Ultrastructural Analysis of Sciatic Nerve in Mice With Peripheral Neuropathy After Transplantation of Adipose-Derived Multipotent Mesenchymal Stromal Cells

Abstract

We investigated the peripheral demyelination in transgenic mice with peripheral neuropathy and the effect of adiposederived multipotent mesenchymal stromal cells (ADSCs) transplantation on the ultrastructural features of the sciatic nerve in these mice. The B6.Cg-Tg(PMP22)C3Fbas/J transgenic mice with peripheral neuropathy were injected intramuscularly with ADSCs, which were isolated from the adipose tissue of FVB-Cg-Tg(GFPU) mice transgenic by GFP. For ultrastructural analysis, tissue fixation in animals was performed by transcardiac perfusion-fixation with 4% formaldehyde solution and 2.5% glutaraldehyde solution 16 weeks after transplantation. Electron microscopic examination of fibers of the sciatic nerve in the transgenic mice with peripheral neuropathy showed that many axons in this nerve were subjected to dys- and demyelination; the so-called onion bulb-like structures were observed. In some fibers, hypertrophy of myelin sheaths was found. In general, ultrastructural modifications in the sciatic nerve of the transgenic mice were rather similar to the pathomorphological pattern observed in patients with peripheral neuropathy. At 16 weeks after ADSC transplantation, in the sciatic nerve in mice with peripheral neuropathy thickening of the myelin sheath and increasing of the number of lamellae were observed. Thus, ADSC transplantation in mice with hereditary peripheral neuropathy has a protective effect on the ultrastructural features of the sciatic nerve and inhibits the process of axon demyelination.

Stem Cell Therapy Enhances Motor Activity of Triceps Surae Muscle in Mice with Hereditary Peripheral Neuropathy

“…Other studies have shown that implantation of SCs derived from AD-MSCs showed improved musculoskeletal function [ 36 ] as well as decreased neuronal damage [ 37 ]. Earlier in the morphological study [ 18 ] it was shown that transplantation of AD-MSCs into mice with peripheral neuropathy of the sciatic nerve causes a thickening of the myelin sheath of axons and an increase in the number of lamellae. These results are consistent with reports of enhanced sciatic nerve regeneration by restoring the myelin sheath and axons of peripheral nerves in mice with peripheral neuropathy after MSCs transplantation [ 25 ].…”

“…Recently, in the morphological study was shown that in mice with sciatic nerve neuropathy induce both thickening of the myelin sheath and increase in the number of lamellae, after AD-MSCs transplantation. In this way, in mice with hereditary peripheral neuropathy, AD-MSCs transplantation has a protective effect on the ultrastructural features of the sciatic nerve and inhibits the process of axonal demyelination [ 18 ].…”