Although intravenous administration of mesenchymal stem cells (MSCs) is effective for experimental stroke, low engraftment and the limited functional capacity of transplanted cells are critical hurdles for clinical applications. C–C motif chemokine ligand 2 (CCL2) is associated with neurological repair after stroke and delivery of various cells into the brain via CCL2/CCR2 (CCL2 receptor) interaction. In this study, after CCL2-overexpressing human umbilical cord-derived MSCs (hUC-MSCs) were intravenously transplanted with mannitol in rats with middle cerebral arterial occlusion, we compared the differences between four different treatment groups: mannitol + CCL2-overexpressing hUC-MSCs (CCL2-MSC), mannitol + naïve hUC-MSCs (M-MSC), mannitol only, and control. At four-weeks post-transplantation, the CCL2-MSC group showed significantly better functional recovery and smaller stroke volume relative to the other groups. Additionally, we observed upregulated levels of CCR2 in acute ischemic brain and the increase of migrated stem cells into these areas in the CCL2-MSC group relative to the M-MSC. Moreover, the CCL2-MSC group displayed increased angiogenesis and endogenous neurogenesis, decreased neuro-inflammation but with increased healing-process inflammatory cells relative to other groups. These findings indicated that CCL2-overexpressing hUC-MSCs showed better functional recovery relative to naïve hUC-MSCs according to the increased migration of these cells into brain areas of higher CCR2 expression, thereby promoting subsequent endogenous brain repair.

PurposeWe previously reported that insulin resistance, low high-density lipoprotein (HDL) cholesterol, and glycaemic exposure Index are independently associated with peripheral neuropathy in Korean patients with type 2 diabetes mellitus. We followed the patients who participated in that study in 2006 for another 6 years to determine the relationship between insulin resistance and neuropathy.Materials and MethodsThis study involved 48 of the original 86 Korean patients with type 2 diabetes mellitus who were referred to the Neurology clinic for the assessment of diabetic neuropathy from January 2006 to December 2006. These 48 patients received management for glycaemic control and prevention of diabetic complications in the outpatient clinic up to 2012. We reviewed blood test results and the nerve conduction study findings of these patients, taken over a 6-year period.ResultsLow HDL cholesterol and high triglycerides significantly influenced the development of diabetic neuropathy. Kitt value (1/insulin resistance) in the previous study affected the occurrence of neuropathy, despite adequate glycaemic control with HbA1c <7%. Insulin resistance affected the development of diabetic neuropathy after 6 years: insulin resistance in 2006 showed a positive correlation with a change in sural sensory nerve action potential in 2012.ConclusionDiabetic neuropathy can be affected by previous insulin resistance despite regular glycaemic control. Dyslipidaemia should be controlled in patients who show high insulin resistance because HDL cholesterol and triglycerides are strongly correlated with later development of diabetic neuropathy.

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In addition to chronic hyperglycemia, insulin resistance itself has been proposed to cause a diabetic neuropathy. We evaluated the role of insulin resistance in the pathogenesis of peripheral and autonomic neuropathy in patients with type 2 diabetes. Eighty-six patients with type 2 diabetes were evaluated for the anthropometric and biochemical profiles, and Kitt value was calculated from insulin tolerance test to assess the insulin resistance. Various autonomic function tests, nerve conduction velocity, and quantitative sensory tests were performed to assess autonomic and peripheral neuropathy. In univariate analysis, both autonomic and peripheral neuropathy were significantly associated with glycemic exposure index (GE index), HDL-cholesterol, duration of DM, and Kitt value. In stepwise linear regression analysis, GE index was an independent predictor of autonomic and peripheral neuropathy (β = 0.643, P < 0.001; β = 0.207, P = 0.013, respectively), and Kitt value was also an independent factor for the autonomic and peripheral neuropathy (β = - 0.306, P < 0.001; β = - 0.329, P < 0.001, respectively). Low HDL-cholesterol increased the odds ratio for peripheral neuropathy. Insulin resistance is independently associated with peripheral and autonomic neuropathy in Korean Type 2 diabetic patients along with hyperglycemia and HDL-cholesterol.