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

Table 4 Transplantation of Schwann-like cell-derived mesenchymal stem cells in peripheral nerve injuries

Starting cell	Delivery	Models	Method of transdifferentiation	Cell numbers	Effects	Notes	Ref.
AT-MSCs (rat)	Nerve fibrin conduit	10 mm gap in the rat sciatic nerve	Chemical and growth factors	2 × 106	Improvement in axonal regeneration	No undifferentiated MSC transplantation group. Similar outcomes were observed between the SLCs derived from AT-MSCs and BM-MSCs 2 weeks post-transplantation	[125]
AT-MSCs (rat)	Nerve fibrin conduit	10 mm gap in the rat sciatic nerve	Chemical and growth factors	2 × 106	Improvement in axonal and fiber diameters and reduction in muscle atrophy (gastrocnemius)	No undifferentiated MSC transplantation group. SLCs derived from AT-MSCs were more effective than those derived from BM-MSCs after 4 months	[126]
AT-MSCs (rat)	Silicone tube	10 mm gap in the rat sciatic nerve	Chemical and growth factors	1 × 106	Improvement in axonal regeneration, sciatic function index, and myelination	AT-MSCs and SLCs exhibited a similar impact on nerve regeneration 6 months post-transplantation	[127]
AT-MSCs (human)	Local injection	Tibial crush in rats	Chemical and growth factors	1 × 105	Improvement of survival and myelin formation rates	AT-MSCs secreted neurotrophic factors, though in lower quantities compared with SLCs, and expressed glial markers p75 and GFAP even without stimulation	[128]
AT-MSCs (rat)	NeuraWrapTM sheath	15 mm gap in the rat sciatic nerve	Chemical and growth factors	4 × 106	Improvement in axonal regeneration and myelination. The conduits containing SLCs resulted in a 3.5-fold greater proportion of axons in the distal nerve stump compared with the empty conduits after 8 weeks	No undifferentiated MSC transplantation group	[129]
AT-MSCs (rat)	Silicone tube	7 mm gap in the rat facial nerve	Chemical and growth factors	1 × 105	Improvement in axonal regeneration and in the functional recovery of the facial nerve	AT-MSCs, SLCs, and SCs showed similar nerve regeneration potential after 13 weeks	[130]
AT-MSCs (ovine)	Acellular nerve allograft	30 mm gap in the ovine peroneal nerve	Chemical and growth factors	3 × 105	Improvement in hindlimb function, motor recovery, and remyelination	The autograft showed better organization of the myelin sheaths and axons than acellular nerve allografts recellularized with SLCs after 12 months	[131]
AT-MSCs (ovine)	Acellular xenografts (human)	20 mm gap in the ovine sciatic nerve	Chemical and growth factors	3 × 105	Improvement in metatarsus mobility and strength. Presence of several intrafascicular axons at the graft extremes	No difference was observed between the allograft and xenograft recellularized with SLCs groups in the biceps femoris and gastrocnemius electromyographic response after 6 months	[132]
BM-MSCs (rat)	Hollow fiber	12 mm gap in the rat sciatic nerve	Chemical and growth factors	1-2 × 107	Motor nerve conduction velocity and sciatic nerve function improved significantly. There was an increase in the number of regenerated axons	No tumor formation was observed in the graft or the sciatic nerve segment after 6 months	[133]
BM-MSCs (human)	Transpermeable tube	10 mm gap in the rat sciatic nerve	Chemical and growth factors	1-2 × 107	Increase in the number of regenerated axons and improvement in the sciatic function index	Intraperitoneal administration of FK506 as an immunosuppressant during the 3 weeks of evaluation	[134]
BM-MSCs (rat)	Chitosan conduit	12 mm gap in the rat sciatic nerve	Induction of neurospheres, exposure to growth factors, and co-culture	1.5 × 105	Enhanced axonal repair and remyelination	The nerve repair and functional recovery were similar to those from sciatic nerve-derived SCs	[135]
BM-MSCs (rabbit)	Autogenous vein	10 mm gap in the rabbit facial nerve buccal branch	Chemical and growth factors	2 × 105	Improvement in axon regeneration and remyelination	SLC group provided a faster rate of axonal extension and a larger area of myelination than the BM-MSCs group	[136]
BM-MSCs (human)	Chitosan conduit	12 mm gap in the rat sciatic nerve	Induction of neurospheres, exposure to growth factors, and co-culture	1.5 × 105	Enhanced axonal regeneration and myelination	Subcutaneous administration of cyclosporin A for immunosuppression	[137]
WJ-MSCs (human)	Transpermeable tube	8 mm gap in the rat sciatic nerve	Chemical and growth factors	1-2 × 107	Improvement in axonal regeneration and functional recovery	No tumor formation was observed after 3 weeks. The ability of SLCs to promote axonal regeneration was similar to that of human SCs, as evidenced by functional recovery and histological evaluation. Subcutaneous administration of FK506 for immunosuppression	[138]
UCB-MSCs (human)	3D-cell spheroids	Sciatic nerve crush in rats	Chemical and growth factors	5 × 105	Improvement in functional and structural recovery	Subcutaneous administration of cyclosporin A for immunosuppression	[139]
GMSCs (human)	3D-collagen hydrogel	Sciatic nerve crush in rats	Encapsulation in the methacrylated 3D-collagen hydrogel	2 × 106	Improvement in axonal regeneration and functional recovery	SLCs demonstrated immunomodulatory activity, reducing M1 macrophage activation and promoting M2 macrophage polarization	[120]

AT-MSCs: Adipose tissue-derived mesenchymal stem cells; BM-MSCs: Bone marrow-derived mesenchymal stem cells; GFAP: Glial fibrillary acidic protein; GMSCs: Gingiva-derived mesenchymal stem cells; MSC: Mesenchymal stem cell; SCs: Schwann cells; SLCs: Schwann-like cells; UCB-MSCs: Umbilical cord blood-derived mesenchymal stem cells; WJ-MSCs: Wharton’s jelly-derived mesenchymal stem cells; 3D: Three-dimensional.