The effects of adipocyte derived stem cell treatment on streptozotocin induced diabetic neuropathy

Diabetic neuropathy (DN) is the most common degenerative complication associated with diabetes mellitus. DN, a result of damage to peripheral nerves, often causes numbness, weakness, severe pain and ulcerations, usually in feet and hands. DN is one of the important health problems of today with its high morbitide ratio and increasing prevalence values. Despite widespread cognizance of DN, the only effective treatments are blood glucose control and pain management. The aim of our study was to determine the effect of adipose derived stem cell (ADSC) therapy on sciatic nerves in diabetic neuropathy using electromyographic (EMG), histochemical and immunofluorescence analyses. A total of 27 BALB/c mice were randomly divided into 3 groups: control group, DM (Diabetes + Serum physiologic treatment) group and AT-KH (Diabetes + ADSC treatment) group. In EMG, compound muscle action potential (CMAP) amplitude in the sciatic nerves was lower but distal latency were higher in the diabetes group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AT-KH group compared with the diabetes group. Distal latency in the sciatic nerve were lower in the AT-KH group compared with the diabetes group. Sciatic nerve light microscopy findings of diabetic mice showed axonal atrophy, endoneurial oedema, polimorf nuclear leukocyte (PMNL) infiltration, vacuolization and lamellar separation of axonal myelins (myelin destructions). Histologic examination of the tissues in animals treated ADSC showed remarkable improvement in microscopic morphology of myelinated and non-myelinated fibers, PMNL infiltration and demiyelinization decreased seriously. Axonal degeneration was not observed. Lamellar separation of myelins was less obvious. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted ADSC, selectively localized in the sciatic nerves. Transplantation of ADSC increased protein expression of S100, cdk2, NGF, DHH and VEGF that impaired with diabetes in sciatic nerves. VEGF levels did not demonstrate significant changes compared with the Control group. In the present study, our findings suggest that ADSC transplantation improved DN through signal-regulatory effect on schwann cell, neurotrophic actions and restoration of myelination.