Table 2.
Cell-based therapies for PNR.
| Cell type | Defect size, location, animal model | Outcomes | References |
|---|---|---|---|
| Schwann cells | 15 mm, sciatic nerve, rat | Schwann cells overexpressing FGF-2 in a chitosan conduit supported the early regenerative process; | Meyer et al., 2016a |
| 5 mm, bilateral cavernous nerves, rat | Simple Schwann cells or GDNF-transduced Schwann cells grafts led to 75 % and 94 % success rate, respectively, compared to the 25 % of autografts; | May et al., 2016 | |
| In vitro, micro-patterned surface fabricated by laser ablation with NGF | When co-culturing with Schwann cells, NSCs differentiated into neuronal cells with robust expression of βIII tubulin and microtubule-associated protein-2; | Yeh et al., 2017 | |
| 5 mm, laryngeal nerve, rat | Laminin-chitosan-PLGA NGC combined with Schwann and NSC promoted significantly higher nerve regeneration when compared to acellular grafts; | Li Y. et al., 2018 | |
| In vitro co-culture of Schwann cells and DRGs | Schwann cells in co-culture with DRGs promoted longer neurite extension and formation of myelin around DRG neurites; | Wu et al., 2018 | |
| Bone Marrow stem cells (BMSCs) | 20 mm autograft, sciatic nerve, rat | BMSCs can differentiate into Schwann cell-like phenotype and myelinate axons, also expressing neuronal markers such as GFAP and S100; | Keilhoff and Fansa, 2011 |
| 10 mm, sciatic nerve, rat | Tropomyosin receptor kinase A overexpression enhanced the efficacy of BMSCs on PNR and improved functional recover; | Zheng et al., 2017 | |
| Contusion injury of the spinal cord, rat | Intravenous delivered BMSCs exosomes tend to migrate into the injury site, where they exert their beneficial effects; | Lankford et al., 2018 | |
| Undifferentiated adipose derived stem cells (ADSCs) | 10 mm, sciatic nerve, rat | Number and diameter of the myelinated fibers were significantly higher in the case of silicone NGC loaded with ADSCs; | Santiago et al., 2009 |
| 6 mm, sciatic nerve, rat | Decreased muscular atrophy and enhanced PNR when PCL conduits were loaded with ADSCs; | Mohammadi et al., 2013b | |
| Blunted injury, sciatic nerve, mouse | Transplanted ADSCs did not differentiate into Schwann cells but promoted PNR, since they encouraged axon regeneration, formation of myelin and restoration of denervated muscle atrophy; | Sowa et al., 2016 | |
| 15 mm, sciatic nerve, rat | ADSCS injected directly in the muscles connected to the damaged nerve were found to have increased presence of IL−10 and Ki67, which helped in delaying the onset of muscular atrophy; | Schilling et al., 2019 | |
| Differentiated adipose derived stem cells (ADSCs) | 10 mm, sciatic nerve, rat | Schwann cell-like differentiated ADSCs were found to express neurotrophic factors, namely NGF, BDNF, glial-GDNF, and NT4. The same study also reported an increase of anti-apoptotic m-RNA of Bcl-2 as well as a decrease of pro-apoptotic m-RNA Bax and caspase-3, which lead to a neuroprotective state; | Reid et al., 2011 |
| Human umbilical-cord stem cells (HUCMSCs) | 10 mm, sciatic nerve, rat | HUCMSCs increased the expression of neurotrophic and angiogenic factors, which led to a more favorable environment for nerve regeneration; | Shalaby et al., 2017 |
| 10 mm, sciatic nerve, rat | Wharton jelly-derived stem cells, in addition to an injection of dexamethasone resulted in advanced regeneration compared to the autograft; | Moattari et al., 2018 | |
| Olfactory ensheathing cells (OECs) | 8 mm, sciatic nerve, rat | PLLA NGC seeded with OEC encouraged nerve regeneration similarly to the autograft group; | Kabiri et al., 2015 |
| In vitro, to test how OECs promote neurite outgrowth of cortical neurons in an inhibitory scar-like culture model | It was found that OECs enhanced neurite elongation through direct contact and alignment of neuronal and OEC processes in scar-like cultures; | Khankan et al., 2015 | |
| 5 mm, facial nerve, rat | OECs transplanted within the NGC improved regeneration of transected facial nerve, with large numbers of myelinated nerve fibers, crude fibers, larger myelin thickness and volume in the transplanted graft; | Gu et al., 2019 | |
| Neural stem cells (NSCs) | Intra-orbital crush, optic nerve, mouse | Intravitreally grafted NSCs differentiated into astrocytes that survived in the host eyes, stably expressed CNTF and significantly attenuated the loss of the axotomized retinal ganglion. The CNTF-secreting NSCs also induced long-distance regrowth of the lesioned retinal ganglion axons; | Flachsbarth et al., 2014 |
| 3 mm, sciatic nerve, mouse | The addition of IL12p80 together with NSCs in NGCs improved motor function recovery, promoted nerve regeneration and increases the diameter of newly regenerated nerve up to 4.5 fold. | Lee et al., 2017 | |
| Skin-derived precursors (SKPs) | 10 mm, sciatic nerve, miniature pigs | SKPs transplantation showed better in vivo nerve regeneration potential than in the non-cell transplantation control group, with increasing expression of S100 and P75NGFR; | Park et al., 2012 |
| Cutaneous nerve regeneration, 1 × 1.5 cm2 circular island of skin, mouse | SKPs were found to be neurotropic toward injured nerves. They had a full capacity to differentiate into Schwann cells and promote axon regeneration. SKPs revealed to be an active participant in cutaneous nerve homeostasis; | Chen et al., 2012 | |
| 15 mm, sciatic nerve, rat | The addition of Schwann cell – like SKPs increased sciatic nerve functional index, peak amplitudes, nerve conduction velocities, number of myelinated fibers, and decreased muscle atrophy; | Wang et al., 2016 | |
| Genetically modified cells | 10 mm, sciatic nerve, rat | The transfected cells secreted GDNF at higher rate which enabled better survival of motor neurons when compared to controls. Furthermore, there was an enhanced expression of GDNF mRNA; | Li et al., 2006 |
| 15 mm, sciatic nerve, rat | FGF-2 overexpressing Schwann cells were seeded in a chitosan film inside a chitosan conduit, which enhanced nerve regeneration; | Meyer et al., 2016b | |
| End-to-end suture, sciatic nerve, rat | GDNF-expressing ADSCs revealed a robust expression of GDNF throughout time, where regeneration of nerve was significantly improved as evidenced by enhanced functional recovery, nerve reinnervation, Schwann cell migration and proliferation, axon regeneration, myelination, and angiogenesis; | Hsu et al., 2017 | |
| 10 mm, sciatic nerve, rat | KLF7-transfected Schwann cells enhanced motor and sensory axonal regeneration. Myelinated fibers were also significantly higher; | Wang Y. et al., 2017 |