The effects of adipose-derived multipotent mesenchymal stromal cells transplantation on motor activity and function of the sciatic nerve in mice with peripheral neuropathy

Abstract

The Charcot–Marie–Tooth disease type 1A (SHMT1A) is one of the most common hereditary motor-sensory peripheral neuropathies, which is caused by demyelination of motor and sensory nerve fibers and leads to nerve dysfunction. There are currently no effective treatments for hereditary neuropathies, but recent studies indicate a number of potentially effective therapeutic agents, including multipotent mesenchymal stromal cells (MMSCs). The aim of the study was to evaluate the effect of adipose-derived MMSCc transplantation on motor activity and sciatic nerve function of transgenic mice with peripheral neuropathy. Materials and methods. The transgenic B6.Cg-Tg(PMP22)C3Fbas/J mice with peripheral neuropathy were injected intramuscularly with MMSCs, which were isolated from the adipose tissue of FVB-Cg-Tg(GFPU) mice transgenic by GFP. Motor activity of experimental animals was investigated in dynamics after 2, 4, 6, 8 and 10 weeks using the behavioral balance beam test. The functions of the sciatic nerve were analyzed according to the footprint test by calculating the sciatic functional index (SFI). Results. For 2-10 weeks in animals with neuropathy, disease progression was observed, which was expressed in an increasing increase in the number of slidings of the hind limbs from the beam and the time required to walking the distance. SFI in animals of this group decreased and at the 10th week was -47.0 ± 2 units. In contrast, from the 2nd week of the experiment, mice with neuropathy after MMSCs transplantation performed 20 % fewer slidings and spent 11 % less time in the balance beam test compared to animals without cell transplantation. In the same period, an increase of SFI up to -30.2 ± 2 versus -34.6 ± 0.9 units was observed, respectively. At the 10th week after the injection of MMSC, the SFI value was -10.1 ± 2.3 units and correlated with a decrease in the number of slidings and the time spent on the balance beam test. Conclusions. MMSCs transplantation improves the sciatic functional index and fine motor skills in mice with peripheral neuropathy. MMSCs have the potential to be an effective therapeutic agent in the treatment of peripheral neuropathy at Charcot-Marie-Tooth disease.

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

“…Murine AD-MSCs cultures were obtained and characterized as described previously [ 9 ]. The FVB-C-Tg(GFPU)5Nagy/J mice were euthanized by cervical dislocation under the anesthesia with 2.5% solution of 2,2,2-tribromethanol (avertin at a dose 400 mg/kg).…”

“…For the purpose of research and diagnosis of CMT1A disease, neurophysiological methods are often used to determine the speed of conduction in a nerve or muscle [ 6 , 8 ], as well as various behavioral tests [ 7 , 9 ]. In addition, some researchers use gene therapy to treat CMT1A.…”

Differentiation of neurosphere after transplantation into the damaged spinal cord

“…Motor deficits and disability often accompany spinal trauma involving annotation methods or prosthetics. The field of medicine related to neuron transplantation of stem cells (SC), analysis of their survival and behavior after transplantation, and the study of the influence of SC on compensatory processes in experimental models of brain damage in laboratory animals are rapidly developing [1][2][3][4][5].…”