Human Umbilical Cord Mesenchymal Stem Cells Overexpressing Nerve Growth Factor Ameliorate Diabetic Cystopathy in Rats

Abstract

Diabetic cystopathy is a common complication of voiding disorders in diabetes mellitus. Neuropathy and bladder remodeling underlie the lack of efficacy of pharmacological and surgical treatments. Previous studies have shown that decreased levels of nerve growth factor (NGF) are closely associated with disease progression. Besides, application of human umbilical cord mesenchymal stem cells (hUC-MSCs) is also considered a promising therapeutic strategy for treatment of diabetic neuropathy. In our study, we determine the therapeutic efficacy and mechanisms of hUC-MSCs which transfected with NGF geen in ameliorating diabetic cystopathy for the first time. We transducted hUC-MSCs with NGF-expressing lentivirus so that the hUC-MSCs can express NGF efficiently, then the NGF-expressing hUC-MSCs were intrathecally administrated in L6-S1 spinal cord of diabetic rats 3 days after induced by streptozotocin. Nine weeks later, the level of neurotrophins and voiding function of bladder were detected. Results show that improvements in voiding function were related to the neurotrophins and cytokines released by the intrathecally transplanted hUC-MSCs. In addition, the hUC-MSCs also differentiated into neurons and astrocytes within the spinal cord in rats. These two mechanisms play a combined role in neural regeneration and the amelioration of the symptoms of diabetic cystopathy.

Keywords: Diabetic cystopathy; Functional study; Human umbilical cord mesenchymal stem cells (hUC-MSCs); Intrathecal administration; Nerve growth factor (NGF).