Table 1 Summary of studies related to the application of MSC sheets for the regeneration of the calvarial, mandible, and maxillary bone defects
From: Application of mesenchymal stem cell sheet for regeneration of craniomaxillofacial bone defects
Region of defect | Defect size | Animal | Construct | In vitro culturing time of sheet formation | Ascorbic acid | Dex | Harvesting or transferring method | Post-implantation time | In vivo tests for cell sheet evaluation | References |
|---|---|---|---|---|---|---|---|---|---|---|
Cranium | 8 mm diameter (CSD) | 8-week-old female Sprague Dawley rats | Human ES-MSC sheets | 7 days with Vitamin C and osteogenic inductive medium | 100 mg/mL | – | A sterile forceps (physical harvesting) | 8 weeks | – Micro-CT – Sequential fluorescent Labeling – Histological and histomorphometric observation – Immunohistochemistry | [5] |
Cranium | 15 mm diameter (CSD) | 3- to 5-month-old New Zealand rabbits | BM-MSC sheets + nano-HA + PRF | 14 days | 50 µg/ml | 10 nM | A cell scraper (physical harvesting) | 8 weeks | – Histological and histomorphometric analysis – 3D Computerized tomography | [1] |
Cranium | 15 mm diameter (CSD) | 3-month-old New Zealand rabbits | BM-MSC sheets | 14 days | 50 µg /ml | 10 nM | A cell scraper (physical harvesting) | 8 weeks | – Micro-CT analysis – Histological analysis of bone – Van Gieson staining | [76] |
Cranium | 15 mm diameter (CSD) | Adult New Zealand rabbits | BM-MSC sheets + demineralized bone matrix | 14 days | 50 µg/mL | 100 nM | A cell scraper (physical harvesting) | 6 and 12 weeks | – Radiographic analysis – H & E staining | [27] |
Cranium | 5 mm diameter (CSD) | 6-week-old male Sprague Dawley rats | Multilayer BM-MSC cell sheets + PLLA/gelatin electrospun mesh (CSMs) | Cells were cultured for 7 days to generate sheets and then four monolayer CSMs were stacked layer-by-layer and incubated for another 3 days to construct multilayer CSMs | 0.05 mM | 1 × 10−8 mM | The cell sheet was not detached because it was generated on the mesh surface | 4 and 12 weeks | – Histological analysis (H&E and Masson’s trichrome staining) – Immunohistochemical staining (OCN and OPN) – Micro-CT | [77] |
Cranium | 6.8 mm diameter | 10-week-old male F344 rats | Periosteal cell sheets | 5 days and cell sheets were detached using 0.25% Trypsin–EDTA solution and then cells were cultured for additional 10 days | – | – | Reduction of temperature below 20 °C for 30 min (physical harvesting) | 24 weeks | – Micro-CT – Histology | [78] |
Cranium | 5 mm diameter | Adult female New Zealand rabbits | Alveolar BM-MSC sheets | 10 days | 20 µg/mL | - | – | 4 and 8 weeks | – Micro-CT – Histology analysis – Immunofluorescence analysis | [79] |
Cranium | 5 mm diameter | 8-week-old male Sprague Dawley rats | AD-MSC sheets + Bone Granule Complex (with/without) Semaphorin 3A injection | 7 days | - | - | - | 4 or 8 weeks | – Micro-CT – Histomorphological analyses | [80] |
Cranium | 5 mm in diameter | 12- to 13-week-old male Sprague Dawley rats | BM-MSC sheets + PLGA/HA Scaffolds + human BMP-2 vectors | 2 weeks | - | - | A cell scraper (physical harvesting) | 4 and 8 weeks | – Micro-CT – Histological examination – qRT-PCR analysis of hBMP-2 expression | [81] |
Cranium | 1.6 mm diameter | 6- to 8-week-old male C57BL/6j or NOD/SCID mice | Human BM-MSC sheets + IFN-γ | 4 days | 50 µg/mL | - | Scratched using a micropipette tip (physical harvesting) | 7 and 28 days | – Micro-CT – Histological analysis | [56] |
Cranium | 15 mm diameter (CSD) | 3-month-old New Zealand rabbits | BM-MSC sheets + PRF | 2 weeks | 50 mg/mL | - | A cell scraper (physical harvesting) | 8 weeks | – Micro-CT – Histological analysis | [82] |
Cranium | 10 mm diameter | 3-month-old New Zealand rabbits | AD-MSC sheets + endothelial progenitor cells | 2 weeks | 50 mg/mL | 100 nM | ND | 8 weeks | – Micro-CT – Histological analysis | [24] |
Cranium | 8 mm diameter | Female Wistar rats | Differentiated rBM-MSC sheets + Porous β-TCP scaffolds | 14 days + 7 other days incubation with induced endothelial-like cells | 50 mg/mL | – | – | 2, 4, and 8 weeks | – X-ray – Micro-CT – Histological analysis – Immunohistochemistry staining | [59] |
Osteogenic cell sheet + Porous β-TCP scaffolds | 21 days | 50 mg/mL | 10 nM | |||||||
Mandible | 5 mm diameter | Beagle dogs | AD-MSC sheets | 1 week | 82 µg/mL | – | By reducing the room temperature to (physical harvesting) | 6 weeks | – Micro-CT – Photographic image analysis – Immunohistochemical analysis – Histological analysis | [11] |
Mandible | Vertical osteotomies (the authors did not give exact size) | 6- and 8-month-old Male New Zealand rabbits | BM-MSC sheet fragments | 2 weeks | 50 g/ml | 100 nM | A cell scraper (physical harvesting) | 3 and 6 weeks after injection | – Micro-CT – Radiographic DXA examinations – Histological and Histomorphometric analyses | [52] |
Mandible | Large defect (the authors did not give exact size) | 14-month-old male mongrel dogs | PLGA scaffolds with or without BM-MSC sheets | 7–10 days | – | – | By reducing the temperature below 20˚C for 60 min (physical harvesting) | 4, 8, 12, and 16 weeks after surgery | – X-ray analyses – H & E staining – Bone hardness analysis | [53] |
|  | A trapezoid defect (the authors did not give the size) | 14- to 23-month-old mongrel dogs | PLGA with and without canine stem cell sheets after osteoblast induction | 12 days | – | – | The culture dish was placed in the calorstat for 25 min | 3, 9, and 12 weeks | – X-ray imaging – Histological observation | [83] |
| Â | Â | Â | Â | Â | Â | Â | Â | Â | Â | Mandible |
Mandible | Not given | 4-month-old female, domestic pigs | Triple-layer BM-MSC sheets | Two consecutive days of seeding, 2 other days of incubation | – | – | By reducing the temperature below 20˚C for 1 h | 6 weeks | – Micro-CT – Histological analysis – Immunohistochemical analysis | [84] |
Mandible | Not given | 15-week-old syngeneic rats | folded BM-MSC sheets with an average diameter of 2 mm | Until reaching confluence | 0.28 mM | 10 nM | A cell scraper (physical harvesting) | 2, 4, and 8 weeks | – Micro-CT – Histological (H & E) analyses – Toluidine blue staining | [14] |
Mandible | Not given | 3-month-old female, domestic pigs | Triple-layer BM-MSC sheets | 48 h | – | – | Reducing the room temperature for 1 h | 6 weeks | – CT – Mineral apposition analysis – Histomorphometric analysis | [85] |
Maxillary | Not given | 4-week-old females Sprague Dawley rats | Fluorescent-labeled BM-MSC sheets | 7 days | 82 µg/mL | – | Reducing the room temperature | 2 weeks | – Micro-CT – Histological analysis – Immunohistochemical analysis | [86] |
Maxillary sinuses | Not given | Female New Zealand rabbits | Differentiated and undifferentiated BM-MSC sheets, with nasal mucosa-derived cell sheets | 2 days | – | – | Reducing the temperature below 20 °C for 30 min | 4 weeks | – H & E staining – Immunohistochemical staining – SEM – TEM | [87] |