TY - JOUR
T1 - Membrane bioreactor for investigation of neurodegeneration
AU - Morelli, Sabrina
AU - Piscioneri, Antonella
AU - Curcio, Efrem
AU - Salerno, Simona
AU - Chen, Chien Chung
AU - De Bartolo, Loredana
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/10
Y1 - 2019/10
N2 - To gain a better understanding of neurodegeneration mechanisms and for preclinical evaluation of new therapeutics more accurate models of neuronal tissue are required. Our strategy was based on the implementation of advanced engineered system, like membrane bioreactor, in which neurons were cultured in the extracapillary space of poly(l-lactic acid) (PLLA) microtube array (MTA) membranes within a dynamic device designed to recapitulate specific microenvironment of living neuronal tissue. The high membrane permeability and the optimized fluid dynamic conditions created by PLLA-MTA membrane bioreactor provide a 3D low-shear stress environment fully controlled at molecular level with enhanced diffusion of nutrients and waste removal that successfully develops neuronal-like tissue. This neuronal membrane bioreactor was employed as in vitro model of β-amyloid -induced toxicity associated to Alzheimer's disease, to test for the first time the potential neuroprotective effect of the isoflavone glycitein. Glycitein protected neurons from the events induced by β-amyloid aggregation, such as the production of ROS, the activation of apoptotic markers and ensuring the viability and maintenance of cellular metabolic activity. PLLA-MTA membrane bioreactor has great potential as investigational tool in preclinical research, contributing to expand the available in vitro devices for drug screening.
AB - To gain a better understanding of neurodegeneration mechanisms and for preclinical evaluation of new therapeutics more accurate models of neuronal tissue are required. Our strategy was based on the implementation of advanced engineered system, like membrane bioreactor, in which neurons were cultured in the extracapillary space of poly(l-lactic acid) (PLLA) microtube array (MTA) membranes within a dynamic device designed to recapitulate specific microenvironment of living neuronal tissue. The high membrane permeability and the optimized fluid dynamic conditions created by PLLA-MTA membrane bioreactor provide a 3D low-shear stress environment fully controlled at molecular level with enhanced diffusion of nutrients and waste removal that successfully develops neuronal-like tissue. This neuronal membrane bioreactor was employed as in vitro model of β-amyloid -induced toxicity associated to Alzheimer's disease, to test for the first time the potential neuroprotective effect of the isoflavone glycitein. Glycitein protected neurons from the events induced by β-amyloid aggregation, such as the production of ROS, the activation of apoptotic markers and ensuring the viability and maintenance of cellular metabolic activity. PLLA-MTA membrane bioreactor has great potential as investigational tool in preclinical research, contributing to expand the available in vitro devices for drug screening.
KW - Alzheimer's disease
KW - Glycitein
KW - Membrane bioreactor
KW - Neuronal cells
KW - Neuronal tissue engineered model
KW - Poly-L-lactic acid membranes
UR - http://www.scopus.com/inward/record.url?scp=85066508749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066508749&partnerID=8YFLogxK
U2 - 10.1016/j.msec.2019.109793
DO - 10.1016/j.msec.2019.109793
M3 - Article
C2 - 31349430
AN - SCOPUS:85066508749
SN - 0928-4931
VL - 103
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
M1 - 109793
ER -