Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats.
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.
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Nan
N
Xia
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Jin-Mei
JM
Xu
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Nan
N
Zhao
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Qing-Song
QS
Zhao
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: 1982795764@qq.com.
Ming
M
Li
Department of Endocrinology and Metabolism, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: chengzhifeng@ems.hrbmu.edu.cn.
Zhi-Feng
ZF
Cheng
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017719:Diabetic Foot / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005267:Femoral Nerve / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation; D018919:Neovascularization, Physiologic; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020932:Nerve Growth Factor / Q000097:blood; D009431:Neural Conduction; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D017207:Rats, Sprague-Dawley
D016900:Neurofilament Proteins; C051774:neurofilament protein H; D020932:Nerve Growth Factor
Diabetic foot; Electroneurogram; Human mesenchymal stem cells from umbilical cord matrix; NGF; Neurofilament; Peripheral neuropathy