Review Article

Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair

Table 1

Summary of current evidence assessing the effect of different stem cell types on peripheral nerve regeneration in animal models.

Stem cell source tissue Author Experimental model Mode of delivery Therapeutic cell properties Key outcome measures

AdiposeGeorgiou et al. [99] Rat sciatic transection (15 mm gap, 8 weeks) Aligned cellular collagen constructs in a collagen tube Differentiated rat ADSCs Axon regeneration, myelination.
Hsueh et al. [185]Rat sciatic transection (10 mm gap, 6 weeks) Neurospheres seeded in a chitosan-coated silicon conduitXenogeneic hADSC neurospheresAxon regeneration, myelination, inflammation, intraneural scarring, muscle fibres, and gait.
Kingham et al. [97] Rat sciatic transection (10 mm gap, 2 weeks)Cells in fibrin matrix seeded in a fibrin conduitStimulated xenogeneic hADSCs Axon regeneration, vascularisation, cell survival, and gene expression changes in DRG and spinal cord.
Scholz et al. [186] Athymic rat sciatic transection (13 mm gap, up to 4 months) Cells in culture medium seeded in a silastic conduit Xenogeneic differentiated hADSCs Axon regeneration, extensor postural thrust, sensory evaluation, and muscle weight.
Carriel et al. [187] Rat sciatic transection (10 mm gap, 12 weeks) Cells in a fibrin-agarose hydrogel seeded in a collagen conduit Autologous ADSCs Axon regeneration, myelination, electrophysiology, pinch test, and toe spread.
Mohammadi et al. [33] Rat sciatic transection (10 mm gap, up to 12 weeks) Cells in PBS seeded in a silicone conduit Allogeneic ADSCs Nerve fibres, walking track analysis, and muscle weight.
Suganuma et al. [188] Rat sciatic transection (10 mm gap, 2 weeks) Cells in type I collagen gel seeded in a silicone conduit Autologous uncultured ADSCs Axon regeneration, Schwann cell infiltration, cell survival, and gene expression in repaired tissue.
Orbay et al. [189] Rat sciatic transection (10 mm gap, up to 6 months) Cells in collagen gel seeded in a silicone conduit Autologous ADSCs differentiated into Schwann cell-like cells Nerve fibres, vascularisation, cell survival, walking track analysis electrophysiology, and muscle weight.
Liu et al. [190] Rat sciatic transection (15 mm gap, 12 weeks) Cells in culture medium seeded in an acellular nerve allograft Allogeneic undifferentiated ADSCs Footprint analysis, sciatic functional index, electrophysiology, myelination, and nerve fibre density.
Reid et al. [191] Rat sciatic transection (10 mm gap, 2 weeks) Cells in culture medium seeded in a PCL conduit Allogeneic ADSCs differentiated into Schwann cell-like cells Gene expression changes in the DRG.
Shen et al. [192]Rat sciatic transection (10 mm gap, up to 8 weeks) Cells in culture medium seeded in a GGT conduit Allogeneic undifferentiated ADSCs Electrophysiology, walking track analysis, footprint analysis, nerve fibres, and myelination.
Sun et al. [193] Rat facial transection (8 mm gap, 8 weeks) Cells in culture medium seeded in a decellularised allogeneic artery conduit Autologous ADSCs differentiated into Schwann cell-like cells Functional evaluation of vibrissae movement, electrophysiology, morphological evaluation of regenerated nerve segments, and retrograde labelling of facial motor neurons.
Wei et al. [194] Rat sciatic transection (10 mm gap, up to 24 weeks) Cells in culture medium seeded onto a chitosan/silk fibroin conduit Allogeneic undifferentiated ADSCs Walking track analysis, footprint analysis, muscle mass, axon regeneration, and myelination.
di Summa et al. [93] Rat sciatic transection (10 mm gap, 2 weeks) Cells in culture medium seeded in a fibrin conduit Allogeneic ADSCs differentiated into Schwann cell-like cells Axon regeneration, Schwann cell infiltration.
Erba et al. [94] Rat sciatic transection (10 mm gap, 2 weeks) Cells in fibrinogen seeded in a PHB conduit Allogeneic undifferentiated ADSCs Axonal regeneration, transplanted cell tracking.
Zhang et al. [195] Rat sciatic transection (10 mm gap, 3 months) Cells in culture medium seeded in a xenogeneic acellular graft Autologous ADSCs differentiated to a neuronal phenotype Axon regeneration, myelination, and electrophysiology.
Ghoreishian et al. [196] Dog facial nerve transection (7 mm gap, 12 weeks) Cells in an alginate hydrogel seeded in a GORE-TEX® conduitAutologous undifferentiated ADSCs Axon regeneration, electrophysiology.

Bone marrow Ding et al. [36] Dog sciatic transection (50 mm gap, 6 months) Cells in culture medium seeded in a chitosan/PLGA conduit Autologous undifferentiated BMSCs Electrophysiology, muscle mass, axon regeneration, myelination, and vascularisation.
Xue et al. [37] Dog sciatic transection (60 mm gap, 12 months) Cells in saline seeded in a chitosan/PLGA conduit Autologous undifferentiated BMSCs Posture and gait analysis, electrophysiology, muscle mass, myelination, and nerve fibres.
Sakar et al. [197] Rat sciatic transection (10 mm gap, up to 8 weeks) Cells in PBS seeded in a PHBHHx nerve graft Allogeneic undifferentiated BMSCs Electrophysiology, axon regeneration, myelination, walking track analysis, and vascularisation.
Hu et al. [38] Monkey median transection (50 mm gap, 1 year) Cells in culture medium seeded in a chitosan/PLGA conduit Autologous undifferentiated BMSCs Behaviour observation, electrophysiology, myelination, safety evaluation, and axon regeneration.
Wakao et al. [39] Monkey median transection (20 mm gap, 1 year) Cells in a collagen sponge seeded in a biodegradable conduit Autologous BMSCs differentiated to Schwann cell-like cells Cell proliferation for local tumour formation, electrophysiology, hand movement analysis, immunocytochemistry, general health follow-up, immune response, myelination, and axon regeneration.
Oliveira et al. [156] Mouse median transection (2 mm gap, 8 weeks) Cells in culture medium seeded in a PCL conduit Autologous undifferentiated BMSCs Myelination, nerve fibres, electrophysiology, muscle mass, creatine phosphokinase levels, grasping test, and immunohistochemistry.
Ladak et al. [34] Rat sciatic transection (12 mm gap, 12 weeks) Cells in culture medium seeded in a biodegradable collagen nerve guide Autologous BMSCs differentiated to Schwann cell-like cells Electrophysiology, axon regeneration, and muscle mass.
Mohammadi et al. [198] Rat sciatic transection (10 mm gap, up to 12 weeks) Cells in PBS seeded in an inside-out vein graft Allogeneic undifferentiated BMSCs Walking track analysis, immunohistochemistry, muscle mass, axon regeneration, and myelination.

Embryonic Cui et al. [28] Rat sciatic transection (10 mm gap, up to 3 months) Cells in culture medium seeded into the gap between the nerve stumps with the surrounding epineurium as a natural conduit Xenogeneic mouse ESCs differentiated into neural progenitor cells Electrophysiology, axon regeneration, and myelination.

Umbilical cord (Wharton’s Jelly) Matsuse et al. [102] Rat sciatic transection (8 mm gap, up to 21 days) Cells in Matrigel seeded in transpermeable tubes Allogeneic umbilical cord stem cells differentiated into Schwann cell-like cells Walking track analysis, immunohistochemistry, myelination, and axonal regeneration.

Dental pulp Matsushita et al. [199] Rat sciatic transection (3 mm gap, up to 32 weeks) Cells in PBS seeded in a chitosan conduit Xenogeneic human whole dental pulp Immunohistochemistry, myelination, and axon regeneration.

Neural tissue Ni et al. [80] Rat sciatic transection (15 mm gap, up to 12 weeks) Cells in culture medium seeded in a PLA conduit Xenogeneic mouse undifferentiated NSCs Walking track analysis, sciatic functional index, electrophysiology, revascularisation, axon regeneration, and myelination.
Liard et al. [79] Pig femoral transection (30 mm gap, up to 240 days) Neurospheres seeded in an autologous venous bridge Allogeneic undifferentiated NSCs Electromyography, thigh flexion, and phenotypic characterization of grafted cell progeny.

Skin Park et al. [73] Pig femoral transection (10 mm gap, up to 4 weeks) Cells in fibrin glue seeded in a Lyoplant® conduit Autologous undifferentiated SKPs Axon regeneration, nerve fibres.

iPSCs Uemura et al. [86] Mouse sciatic transection (5 mm gap, up to 48 weeks) Neurospheres seeded in a PCL/PLA conduit Mouse iPSCs differentiated to neurospheres Print length factor, foot withdrawal, histomorphometry, and myelination.
Wang et al. [45] Rat sciatic transection (10 mm gap, 1 month) Cells in Matrigel seeded in a PCL/PLA/sodium acetate conduit Human iPSCs differentiated to neural crest stem cells Myelination, axon regeneration, electrophysiology, and cell survival.

ADSCs: adipose derived stem cells; hADSCs: human adipose derived stem cells; DRG: dorsal root ganglion; PBS: phosphate buffered saline; PCL: poly-ε-caprolactone; GGT: genipin cross-linked gelatin annexed with tricalcium phosphate ceramic particles; PHB: poly-3-hydroxybutyrate; PLGA: poly(lactic-co -glycolic acid); BMSCs: bone marrow stem cells; PHBHHx: poly(3-hydroxybutyrate-co-3- hydroxyhexanoate); ESCs: embryonic stem cells; PLA: polylactic acid; NSCs: neural stem cells; SKPs: skin derived precursors; iPSCs: induced pluripotent stem cells.