FisMat2017 - Submission - View

Abstract's title: Multiscale X-Ray Phase Contrast Tomography investigation of animal model of multiple sclerosis: monitoring diseases and treatment efficacy
Submitting author: Lorenzo Massimi
Affiliation: Institute of Nanotechnology- CNR, Rome Unit
Affiliation Address: CNR - Nanotec sede Di Roma presso Dip. di Fisica Università di Roma la Sapienza P.le Aldo Moro 5, 00185, Roma
Country: Italy
Oral presentation/Poster (Author's request): Oral presentation
Other authors and affiliations: Michela Fratini (Institute of Nanotechnology- CNR, Rome Unit, Rome, Italy, IRCCS Fondazione Santa Lucia, Roma) Inna Bukreeva (Institute of Nanotechnology- CNR, Rome Unit, Rome, Italy) Francesco Brun (Institute of Nanotechnology- CNR, Rome Unit, Rome, Italy) Alberto Mittone (European Synchrotron Radiation Facility, Grenoble, Cedex 9, France) Alberto Bravin (European Synchrotron Radiation Facility, Grenoble, Cedex 9, France) Nicole Kerlero de Rosbo (Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Unit, University of Genoa & AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro Genoa, Italy) Antonio Uccelli (Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Unit, University of Genoa & AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro Genoa, Italy) Alessia Cedola (Institute of Nanotechnology- CNR, Rome Unit, Rome, Italy, IRCCS Fondazione Santa Lucia, Roma)
Abstract

Multiple sclerosis (MS) is neurodegenerative disease affecting about 2,5 million of people in the world. Most people are diagnosed between the ages of 20 and 40 and course is rarely predictable. Unfortunately, etiology of MS is still unclear and no efficient therapy to stop or at least reduce progression of the disease exists [1].

Experimental Autoimmune Encephalomyelitis (EAE) represents the animal model for MS. Such as MS it is an autoimmune disease of the central nervous system (CNS) driven by autoreactive myelin-specific T cells that infiltrate through an impaired blood-brain barrier (BBB) leading to neuroinflammation and resulting in demyelination and irreversible axonal loss. Entranceof inflammatory cells into the CNS by increasing permeability in BBB reveals the strict interplay existing between vascular alterations and development of immune-mediated CNS diseases needing for a simultaneous investigation of vascular network (VN) and neuronal network (NN). An innovative therapy based on mesenchymal stem cells (MSC) is currently under investigation. MSC are being considered as an alternative therapeutic in view of their potential regulatory effect on immune cells, as well as their neuroprotective features [2, 3].

To elucidate mechanism behind progression of EAE disease and MSC therapy we present quantitative characterization of VN and NN up to cellular level by means of multiscale (micro and nano) x-ray phase contrast tomography (XPCT) in ex-vivo lumbar region of mouse spinal cord. In contrast with conventional 2D images that needs sample sectioning and magnetic resonance imaging that is limited in spatial resolution, XPCT can provide micron and sub-micron volumetric information on a very large field of view covering whole spinal cord or brain, with large potential in the assessment of complex relation existing between VN and NN [4]. We observed alteration in vascular network one day after disease onset and subsequent modification due to an angiogenic response. In comparison mice administrated with MSC therapy preserve a reduced insult to VN. Moreover, we were capable to determine also faith of neurons [5]. With progression of the disease a decreasing of numbers of neurons is observed while administration of MSC therapy slows down neuronal loss demonstrating protection exerted by therapy. Our results demonstrate that phase contrast tomography is raising as valuable tool for pre-clinical studies new insights in EAE disease and MSC-based therapy going beyond the current knowledge.

[1] McDonald et al. Annals of neurology 50.1 (2001): 121-127

[2] Laroni, A et al. J. Neuroimmune Pharmacol. 2013:8:1062-76.

[3] Uccelli A. et al. Nat Rev Immunol. 2008;8:726-36

[4] Michela Fratini, M. et al. Sci Rep.2015;5:8514.

[5] Bukreeva, I., et al.  Sci Rep 7 (2017): 41054.