Table 1.
Summary of experimental design and results contained in articles for regenerative effects on facial nerve injuries according to the stem cells.
| Potential Substances |
Reference | Animal Model | Surgical Procedures | Experimental Design/Therapeutic Molecules | Evaluations | Results | Conclusions |
|---|---|---|---|---|---|---|---|
| OSC | Bense et al. (2020) [33] | Fisher rats (n = 60) | Rt facial nerve transection (2 mm defect) + femoral vein conduit | Group 1: transection + faciofacial nerve suture only (n = 20) Group 2: femoral vein conduit without OSCs (n = 20) Group 3: femoral vein conduit with OSCs (n = 20) |
Facial motor performance: analysis of the interpalpebral distance during the blink reflex Synkinesis: double retrograde labeling of regenerating motoneurons |
Maximum amplitude of vibrissae protraction and retraction cycles/angular velocity were increased in Group 3. - OSC transplantation reduced synkinesis. |
OSC adjuvant to facial nerve repair surgery improves the functional recovery of facial movement and reduces synkinesis. |
| DPC | Saez et al. (2019) [48] | Wistar rats (n = 40) | Lt facial nerve compression injury + application of human iDPCs | Group 1: left nerve crushed (n = 20) Group 2: left nerve crushed + iDPCs (n = 20) Group 3: right control for left crushed nerve groups (n = 20) |
- Functional recovery: observation of whisker movement - Transmission electron microscopy: nerve morphology - Immunoblotting: NGF expression |
- Functional recovery was complete at 14 days in Group 2 but was delayed to 42 days in Group 1. - Group 2 exhibited histological improvement in axons and myelin sheaths. - Group 2 exhibited statistically greater NGF expression. |
Human iDPCs promoted regeneration of the facial nerve trunk after 14 days. |
| SHED | Pereira et al. (2019) [21] | Wistar rats (n = 17) | The buccal branch of the Lt facial nerve transection (5 mm defect) + autograft | Group 1: PGA-collagen nerve conduit with autograft (n = 7) Group 2: PGA-collagen nerve conduit with SHED (autograft, n = 10) |
CMAP amplitude: presurgery and 3 and 6 weeks after surgery -Histopathological evaluation: mean axonal density and diameter -Immunofluorescence assays |
- Mean CMAP amplitude was higher in Group 2 than in Group 1 (p < 0.001). - Mean axonal diameter and axonal density were higher in Group 2 than in Group 1 (p = 0.004). - Positive labeling for S100 Schwann-cell marker suggests initiation of differentiation in vivo. |
Regeneration was superior in the group treated with SHED |
| OSC | Esaki et al. (2019) [32] | ICR mice (n = 40) | Rt facial nerve compression injury + OSCs + Megel | Group 1: OSCs + MedGel (n = 10) Group 2: OSCs only (n = 10) Group 3: MedGel (n = 10) Group 4: Mock (DMEM/F-12 alone; n = 10) |
-Evaluation of facial nerve paralysis: eye blink, and whisker movement -CMAP amplitude: presurgery and 2 weeks after surgery -Histopathologic evaluation: 1 and 2 weeks after surgery -RT-PCR: neural stem cell markers |
- Recovery was more extensive and faster in Group 1. - Nerve function and the number of regenerated nerve fibers were increased in Group 1 |
OSC-impregnated biodegradable hydrogels produced the most prominent effect on facial nerve recovery. |
| GMSC | Zhang et al. (2018) [50] | Sprague-Dawley rats (n = 12) | The buccal branch of the Lt facial nerve transection (5 mm defect) + 3D bio-printed nerve constructs. | Group 1: silicon tube control (n = 4) Group 2: autograft (n = 4) Group 3: 3D bio-printed grafts containing human GMSCs (n = 4) |
-Facial functional analysis: 12 weeks after surgery-CMAP amplitude -Histological evaluation -Immunohistochemical studies |
- Facial palsy score was highest in Group 2 and was higher in Group 3 than in Group 1. - CAMP recovery at 12 weeks and organized axonal alignment were similar in Groups 1 and 2. |
3D bio-printed scaffold-free nerve constructs containing GMSC spheroids showed promising beneficial effects on the regeneration of damaged rat facial nerves. |
| NCSC | Zhang et al. (2018) [51] | Sprague-Dawley rats | The facial nerve transection (6 mm defect) + nerve conduit. | Group 1: controls Group 2: parental GMSCs Group 3: NCSCs |
-Facial functional analysis/CMAP amplitude-Electron microscopy: mean axonal density and diameter, myelin thickness -Histological evaluation Immunohistochemical studies |
-The induced NCSC population showed increased expression of NCSC-related genes. - NCSCs (Group 3) displayed robust differentiation into neuronal and Schwann-like cells. |
Implantation of NCSC-laden nerve conduits promoted functional regeneration of the injured nerve. |
| DFAT | Matsumine et al. (2014) [43] | Sprague-Dawley rats(n = 25) | The buccal branch of the Lt facial nerve transection (7 mm defect) + silicone tube | Group 1: silicone tube containing type I collagen gel only (n = 7) Group 2: silicone tube containing DFAT (n = 9) Group 3: autologous graft (n = 9) |
-CMAP amplitude/latency: 13 weeks after transplantation -Transmission electron microscopy -Immunofluorescence staining |
- Axon diameter and myelin thickness were increased and CMAP amplitude was significantly larger in Group 2. -No significant difference between Groups 2 and 3. |
DFAT promoted vigorous nerve regeneration. |
| ADSC | Watanabe et al. (2017) [38] | Lewis rats (n = 77) | The buccal branch of the Lt facial nerve transection (7 mm defect) + silicone tube | Group 1: silicone tube containing uADSCs (n = 16) Group 2: silicone tube containing dADSCs (n = 16) Group 3: silicone tube containing Schwann cells (n = 16) Group 4: silicone tube containing collagen gel alone (n = 16) Group 5: autologous graft (n = 13) |
-Facial functional analysis: 13 weeks after transplantation -Transmission electron microscopy -Immunofluorescence staining |
- Facial palsy scores were significantly higher in Groups 1, 2, 3, and 5 than in the control group after 6-weeks (p < 0.05) and 13-weeks (p < 0.001). - Morphometric analyses showed improved regeneration of the nerve in Groups 1–3. |
uADSCs and dADSCs may both have therapeutic potential in facial nerve regeneration as a source of Schwann cells in cell-based therapy. |
| DPC | Sasaki et al. (2014) [45] | Lewis rats (n = 18 | The buccal branch of the Lt facial nerve transection (7 mm defect) + silicone tube | Group 1: silicone tube containing collagen gel alone (n = 6) Group 2: autologous nerve graft (n = 6) Group 3: silicone tube containing DPCs (n = 6) |
-Facial functional analysis-CMAP amplitude/duration: 13 weeks after transplantation | - Scores in Group 3 were significantly lower than those in the autograft group between 3 and 10 weeks after surgery but were not significantly different at 11 weeks. - CMAP amplitude and duration in Group 3 were not significantly different from those in Group 1 or 2. |
Tubulation with DPCs promoted recovery of facial nerve defects and achieved complete recovery comparable to that of nerve autografting in rats. |
| BMSC | Salomone et al. (2013) [44] | Wistar rats (n = 48) | The mandibular branch of the Rt facial nerve transection (3 mm defect) + silicone tube | Group 1: silicone tube only (n = 12) Group 2: silicone tube containing 200 μL of Matrigel (n = 12) Group 3: silicone tube containing uBMSCs (n = 12) Group 4: silicone tube containing Schwann-like–differentiated cells or dBMSCs (n = 12) |
- CMAP amplitude, latency, duration:3 and 6 weeks after surgery - Immunohistochemical staining |
- CMAP amplitudes were highest in Groups 3 and 4. - CMAP duration was shorter and distal axonal numbers and density were increased in Group 3. | uBMSC treatment improved facial nerve regeneration. |
| MSC | Satar et al. (2012) [41] | Sprague-Dawley rats(n = 7) | The buccal branch of both facial nerve transection and anastomosis | Group 1: right anastomosed + MSCs (n = 7) Group 2: left anastomosed-only (n = 7) |
RT-PCR Apoptosis assessment |
- MSC application increased CNTF, PDGF- α, LIF, TGF- β1, BDNF and NT-3 expression (p < 0.05). | MSCs might exert differential effects on tissue-related proteins and trophic/growth factors. |
| DPC | Sasaki et al. (2011) [37] | Lewis rats (n = 10) | The mandibular branch of both facial nerve transection (7 mm defect) + silicone tube | Group 1: left PLGA tube containing DPCs (n = 10) Group 2: right PLGA tube without DPCs (n = 10) |
Immunofluorescence staining Transmission electron microscopy Osmium–toluidine blue-staining |
- Nerve repair was more rapid in Group 1 than in Group 2. - Tuj1-positive axons were present in regenerated nerves 2 months after transplantation and no mineralization was detected after 9 weeks. |
A PLGA tube filled with DPCs promoted nerve regeneration. |
CMAP: Compound muscle action potential; OSC: olfactory stem cell; iDPC: immature dental pulp stem cell; NGF: neural growth factor; SHED: stem cells from human exfoliated deciduous teeth; PGA: polyglycolic acid; ADSC: adipose-derived stem cell; GMSC: gingiva-derived mesenchymal stem cell; NCSC: neural crest stem-like cell; DFAT: dedifferentiated fat cells; uADSC: undifferentiated adipose-derived stem cell; dADSC: differentiated adipose-derived stem cell; uBMSC: undifferentiated BMSClacZ + cell; dBMSC: differentiated BMSClacZ + cell; MSC: mesenchymal stem cell; CNTF: ciliary neurotrophic factor; LIF: leukemia inhibitory factor; TGF-β1: transforming growth factor-β1; BDNF: brain-derived neurotrophic factor; NT-3: neurotrophin-3; PLGA: poly-DL-lactide-co-glycolide; DPC: dental pulp stem cell; qRT-PCR: quantitative reverse transcription polymerase chain reaction.