Mesenchymal stem cell-based therapy for peripheral nerve injuries: A promise or reality?

Table 3 Combination of mesenchymal stem cells and nerve guidance conduits for the treatment of peripheral nerve injuries

Cell source	Conduits	Models	Cell numbers	Outcome	Notes	Ref.
AT-MSCs (human)	Polycaprolactone	15 mm gap in the rat sciatic nerve	1 × 106	Improvement in axonal growth and expression of factors that aid in reinnervating muscle tissue	Poloxamer hydrogel + AT-MSCs promote more axonal growth than when AT-MSCs were delivered without it	[97]
AT-MSCs (rat)	Fibrin gel	A 20 mm segment of the sciatic nerve was excised in rats and sutured back in the reverse direction	3 × 106	Enhanced remyelination, axonal regeneration, and functional recovery	The use of AT-MSCs resulted in a significant improvement compared with the autologous nerve graft group	[98]
AT-MSCs (rat)	Silicone tube	10 mm gap in the rat sciatic nerve	1 × 106	Improvement in the recovery of walking function	The combination of AT-MSCs with platelet-rich fibrin showed better results than AT-MSCs alone	[99]
AT-MSCs (canine)	Polycaprolactone + heterologous fibrin biopolymer	12 mm gap in the rat sciatic nerve	1 × 106	Improvement in functional motors and electrophysiological recovery	The improvements observed were not significantly different from those obtained with autografts	[100]
AT-MSCs (rat)	Chitosan + acellular nerve	10 mm gap in the rat sciatic nerve	Unknown	Improvement in neurological and motor function and in the quality of the myelin sheath	At 12 weeks there was no significant difference in the degree of recovery compared with the autograft group. The electrophysiological characteristics were also similar to those of the autograft	[101]
BM-MSCs (rat)	Polycaprolactone + fibrin sealant	6-7 mm gap in the rat sciatic nerve	3 × 105	Improvement in the regeneration process, modulation of SCs, and motor functional recovery	There was no significant difference in the total estimated number of regenerated fibers between the groups	[102]
BM-MSCs (rat)	Bio 3D conduits from BM-MSCs	5 mm gap in the rat sciatic nerve	3 × 105	Improvements in nerve regeneration, kinematic analysis, and morphological parameters	No neuroma formation was found 8 weeks after the surgery. The Bio 3D group exhibited a higher abundance of myelinated axons compared with both the silicone NGC group and the silicone NGC with MSCs group	[96]
UC-MSCs (human)	Longitudinally oriented collagen conduit	A 35-mm-long segment of the dog’s sciatic nerve was removed	1 × 106	Improvements in axonal regeneration and functional recovery	Nerve regeneration was inferior to the autologous nerve graft group	[103]
UC-MSCs (human)	Bio 3D conduits from UC-MSCs	5 mm gap in the rat sciatic nerve	3 × 105	Improvements in kinematic analysis, as well as in the diameters and number of myelinated axons	The Bio 3D conduit showed better results than the silicone tube and demonstrated nerve regeneration comparable with the autologous group. UC-MSCs in the Bio 3D conduit gradually diminished until week 8	[95]
WJ-MSCs (human)	Acellular nerve	10 mm gap in the rat sciatic nerve	1 × 106	Improvements in myelin and axon regeneration, nerve function, and muscle atrophy reduction	Evaluation at 8 weeks. Increased in both the proportion of myelin in the tissue and myelin thickness, resembling the results seen in the autograft group	[104]
WJ-MSCs (human)	Poly (DL-lactide-e-caprolactone) copolyester	10 mm gap in the rat sciatic nerve	2 × 106	Improvements in nerve regeneration, functional recovery, and increased expression of neurotrophic and angiogenic factors	Evaluation at 12 weeks	[105]
OM-MSCs (rat)	Chitosan	About 10 mm gap in the rat sciatic nerve	1 × 106	Improved in nerve regeneration, motor performance, sciatic indexes, and lower gait dysfunction	The treated groups did not show a significant difference in the stereological results	[106]
GMSCs (human)	Bio 3D conduits from GMSCs	A 5 mm gap in the buccal branch of the rat facial nerve	4 × 104	Improvements in nerve regeneration and functional recovery	Effects comparable to the autograft group	[94]

AT-MSCs: Adipose tissue-derived mesenchymal stem cells; BM-MSCs: Bone marrow-derived mesenchymal stem cells; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; WJ-MSCs: Wharton’s jelly-derived mesenchymal stem cells; OM-MSCs: Olfactory mucosa-derived mesenchymal stem cells; GMSCs: Gingiva-derived mesenchymal stem cells; NGC: Nerve guidance conduit; SCs: Schwann cells; 3D: Three-dimensional.