BMP/bFGF
The fusion rates were 4/7 in autograft group; 0/7 in MSCs/HA group; 2/7 in MSCs/HA/BMP group; 3/7 in MSCs/HA/FGF group; and 6/7 in MSCs/HA/BMP/bFGF group
Group 1: TCP alone Group 2: TCP with MSCs Group 3: TCP with MSCs and LIPUS
(i) Significant increase in manual palpation in group 3 treated with LIPUS (86%) in comparison with groups 1 (0%) and 2 (14%) without LIPUS (ii) The bone volume of fusion mass was significantly larger in group 3 than the other two groups by quantitative computed tomographic analysis (iii) Group 3 fusion mass had a better osteointegration length between host bone and implanted composite and presented more new bone formed in the TCP implants (iv) Group 3 had osteochondral bridging, early stage of bony fusion, from histological point of view
Poly(lactide-co-glycolide) (PLGA)/HA/ type I collagen
6 weeks or 12 weeks after grafting
L4-L5
Group 1: autograft Group 2: PLGA/HA/Type I collagen with MSCs
Radiographic, computed tomography examinations, torsional loading tests, and histologic examinations showed solid fusion in 3/5 rabbits in both experimental groups at 6 weeks and 5/5 solid fusion in both groups at 12 weeks
Group 1: autograft Group 2: nHAC–PLA Group 3: autograft with nHAC–PLA Group 4: ADSCs with nHAC–PLA
(i) The rate of fusion was significantly higher in group 1 and group 4 than in group 2 and group 3 (ii) Microstructural analysis of the samples showed more new bone-like tissue formation in group 1 and group 4 than in the other two groups (iii) Mechanical properties showed that the strength and stiffness of group 1 and group 4 were much higher than those of group 2 and group 3
Bioresorbable purified fibrillar collagen and calcium phosphate ceramics containing HA and β- TCP
18 weeks
L5-L6
Group 1: HA/ β-TCP with MSCs Group 2: HA/ β-TCP
(i) In group 1 CT scanning revealed excellent fusion in 2/12 rabbits (17%), good fusion in 8/12 (66%), and fair fusion in 2/12 (17%) (ii) In group 2 a good fusion result was found in 3/12 rabbits (25%), fair fusion in 6/12 (50%), and poor fusion in 3/12 (25%)
PLGA/BCP/collagen graft and MSC/PLGA/coralline HA/collagen graft
10 weeks
L4-L5
PLGA/BCP/collagen with MSCs (on the left side) PLGA/coralline HA/collagen with MSCs (on the right side)
(i) Radiographic, CT, and bone mineral content analyses showed continuous bone bridges and fusion mass incorporated with the transverse processes (ii) Bone mineral content values were higher in MSCs/PLGA/BCP/collagen group than in MSCs/PLGA/coralline HA/collagen group
Group 1: collagen/TCP/HA Group 2: collagen/TCP/HA with MSCs Group 3: collagen/TCP/HA/ Bac-BMP-7 with MSCs
(i) In the CT results, 6/12 fused segments were observed in group 1 (50%), 8/12 in group 2 (67%), and 12/12 in group 3 (100%) (ii) The fusion rate by manual palpation was 0% (0/6) in group 1, 0% (0/6) in group 2, and 83% (5/6) in group 3 (iii) Histology showed that group 3 had more new bone and matured marrow formation
Expanded and osteogenic induced BM from iliac crest (OMSCs)
None
ACS
8 and 12 weeks
L4-L5
Group 1: ACS with OMSCs Group 2: ACS Group 3: autograft Group 4: nothing
(i) Bony fusion was evident as early as 8 weeks in groups 1 and 3 (ii) At 8 and 12 weeks, by CT and histologic analysis, new bone formation was observed in groups 1 and 3 and fibrous tissue and absence of new bone were present in groups 2 and 4 (iii) Manual palpation showed bony fusion in 40% (4/10) of rabbits in group 1, 70% (7/10) of rabbits in group 3, and 0% (0/10) of rabbits in both groups 2 and 4
Group 1: BMSCs transduced with Smad1c with Ad5 vector Group 2: BMSCs transduced with Smad1c with Ad5 vector retargeted to integrins (RGD) Group 3: BMSCs transduced with BMP-2 with Ad5 vector Group 4: BMSCs transduced with BMP-2 with Ad5 vector retargeted to integrins (RGD) Group 5: BMSCs transduced with an Ad5 vector expressing b-galactosidase
(i) The area of new bone formed in groups 1, 2, 3, and 4 was significantly greater than the area of new bone formed in group 5 (p < 0.04 for each group compared with group 5) (ii) Group 4 mediated a greater amount of new bone formation than group 3 (iii) Similarly, group 2 mediated a greater amount of new bone formation than group 1 () (iv) Group 2 mediated a greater amount of new bone formation than the other groups ()
Expanded and osteogenic induced BM from iliac crest (2 × 106)
rhBMP-2
Alginate scaffold
16 weeks
L4-L5
Group 1: autograft Group 2: alginate scaffold with MSCs Group 3: alginate scaffold with MSCs and rhBMP-2 Group 4: alginate scaffold with rhBMP-2
(i) Radiographic union of group 1 was 11/12, of group 2 8/11, of group 3 11/12, and of group 4 0/12 (ii) Manual palpation highlighted 6/6 solid fusion in group 1, 1/6 in group 2, 5/6 in group 3, and 0/6 in group 4 (iii) The mechanical analysis (failure torque) did not differ significantly between group 1 and group 3 that were both higher than group 2
Group 1: TCP Group 2: TCP with MSC Group 3: TCP with MSCs/Bac
(i) Radiographically fusion rate was detected as being 0/12 in group 1, 4/12 in group 2, and 10/12 in group 3 (ii) Manual palpation highlighted no fusions in group 1, two solid fusions in group 2, and five solid fusions in group 3
Expanded and osteogenic induced BM from iliac crest
Bioresorbable hydrogel (pluronic F27) and coralline HA
None
6 and 12 weeks
L4-L5
Group 1: Pluronic 127/HA hybrid graft with MSCs Group 2: autograft
(i) Solid fusion was achieved in 3/5 rabbits from both group 1 and 2 at 6 weeks, and solid fusion was present in 5/5 from both group at 12 weeks (ii) No differences were detected between the two groups for biomechanical analysis and from histological point of view
