Table 5.
Pre-clinical studies using amniotic membrane derivated stromal cells for bone regeneration.
| References | Animal (No. per condition and per time) | Model: Defect localization and size | Amniotic cells characteristics (n = number of cells seeded on scaffold) | Scaffold (t = culture duration before implantation) | Treatments | Evaluation methodology | Results |
|---|---|---|---|---|---|---|---|
| Mattioli et al. (2012) | Sheep (No. = 2) | Tibial defectDiameter: 3 mm | oAECs (2 × 106 cells) | Fibrin glue (Tissuecol) (no culture) | 1) Tissuecol 2) Tissuecol + oAECs |
Histology | Bone deposition was only observed in oAECs-transplanted defects after 45 days. |
| Tsuno et al. (2012) | Rat (No. = 3) | Calvarial defectDiameter: 5 mm | hAMSCs (1 × 107 cells/mL) | β-TCP (t = NS) | 1) β-TCP 2) β-TCP + hAMSCs |
Histology | hAMSCs seeded scaffold showed immature bone deposition at 6 weeks and mature bone areas at 12 weeks. |
| Barboni et al. (2013) | Sheep (No. = 3) | Sinus augmentation | oAECs (1 × 106 cells) | HA/β-TCP (t = 3 days) | 1) HA/β-TCP 2) HA/β-TCP + oAECs |
Micro-CTHistology | oAECs seeded scaffold displayed significant earlier bone formation and maturation at 45 days and induced significantly more bone deposition at 90 days. |
| Chen et al. (2014) | Mice (No. = 6) | Subcutaneous | hAMSCs (5 × 104 cells/mL) | CultiSpher S: Porcine gelatin microcarriers (t = 28–42 days) | 1) CultiSpher S+ hAMSCs (no perfusion) 2) CultiSpher S+ hAMSCs (1 week perfusion) 3) CultiSpher + hAMSCs (2 weeks perfusion) |
Micro-CTHistology | Perfusion culture system increased mineralized matrix after 6 and 12 weeks Perfusion significantly enhanced vessel density. |
| Jiawen et al. (2014) | Rat (No. = 4) | Alveolar defectSize: NS | hAECs (1.5 × 106) | β-TCP (t = 3 days) | 1) β-TCP 2) β-TCP + hAECs |
Micro-CTHistology | hAECs seeded scaffold significantly increased bone formation at 4 and 8 weeks postoperatively. hAECs seeded scaffold showed a significantly delayed macrophage response. |
| Si et al. (2015) | Mice (No. = 3) | Subcutaneous | hAECs (1.5 × 106) | β-TCP (t = 3 days) | 1) β-TCP 2) β-TCP + hBMSCs 3) β-TCP + hAFMSCs 4) β-TCP + hAECs |
HistologyImmunohisto-chemistry | No sign of mineralization in all groups 1 month after implantation. OPN and OCN were expressed at a higher level with the seeded scaffolds. |
| Rameshbabu et al. (2016) | Rabbit (No. = 5) | Osteochondral defectDiameter: 4 mmDeep: 5 mm | hAMSCs (NS) | PEMS (7 days) | 1) Empty defect 2) PEMS 3) PEMS + hAMSCs |
Histology | hAMSCs seeded scaffold seemed to induce higher bone formation and osteochondral regeneration 60 days post-implantation. |
| Jiang et al. (2020) | Rabbit (No. = 3) | Calvarial defectDiameter: 10 mm | hAMSCs (5 × 106 cells/mL) | Fibrinogen solution (NS) | 1) Fibrin gel 2) Bio-oss 3) hAMSCs 4) Bio-oss + hAMSCs |
Micro-CTHistologySequential fluorescent labeling | Bone regeneration was significantly higher in groups 3 and 4 after 4 and 12weeks. Fluorescent labeling was significantly higher in group 4 after 3, 6, and 9 weeks. Vessels-like structure are significantly higher in presence of hAMSCs. |
| Li et al. (2020) | Rat (No. = 3) | Calvarial defectDiameter: 3 mm | hAMSCs (1 × 106 cells/mL) | Fibrin (NS) | 1) Fibrin 2) Fibrin + hAMSCs |
Micro-CTHistology | hAMSCs seeded scaffold induced significantly higher bone formation after 8 weeks. |
| Datta et al. (2021) | Rabbit (No. = NS) | Tibial defectDiameter: 2.5 mmDeep: 2 mm | hAMSCs (1 × 106 cells/mL) | Hydrogel hybride (DBM + chitosan) | 1) Empty defect 2) Hydrogel 3) Hydrogel + hAMSCs |
Micro-CTHistology | Bone regeneration was significantly higher using hydrogel + hAMSCs after 4 and 8 weeks. hAMSCs seeded scaffold showed more vascular structure after 4 weeks compared to the two other groups. |
β-TCP, β-tricalcium phosphate; DBM, demineralized bone matrix; HA, hydroxyapatite; hAECs, human amniotic epithelial cells; hAMSCs, human amniotic mesenchymal stromal cells; NS, Not specified; oAECs, ovine amniotic epithelial cells; OCN, osteocalcin; OPN, osteopontin; PEMS, Placenta-derived Extracellular Matrix Sponge.