Adipose-Derived Stem Cells for Nerve Repair: Hype or Reality?

Kingham, Paul J.; Reid, Adam J.; Wiberg, Mikael

doi:10.1159/000369336

Cited by 17 publications

(12 citation statements)

References 67 publications

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“…In spite of different germ layer origins, adipose derived stem cells have been speculated to improve regenerative outcomes after a peripheral nerve injury 3 , 4 . Early surgical nerve repair and reconstruction of injuries is favorable compared to delayed procedures 5 , 6 , stressing the need for immediately available cell sources for any therapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo

Frost

Andersson

Johansson

et al. 2018

Sci Rep

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Electrospinning can be used to mimic the architecture of an acellular nerve graft, combining microfibers for guidance, and pores for cellular infiltration. We made electrospun nerve guides, from polycaprolactone (PCL) or poly-L-lactic acid (PLLA), with aligned fibers along the insides of the channels and random fibers around them. We bridged a 10 mm rat sciatic nerve defect with the guides, and, in selected groups, added a cell transplant derived from autologous stromal vascular fraction (SVF). For control, we compared to hollow silicone tubes; or autologous nerve grafts. PCL nerve guides had a high degree of autotomy (8/43 rats), a negative indicator with respect to future usefulness, while PLLA supported axonal regeneration, but did not outperform autologous nerve grafts. Transplanted cells survived in the PLLA nerve guides, but axonal regeneration was not enhanced as compared to nerve guides alone. The inflammatory response was partially enhanced by the transplanted cells in PLLA nerve grafts; Schwann cells were poorly distributed compared to nerve guide without cells. Tailor-made electrospun nerve guides support axonal regeneration in vivo, and can act as vehicles for co-transplanted cells. Our results motivate further studies exploring novel nerve guides and the effect of stromal cell-derived factors on nerve generation.

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Section: Introductionmentioning

confidence: 99%

Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo

Frost

Andersson

Johansson

et al. 2018

Sci Rep

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“…In addition to expressing glial cell markers the stimulated ADSCs have also been shown to express specific peripheral myelin proteins and can myelinate dorsal root ganglia neurons [ 36 , 37 ]. The treated ADSCs promote nerve regeneration in vivo [ 4 , 6 , 38 ] and this is likely, in large part, due to their rich secretome of neurotrophic and angiogenic factors [ 39 ]. We showed that conditioned medium from the dADSCs significantly enhanced neurite outgrowth whereas undifferentiated stem cells had little effect and this confirms our own, and other research groups, previous reports [ 19 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer

2018

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BackgroundAdipose derived stem cells can be stimulated to produce a growth factor rich secretome which enhances axon regeneration. In this study we investigated the importance of exosomes, extracellular vesicles released by many different cell types, including stem cells and endogenous nervous system Schwann cells (SCs), on neurite outgrowth.MethodsAdipose derived stem cells were differentiated towards a Schwann cell-like phenotype (dADSCs) by in vitro stimulation with a mix of factors (basic fibroblast growth factor, platelet derived growth factor-AA, neuregulin-1 and forskolin). Using a precipitation and low-speed centrifugation protocol the extracellular vesicles were isolated from the medium of the stem cells cultures and also from primary SCs. The conditioned media or concentrated vesicles were applied to neurons in vitro and computerised image analysis was used to assess neurite outgrowth. Total RNA was purified from the extracellular vesicles and investigated using qRT-PCR.ResultsApplication of exosomes derived from SCs significantly enhanced in vitro neurite outgrowth and this was replicated by the exosomes from dADSCs. qRT-PCR demonstrated that the exosomes contained mRNAs and miRNAs known to play a role in nerve regeneration and these molecules were up-regulated by the Schwann cell differentiation protocol. Transfer of fluorescently tagged exosomal RNA to neurons was detected and destruction of the RNA by UV-irradiation significantly reduced the dADSCs exosome effects on neurite outgrowth. In contrast, this process had no significant effect on the SCs-derived exosomes.ConclusionsIn summary, this work suggests that stem cell-derived exosomes might be a useful adjunct to other novel therapeutic interventions in nerve repair.

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“…Although polylactic acid seems to be functionally inferior compared to collagen and caprolactone, the optimal material and cellular compounds for biodegradable conduits are still subject of intensive research [28,30,31,32]. Furthermore, there has been frequent reporting on the use of conduits pre-seeded with Schwann cells, or pre-seeded with stem cells differentiated into Schwann cells [33,34]. However, none of these approaches have been implemented into clinical practice for various reasons.…”

Section: Discussionmentioning

confidence: 99%

Collagen Type I Conduits for the Regeneration of Nerve Defects

Klein

Vykoukal²,

Felthaus

et al. 2016

Materials

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To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve repair using a type I collagen nerve conduit. Patients were re-examined at a minimal follow-up of 14.0 months and a mean follow-up of 19.9 months. Regeneration of nerve tissue within the conduits was assessed by nerve conduction velocity (NCV), a static two-point discrimination (S2PD) test, and as disability of arm shoulder and hand (DASH) outcome measure scoring. Quality of life measures including patients’ perceived satisfaction and residual pain were evaluated using a visual analog scale (VAS). No implant-related complications were observed. Seven out of 10 patients reported being free of pain, and the mean VAS was 1.1. The mean DASH score was 17.0. The S2PD was below 6 mm in 40%, between 6 and 10 mm in another 40% and above 10 mm in 20% of the patients. Eight out of 10 patients were satisfied with the procedure and would undergo surgery again. Early treatment correlated with lower DASH score levels. The use of type I collagen in large-diameter gaps in young patients and early treatment presented superior functional outcomes.

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Adipose-Derived Stem Cells for Nerve Repair: Hype or Reality?

Cited by 17 publications

References 67 publications

Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo

Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo

Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer

Collagen Type I Conduits for the Regeneration of Nerve Defects

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