Föreläsningar och seminarier Seminarium med Prof. Laura Calzà: "Oligodendrocyte precursor cells and remyelination: from embryology to neurorepair"

Oligodendrocyte precursor cells and remyelination: from embryology to neurorepair

Talare

Prof. Laura Calzà, Department of Pharmacy and Biotechnology, University of Bologna, Italy

MD, specialist in Endocrinology, full professor at the University of Bologna at the Department of Pharmacy and Biotechnology where she teaches Cognitive Sciences, Embryology, Regenerative Medicine. Founder of TransMed Research srl, test facility GLP-approved. Main research interests: Neurodegenerative diseases, Regenerative medicine, and Innovative healthcare solutions. Author of more than 270 original publications and book chapters (H-index 45 – Scopus).

Abstract

One of the most revolutionary discovery during the last decades has been the identification of stem/progenitors and precursor cells in the CNS of adult vertebrates, including humans. Moreover, a new cell population in the CNS was identify and defined as “NG2-positive” cell or “polydendrocytes”, and finally named Oligodendrocyte Precursor/Progenitor Cells (OPCs). OPCs are generated during development as precursors of oligodendrocytes (OL), and a pool of undifferentiated precursors remains all over the mature CNS. These quiescent unipotent stem cells can be activated by different stimuli able to trigger the proliferation, migration, and differentiation process once more, allowing the myelin repair and axonal re-myelination, thus indirectly contributing to neuroprotection. Remyelination is currently the only known self-repair ability of the CNS, potentially providing full anatomical and functional neuroregeneration.

Over the past years, our laboratory has been actively involved in the study of OPCs biology during development, adulthood and in pathological conditions, taking the opportunity to study an immature cell able to resume embryonic molecular signature in the context of a mature and stabilized microenvironment. We focused on the role of nuclear receptors (thyroid hormone and retinoic acid receptors) on OPCs biology, also in view of the myelination enhancing therapies. The metabolic profile of these cells during differentiation stages, and the role of nuclear receptors (thyroid hormone nuclear receptors and retinoic acid receptors) in this process will be reviewed, focusing on OPCs cycle exit and terminal differentiation induction.

Considering the importance of an appropriate thyroid hormone (TH) signaling during brain development and myelin formation, our laboratory proposed a TH supplementation as re-myelination enhancing therapy. Data supporting this indication will be reviewed, focusing on (i) effect of inflammation on TH metabolism in the CNS; (ii) effect of inflammation on OPCs differentiation; (iii) effects of exogenous TH administration on myelin repair in experimental models of demyelinating diseases in rodents and non-human primate. Moreover, TH therapeutic use will be also discussed in the contest of multidrug therapy and considering biomaterial-based strategies for local TH delivery by drug-loaded implantable electrospun devices and nanoparticle assisted drug delivery.

Utvalda publikationer

Differential effects of glucose deprivation on the survival of fetal versus adult neural stem cells-derived oligodendrocyte precursor cells.
Baldassarro VA, Marchesini A, Giardino L, Calzà L
Glia 2020 05;68(5):898-917

The role of nuclear receptors in the differentiation of oligodendrocyte precursor cells derived from fetal and adult neural stem cells.
Baldassarro VA, Krężel W, Fernández M, Schuhbaur B, Giardino L, Calzà L
Stem Cell Res 2019 05;37():101443

A Novel Three-Dimensional Culture Device Favors a Myelinating Morphology of Neural Stem Cell-Derived Oligodendrocytes.
Flagelli A, Candini O, Frabetti S, Dominici M, Giardino L, Calzà L, Baldassarro VA
Front Cell Dev Biol 2021 ;9():759982

Triiodothyronine administration ameliorates the demyelination/remyelination ratio in a non-human primate model of multiple sclerosis by correcting tissue hypothyroidism.
D'Intino G, Lorenzini L, Fernandez M, Taglioni A, Perretta G, Del Vecchio G, Villoslada P, Giardino L, Calzà L
J Neuroendocrinol 2011 Sep;23(9):778-90

Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System.
Bighinati A, Focarete ML, Gualandi C, Pannella M, Giuliani A, Beggiato S, Ferraro L, Lorenzini L, Giardino L, Calzà L
J Neurotrauma 2020 08;37(15):1708-1719