Adipose-derived mesenchymal stem cells: neuronal differentiation potential and neuroprotective action.

Adult mesenchymal stem cells derived from adipose tissue (ASC) offer significant practical advantages over other types of stem cells (SC) for potential clinical applications, since they can be obtained from adult adipose tissue in large amounts, can be easily cultured and expanded with a very low risk for development of malignancies. We investigated in vitro the neuronal differentiation potential of human ASC with a chemical protocol and a prolonged two-step protocol, which included sphere formation and sequential culture in brain-derived neurotrophic factor (BDNF) and retinoic acid (RA). After 30 days, about 57% ASC show morphological, immunocytochemical and electrophysiological evidence of initial neuronal differentiation. In fact, ASC display elongated shape with protrusion of two or three cellular processes, selectively express nestin and neuronal molecules (including GABA-A receptor and tyroxine hydroxilase) in the absence of glial phenotypic markers. Differentiated cells show negative membrane potential (−60 mV), delayed rectifier potassium currents and TTX-sensitive sodium currents, but they are unable to generate action potential. Considering the low efficacy and the not-fully mature neuronal differentiation, we evaluated if ASC display a neuroprotective effect. Using the H2O2-stressed neuroblastoma model in vitro, we show that ASC increase cell availability (compared to fibroblasts) and protect against apoptosis. A possible mechanism involved could be the secretion of BDNF, as reported for human BM-MSC: in this regard, we indeed find high levels of BDNF in ASCcondition medium. In addition to exert neuroprotection, soluble factors secreted by ASC promote neurite outgrowth, an additional mechanism that may favor neuroregeneration. In view of these results and their immunosuppressive action (Constantin et al, 2009), ASC may be a ready source of adult MSC to treat neurodegenerative diseases.