Facilitated Neural Differentiation of Adipose Tissue–Derived Stem Cells by Electrical Stimulation and Nurr-1 Gene Transduction

Abstract

Neuron-like cells derived from adipose tissue-derived stem cells (ADSCs) have been considered one of the most promising cells for the treatment of neurodegenerative diseases and neurotrauma in the central nervous system (CNS). Thus far, extensive efforts have been made to facilitate neuronal differentiation of ADSCs, but limited progress has been achieved. In the present study, we tested the possibility of using a combination of electrical stimulation (ES) with Nurr-1 gene transduction to promote neuronal differentiation of ADSCs. The tolerance of ADSCs to ES was first examined by a cell apoptosis assay. The proliferation of cells was characterized using a CCK-8 assay. The morphology of cells was examined by scanning electron microscopy (SEM). The differentiation of ADSCs into neuron-like cells was examined by immunocytochemistry (ICC)-immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and enzyme linked immunosorbent assay (ELISA). The gene expression of microtubule-associated protein 2 (MAP-2), b-tubulin, neurofilament 200 (NF-200), octamer binding transcription factor 4 (OCT-4), and glial fibrillary acidic protein (GFAP) after stimulation was examined by qRT-PCR. We found that the optimal intensity of ES for neuronal differentiation of ADSCs was 1 V/cm. In addition, ES combined with Nurr-1 gene transduction increased the neuronal differentiation rate of ADSCs, the length of neurite-like processes, and the secretion of dopamine. Further studies showed that a combination of ES with Nurr-1 gene transduction was capable of promoting the expression of MAP-2, b-tubulin, and NF-200 but decreased the expression of OCT-4 and GFAP. All of these findings indicate that a combination of ES with Nurr-1 gene transduction could facilitate neuronal differentiation of ADSCs, which raises the possibility of its application in the treatment of neurodegenerative diseases and neurotrauma in the CNS.

Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

“…Adipose tissue-derived stromal cells (ADSCs) are regarded as advantageous seed cells in tissue engineering [ 1 ] owing to their self-renewal capacity, multipotency, and the relative ease of obtaining them in large numbers from adipose tissue by liposuction [ 2 , 3 ]. Many studies have demonstrated the capacity of ADSCs to differentiate into neural progenitor cells or neurons [ 4 – 8 ].…”

Using Electrical Stimulation to Enhance the Efficacy of Cell Transplantation Therapies for Neurodegenerative Retinal Diseases: Concepts, Challenges, and Future Perspectives

“…In fact, ES has been shown to promote neurite outgrowth during normal developmental differentiation 160–165 as well as guide the growth direction of regenerating nerve fibers 166–168 . ES also appears to be capable of inducing the differentiation of ESCs 169 , BM-MSCs 138 , and ADSCs 170 into neurons in culture with or without simultaneous gene therapy. Thus, the dual application of stem cell therapy and a controllable electrical current may provide a novel mechanism to realize the full advantages of CT therapies for retinal repair.…”