Abstract
We examined the effect of transplantation of allogenic adipose-derived stem cells (ADSCs) with properties of mesenchymal stem cells (MSCs) on posttraumatic sciatic nerve regeneration in rats. We suggested an approach to rat sciatic nerve reconstruction using the nerve from the other leg as a graft. The comparison was that of a critical 10 mm nerve defect repaired by means of autologous nerve grafting versus an identical lesion on the contralateral side. In this experimental model, the same animal acts simultaneously as a test model, and control. Regeneration of the left nerve was enhanced by the use of ADSCs, whereas the right nerve healed under natural conditions. Thus the effects of individual differences were excluded and a result closer to clinical practice obtained. We observed significant destructive changes in the sciatic nerve tissue after surgery which resulted in the formation of combined contractures in knee and ankle joints of both limbs and neurotrophic ulcers only on the right limb. The stimulation of regeneration by ADSCs increased the survival of spinal L5 ganglia neurons by 26.4%, improved sciatic nerve vascularization by 35.68% and increased the number of myelin fibers in the distal nerve by 41.87%. Moreover, we have demonstrated that S100, PMP2, and PMP22 gene expression levels are suppressed in response to trauma as compared to intact animals. We have shown that ADSC-based therapy contributes to significant improvement in the regeneration.
Highlights
The major pathogenesis element in the case of peripheral nerve injury is the destruction of neurons
A peripheral myelin protein-22 (PMP22) which is involved in the formation of a myelin sheath is one of the key proteins involved in its post-traumatic repair
Fourteen days following the surgery -autologous nerve graft and transplantation of adipose-derived stem cells (ADSCs) expressing green fluorescent protein- the inserted cells were localized with the help of the IVIS Spectrum system
Summary
The major pathogenesis element in the case of peripheral nerve injury is the destruction of neurons. The use of microsurgical methods and modern suture material minimizes the risk of additional injury during interventions on nervous trunks; the restoration of the limb function often fails because the autologous reserves are limited To solve this problem, injured nerve regeneration is stimulated using growth and trophic factors as well as stem cells from various sources (de Luca et al, 2015) that show neuroprotective effect; another option is gene therapy (Hoyng et al, 2015). Due to the expression of such proteins, ADSCs may have an impact on different stages of structural and functional recovery of an injured nerve, from axon growth and Schwann cell proliferation to nerve fiber myelination and restoration of their conductivity (Heine et al, 2004; Carlson et al, 2011; Zack-Williams et al, 2015). Antibiotics and analgesics were administered as follows: 1 mL gentamicin (25 mg/kg, Omela, Russian Federation) was injected intramuscularly for 7 consecutive days; buprenorphine (0.5 mg/kg) was injected subcutaneously for about 7 days after surgery to minimize pain
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