Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats

• Published in: Neuroscience letters Vol. 597; pp. 84 - 89
• Main Authors: Xia, Nan, Xu, Jin-Mei, Zhao, Nan, Zhao, Qing-Song, Li, Ming, Cheng, Zhi-Feng
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 15.06.2015
• Subjects: Animals; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Experimental - therapy; Diabetic foot; Diabetic Foot - pathology; Diabetic Foot - physiopathology; Diabetic Foot - therapy; Electroneurogram; Femoral Nerve - metabolism; Femoral Nerve - pathology; Femoral Nerve - physiopathology; Human mesenchymal stem cells from umbilical cord matrix; Humans; Male; Mesenchymal Stem Cell Transplantation; Muscle, Skeletal - blood supply; Muscle, Skeletal - innervation; Neovascularization, Physiologic; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Nerve Degeneration - therapy; Nerve Growth Factor - blood; Neural Conduction; Neurofilament; Neurofilament Proteins - metabolism; Neurons - metabolism; NGF; Peripheral neuropathy; Rats, Sprague-Dawley; Neurofilament; Human mesenchymal stem cells from umbilical cord matrix; Peripheral neuropathy; NGF; Electroneurogram; Diabetic foot
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2015.04.038

•hMSCs-UC partially reverse the degeneration of FN via upregulation of NGF, NF-200 and angiogenesis.•hMSCs-UC reverse at least partially the damages in myelination of FN revealed by EM data.•The function of FN is improved after by hMSCs-UC revealed by compound action potential recording.•This finding supports hMSCs-UC as a potential strategy for treatment of diabetic neuropathy. Neuropathy is observed in 50% of diabetic patients with diabetic foot. This study attempted to explore the potential role of human mesenchymal stem cells-umbilical cord blood (hMSCs-UC) in femoral nerve (FN) neuropathy. The model rats were established by one time administration of streptozotocin and empyrosis on the dorsal hind foot. At 3d, 7d, 14d after treatment with hMSCs-UC or saline through left femoral artery, the serum NGF was examined by ELISA; NF-200 expression in FN was evaluated by immunohistochemistry; the diameter and roundness of FN, the ratio of capillary and muscular fiber of gastrocnemius were calculated under light microscope; and neuronal degenerations, such as demyelization, axonal atrophy, and loose arrangement of nerve fibers, were observed by electronic microscope. The results showed that, in hMSCs-UC-treated model rats, serum NGF was increased with higher positive rate of NF-200. Although the difference in FN diameters was not established among groups, improvement of roundness of FN was confirmed with increase in the numbers of capillary in FN-innervated gastrocnemius; additionally, degenerative neuropathy was significantly improved. Importantly, the functional study of electroneurogram (ENG) showed that, slowed conduction of FN in model rats was significantly restored by hMSCs-CU treatment. These data suggested that hMSCs-UC-treatment partially reverse the neuronal degeneration and nerve function of FN, which might be contributed by the upregulation of NGF with dramatic angiogenesis in FN-innervated gastrocnemius, consequently reversing neuronal structure and function, preventing or curing foot ulceration.