Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2018; 10(3): 23-33
Published online Mar 26, 2018. doi: 10.4252/wjsc.v10.i3.23
Physiologically based microenvironment for in vitro neural differentiation of adipose-derived stem cells
Adriana Carol Eleonora Graziano, Rosanna Avola, Vincenzo Perciavalle, Ferdinando Nicoletti, Gianluca Cicala, Marinella Coco, Venera Cardile
Adriana Carol Eleonora Graziano, Rosanna Avola, Vincenzo Perciavalle, Marinella Coco, Venera Cardile, Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania 95123, Italy
Ferdinando Nicoletti, Department of Biomedical and Biotechnological Sciences, Section of Pathology and Oncology, University of Catania, Catania 95123, Italy
Gianluca Cicala, Department of Civil Engineering and Architecture, University of Catania, Catania 95125, Italy
Author contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data; Graziano ACE and Cardile V contributed to the study concept and design; Graziano ACE, Avola R and Coco M contributed to the acquisition of data; Graziano ACE, Avola R, Coco M and Cicala G contributed to the analysis and interpretation of data; Graziano ACE and Cardile V contributed to the drafting of the manuscript; Perciavalle V, Nicoletti F and Cardile V contributed to the critical revision of the manuscript for important intellectual content; all the authors have given final approval of the version to be published and agree to be accountable for all aspects of the work.
Supported by University of Catania, Italy, FIR, No. 21040104, UPB: 20722142002; 20130143007 (partially).
Conflict-of-interest statement: All authors declare no potential conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Adriana Carol Eleonora Graziano, PhD, PharmD, Research Fellow, Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Via Santa Sofia 97, Catania 95123, Italy.
Telephone: +39-09-54781324
Received: February 19, 2018
Peer-review started: February 19, 2018
First decision: March 13, 2018
Revised: March 20, 2018
Accepted: March 21, 2018
Article in press: March 21, 2018
Published online: March 26, 2018

The limited capacity of nervous system to promote a spontaneous regeneration and the high rate of neurodegenerative diseases appearance are keys factors that stimulate researches both for defining the molecular mechanisms of pathophysiology and for evaluating putative strategies to induce neural tissue regeneration. In this latter aspect, the application of stem cells seems to be a promising approach, even if the control of their differentiation and the maintaining of a safe state of proliferation should be troubled. Here, we focus on adipose tissue-derived stem cells and we seek out the recent advances on the promotion of their neural differentiation, performing a critical integration of the basic biology and physiology of adipose tissue-derived stem cells with the functional modifications that the biophysical, biomechanical and biochemical microenvironment induces to cell phenotype. The pre-clinical studies showed that the neural differentiation by cell stimulation with growth factors benefits from the integration with biomaterials and biophysical interaction like microgravity. All these elements have been reported as furnisher of microenvironments with desirable biological, physical and mechanical properties. A critical review of current knowledge is here proposed, underscoring that a real advance toward a stable, safe and controllable adipose stem cells clinical application will derive from a synergic multidisciplinary approach that involves material engineer, basic cell biology, cell and tissue physiology.

Keywords: Adipose stem cells, Biomaterials, Neurodegeneration, Neural differentiation, Physiological microenvironment

Core tip: Adipose-derived stem cells are easily accessible from liposuction, obtained in large quantity and cultured for several months with low levels of senescence. Moreover, they could be induced toward a neural phenotype in vitro. The preclinical studies show that microenvironment has a predominant role. Our objective is to consolidate the current literature to better delineate the functional response of adipose-derived stem cells to biochemical, biophysical or dimensional stimuli. Specifically, chemicals - like drugs and growth factors-biomaterials and microgravity are here discussed as both single and co-applied parameters for inducing a neural lineage.