Glial-Like Differentiation Potential of Human Mature Adipocytes Antonella Poloni & Giulia Maurizi & Federica Foia & Eleonora Mondini & Domenico Mattiucci & Patrizia Ambrogini & Davide Lattanzi & Stefania Mancini & Massimo Falconi & Saverio Cinti & Attilio Olivieri & Pietro Leoni Received: 23 April 2014 /Accepted: 28 May 2014 # Springer Science+Business Media New York 2014 Abstract The potential ability to differentiate dedifferentiated adipocytes into a neural lineage is attracting strong interest as an emerging method of producing model cells for the treatment of a variety of neurological diseases. Here, we describe the efficient conversion of dedifferentiated adipocytes into a neural-like cell population. These cells grew in neurosphere-like structures and expressed a high level of the early neuroectodermal marker Nestin. These neurospheres could proliferate and express stemness genes, suggesting that these cells could be committed to the neural lineage. After neural induction, NeuroD1, Sox1, Double Cortin, and Eno2 were not expressed. Patch clamp data did not reveal different electrophysiological properties, indicating the inability of the- se cells to differentiate into mature neurons. In contrast, the differentiated cells expressed a high level of CLDN11, as demonstrated using molecular method, and stained positively for the glial cell markers CLDN11 and GFAP, as demonstrated using immunocytochemistry. These data were confirmed by quantitative results for glial cell line-derived neurotrophic factor production, which showed a higher secretion level in neurospheres and the differentiated cells compared with the untreated cells. In conclusion, our data demonstrate morpho- logical, molecular, and immunocytochemical evidence of ini- tial neural differentiation of mature adipocytes, committing to a glial lineage. Keywords Dedifferentiated adipocytes . Neurosphere . Differentiation . Glial-like cells Introduction White mature adipocytes give rise to so-called dedifferentiated adipocytes that spontaneously undergo multilineage differen- tiation (Wei et al. 2013). In previous work, we demonstrated that mature adipocytes isolated from visceral and subcutane- ous adipose tissue expressed stem cell genes (Nanog, Sox17, Gata4, Tbx1, CD34, CD117, CD271, CD133, CD45, CD90), as well as reprogramming genes (Oct4, Klf4, c-myc, and Sox2) (Poloni et al. 2012). All these stemness markers studied at the molecular level were also expressed as surface antigens, and typical mesenchymal stem cell (MSC) markers were highly preserved at the molecular and antigenic levels, even after the dedifferentiation process. Thus, these data suggested the plastic properties of adipocytes. We have focused our attention on dedifferentiated adipo- cytes because they can be cultured with a similar proliferation rate as bone marrow-derived MSCs but can be obtained using a less invasive procedure. As MSCs derived from other sources, dedifferentiated adipocytes can also be induced to differentiate into non-mesenchymal lineages (Jumabay et al. 2014). A recent study showed that human dedifferentiated adipocytes expressed evidence of pluripotency with a maxi- mum at 5 – 7 days after multiple stem cell isolation The authors Antonella Poloni and Giulia Maurizi contributed equally to the work. A. Poloni (*) : G. Maurizi : F. Foia : D. Mattiucci : S. Mancini : A. Olivieri : P. Leoni Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Via Tronto, 60020 Ancona, Italy e-mail: a.poloni@univpm.it E. Mondini : S. Cinti Dipartimento di Medicina Sperimentale e Clinica, Università Politecnica delle Marche, Ancona, Italy P. Ambrogini : D. Lattanzi Dipartimento di Scienze della Terra, della Vita e dell’Ambiente, Sezione di Fisiologia, Università di Urbino Carlo Bo, Urbino, Italy M. Falconi Clinica Chirurgia del Pancreas, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy J Mol Neurosci DOI 10.1007/s12031-014-0345-0