Cell and Organ Transplantology. 2020; 8(2):121-125.
The effects of adipose-derived multipotent mesenchymal stromal cells transplantation on locomotor activity and function of the sciatic nerve in mice with peripheral neuropathy
Rubtsov V.1, Govbakh I.2, Ustymenko A.3,4, Kyryk V.3,4, Tsupykov O.3,5
- 1Educational and Scientific Centre “Institute of Biology”, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
- 2Kharkiv Medical Academy of Postgraduate Education of the Ministry of Health of Ukraine, Kharkiv, Ukraine
- 3State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
- 4Chebotarev State Institute of Gerontology of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
- 5Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
The Charcot-Marie-Tooth disease type 1A (CMT1A) 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 purpose of the study was to evaluate the effect of adipose-derived MMSCs (ADSCs) transplantation on locomotor 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. Locomotor activity of experimental animals was investigated in dynamics in 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 a growing increase in the number of hindlimb paw slips from the beam and the latency to cross the beam. SFI in animals of this group decreased and at the 10th week it was -47.0 ± 2 units.
In contrast, from the 2nd week of the experiment, mice with neuropathy after ADSCs transplantation performed 20 % fewer paw slips and spent 11 % less time in the balance beam test compared to animals without cell transplantation. In the same period, there was an increase in the SFI up to -30.2 ± 2 against -34.6 ± 0.9, respectively. On the 10th week after ADSCs injection, the SFI value was -10.1 ± 2.3 units and correlated with a decrease in the number of foot slips and the time to cross the beam.
Conclusions. ADSCs transplantation improves the sciatic functional index and fine locomotor skills in mice with peripheral neuropathy. ADSCs have the potential to be an effective therapeutic agent in the treatment of peripheral neuropathy at Charcot-Marie-Tooth disease type 1A.
Key words: adipose-derived multipotent mesenchymal stromal cells; demyelination; peripheral neuropathy; sciatic functional indexFull Text PDF (preprint)
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Rubtsov V, Govbakh I, Ustymenko A, Kyryk V, Tsupykov O. The effects of adipose-derived multipotent mesenchymal stromal cells transplantation on locomotor activity and function of the sciatic nerve in mice with peripheral neuropathy. Cell and Organ Transplantology. 2020; 8(2):121-125. doi:10.22494/cot.v8i2.111