Table 1.
Published in vivo studies in small 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 |
|---|---|---|---|---|---|---|---|---|
| Ovariectomized rat | hPSCs from adipose tissue of patients with and without osteoporosis | NELL-1 | DBM/β-TCP |
4 weeks | L4-L5 |
Group 1: DBM/β-TCP with hPSCs (0.25 × 106 cells/mL) Group 2: DBM/β-TCP with hPSCs (0.75 × 106 cells/mL) Group 3: DBM/β-TCP with NELL-1 (33.3 μg/mL) Group 4: DBM/β-TCP with NELL-1 (66.6 μg/mL) Group 5: DBM/β-TCP with hPSCs/NELL-1 at the dosage of groups 1 and 3 Group 6: DBM/β-TCP with a hPSCs/NELL-1 at the dosage of groups 2 and 4 |
(i) Group 1 achieved a fusion rate of 20% (1/5), group 2 of 28.6% (2/7), groups 3 and 4 of 20% (1/5), and group 5 of 37.5% (3/8), and group 6 improved the fusion rates up to approximately 83.3% (5/6) (ii) Microcomputed tomography imaging and quantification further confirmed solid bony fusion in group 6 |
[22] |
|
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| Rat | In toto rat bone marrow from femur flush (1.1 × 107 cells/mL) |
bFGF | PEGDA-co-A6ACA hydrogels (poly(ethylene glycol)-diacrylate hydrogel (PEGDA) and N-acryloyl 6-aminocaproic acid (A6ACA)) | 2, 4, 6, and 8 weeks | L4-L5 |
Group 1: scaffold with bone marrow Group2: scaffold with bFGF Group 3: scaffold with saline solution |
(i) Radiographs showed fusion masses in 4 animals out of 7 in each group at 2 weeks. At 4 weeks, all animals showed clear evidence of hard tissue formation, with progressively increase at 6 and 8 weeks (ii) µ-CT imaging at 8 weeks revealed a 51% of mineralized hard tissue for group 3, 59% for group 2, and 54% for group 1 (iii) Manual palpation provided evidence of fusion in all groups, with no significant differences in fusion indices |
[23] |
|
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| Rat | Fresh bone marrow (BM) cells (range, 0.60 to 2.60 × 106 BM cells) | rhBMP-2 (0.006 mg/mL) |
Absorbable collagen sponge (ACS) | 8 weeks | L4-L5 |
Group 1: 2ACS with fresh BM and rhBMP-2 Group 2: 2ACS with rhBMP-2 Group 3: 1ACS with rhBMP-2 Group 4: ACS with BM Group 5: ACS alone |
(i) In group 1 BM plus rhBMP-2/ACS significantly increased the fusion rate to 89% (16/18) compared with a base fusion rate of 33% (4/12) in group 3 and 50% (6/12) in group 2 (p < 0.05) (ii) No difference in strength or stiffness was detected among group 1 and groups 2 and 3. (iii) No fusion or bone formation was observed in the rats of groups 4 and 5 |
[24] |
|
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| Rat | Expanded MSCs (3 × 106) from goat BM iliac crest lentivirally transduced to express luciferase | None | HA/β-TCP | 7 weeks | L1-L2 and L4-L5 |
Group 1: no cells Group 2: MSCs Group 3: MSCs gamma-irradiated (30 Gy) Group 4: MSCs dipped in liquid N2 |
(i) The antiluciferase immunohistochemistry showed no newly formed bone or luciferase-positive cells. (ii) Histological staining with Hematoxylin/Eosin highlighted no signs of a bone formation in any groups |
[25] |
|
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| Rat | Expanded bone marrow from rat femur (1 × 107 cell/mL) | None | Silk fibroin (SF) and mineralized silk fibroin (mSF) | 12 weeks | L4-L5 |
Group 1: SF scaffold Group 2: SF with MSCs Group 3: mSF Group 4: mSF with MSCs Group 5: autograft Group 6: sham group |
Fusion rate, bone volume, biomechanical parameters, and histological score showed no significant differences between group 4 and group 5. Group 3 was significantly greater for most parameters than group 2 | [26] |
|
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| Rat | Allogenic MSCs | None | 8 weeks | L4-L5 |
Group 1: trinity evolution (DBM with MSCs) Group 2: grafton (DBM) Group 3: DBM Group 4: decortication only |
(i) Fusion rate by radiography was 8/8 for group 1, 3/8 for group 2, and 5/8 for group 3 (ii) Fusion rate by µ-CT and manual palpation was 4/8 for group 1, 3/8 for group 2, and 3/8 for group 3 |
[27] | |
|
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| Mouse | Bone marrow from femur and tibia (1.0 × 108 cells/mL) | PRP from donor (1.0 × 109 platelets/mL) or rhBMP-2 (31 µg/mL) |
ACS | 4 weeks | L4-L5 and L5-L6 |
Group 1: collagen sponge with rhBMP-2 and saline solution Group 2: collagen sponge with rhBMP-2 and PRP Group 3: collagen sponge with rhBMP-2 and BM Group 4: decortication only |
(i) Fusion appeared radiographically and histologically similar in all three experimental groups (ii) The area, volume, and density of the fusion mass were significantly greater (p < 0.05) for group 3 as compared with group 1 (iii) Group 2 had intermediate fusion area and density (iv) No spinal fusion was detected in group 4 |
[28] |
|
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| Rat | Expanded rat bone marrow from femurs (1 × 106 cells/mL) | Fibrin matrix | PCL-TCP | 6 weeks | L4-L5 |
Group 1: 10 µg of rhBMP-2 with 1 × 106 undifferentiated BMSCs Group 2: 10 µg of rhBMP-2 with osteogenic-differentiated BMSCs Group 3: 2.5 µg rhBMP-2 with undifferentiated BMSCs Group 4: 2.5 µg rhBMP-2 with osteogenic-differentiated BMSCs Group 5: 0.5 µg rhBMP-2 with undifferentiated BMSCs Group 6: 0.5 µg rhBMP-2 with osteogenic differentiated BMSCs |
(i) Predifferentiation of BMSCs before transplantation failed to promote posterolateral spinal fusion when codelivered with low-dose of rhBMP-2 in group 5 as 17% fusion rate was observed (1/6) (ii) In contrast, combined delivery of undifferentiated BMSCs with low-dose BMP-2 (2.5 µg) as in group 5 demonstrated significantly higher fusion rate (4/6 or 67%) as well as significantly increased volume of new bone formation |
[29] |
|
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| Rat | Human bone marrow (5 × 106 MSCs) |
None | Titanium microplates with HA | 8 weeks | L1–L3 |
Group 1: titanium microplates with HA Group 2: titanium microplates with HA/MSCs |
Histology, histomorphometry, and µ-CT revealed no significant bone formation in group 2 in comparison with group 1 | [30] |
|
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| Rat | ADSCs (5 × 106 cells/scaffold) |
rhBMP-2 or adenoviral vector containing BMP-2 gene |
Type-I collagen sponge | 4 weeks | L4-L5 |
Group 1: ADSCs transduced with an adenoviral vector containing rhBMP-2 gene Group 2: ADSCs with osteogenic media and 1 mg/mL of recombinant rhBMP-2 Group 3: rhBMP-2 (10 mg) Group 4: rhBMP-2 (1 mg) Group 5: ADSCs |
(i) All animals of group 1 were characterized by fusion masses (8/8) after 4 weeks (ii) Group 1 revealed spinal fusion at the cephalad level (L3 and L4) (iii) New bone formation in groups 1 was significantly larger than those in any other treatment group (p < 0.005) (iv) Groups 3 and 4 showed a solid fusion in 8/8 and 4/8 animals, respectively (v) Groups 2 and 5 showed no fusion |
[31] |
|
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| Rat | hPSCs from adipose tissue | None | DBM | 4 weeks | L4-L5 |
Group 1: DBM Group 2: DBM with 0.15 × 106 hPSCs Group 3: DBM with 0.50 × 106 hPSCs Group 4: DBM with 1.50 × 106 hPSCs |
(i) hPSC treatment (groups 2, 3, and 4) significantly increased spinal fusion rates in comparison with group 1 (ii) Groups 2, 3, and 4 resulted in fusion rates of 100%, 80%, and 100%, respectively, compared with 20% fusion in group 1 (iii) Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion in hPSC treatment groups (iv) Histological analyses showed endochondral ossification in hPSC-treated samples |
[32] |
|
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| Rat | ADSCs from healthy donors (1.0 × 106) Purchased BMSCs (1.0 × 106) |
Adenoviral vectors adeno-BMP-2 and adeno-LacZ used to transduce ADSCs and BMSCs | ACS | 8 weeks | L4-L5 |
Group 1 ACS with ADSCs transfected with adeno-BMP-2 Group 2 ACS with BMSCs transfected with adeno-BMP-2 Group 3 ACS with rhBMP-2 Group 4 ACS with ADSCs transfected with adeno-LacZ Group 5 ACS with BMSCs transfected with adeno-LacZ, and Group 6 ACS |
(i) Spinal fusion was observed in groups 1, 2, and 3 rats (ii) 75% (15/20) of the animals of groups I and II had spontaneous extension of the fusion to a second level (iii) No animals in groups 4, 5, and 6 rats developed fusion (iv) New bone volume was significantly greater in groups 1 and 2 than in group 4 |
[33] |
|
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| Rat | Expanded BM cells from femurs and tibias (1 × 106/60 μL) |
FGF-4 (41 μg) |
HA | 8 weeks | L4-L5 |
Group 1: HA Group 2: HA with MSCs Group 3: HA with MSCs and FGF-4 |
(i) Radiographic, high-resolution μ-CT, and manual palpation revealed spinal fusion in 5/6 (83%) in group 2 (ii) In group 1, 3/6 (60%) rats developed fusion at L4-L5 by radiography and 2/5 (40%) by manual palpation in radiographic examination (iii) In group 3, bone fusion was observed in only 50% of rats by manual palpation and radiographic examination |
[34] |