title: Longitudinal tracking of triple labeled umbilical cord derived mesenchymal stromal cells in a mouse model of Amyotrophic Lateral Sclerosis.
abstract: The translational potential of cell therapy to humans requires a deep knowledge of the interaction between transplanted cells and host tissues. In this study, we evaluate the behavior of umbilical cord mesenchymal stromal cells (UC-MSCs), labeled with fluorescent nanoparticles, transplanted in healthy or early symptomatic transgenic SOD1G93A mice (a murine model of Amyotrophic Lateral Sclerosis). The double labeling of cells with nanoparticles and Hoechst-33258 enabled their tracking for a long time in both cells and tissues. Whole-body distribution of UC-MSCs was performed by in-vivo and ex-vivo analyses 1, 7, 21 days after single intravenous or intracerebroventricular administration. By intravenous administration cells were sequestered by the lungs and rapidly cleared by the liver. No difference in biodistribution was found among the two groups. On the other hand, UC-MSCs transplanted in lateral ventricles remained on the choroid plexus for the whole duration of the study even if decreasing in number. Few cells were found in the spinal cord of SOD1G93A mice exclusively. No migration in brain parenchyma was observed. These results suggest that the direct implantation in brain ventricles allows a prolonged permanence of cells close to the damaged areas and makes this method of tracking reliable for future studies of efficacy.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy. Electronic address: martina.violatto@marionegri.it.
authors.forename: Martina Bruna
authors.initials: MB
authors.lastname: Violatto
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Santangelo
authors.affiliation: USS Centro di Terapia Cellulare "G. Lanzani", A. O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Capelli
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Frapolli
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Sitia
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tortarolo
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Talamini
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Previdi
authors.affiliation: Dipartimento di Chimica, Materiali e Ingegneria Chimica "G. Natta", Politecnico di Milano, Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Moscatelli
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: USS Centro di Terapia Cellulare "G. Lanzani", A. O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Introna
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bendotti
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bigini
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000628:therapy*; D000818:Animals; D048429:Cell Size; D058948:Cell Tracking; D004195:Disease Models, Animal; D006801:Humans; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D013194:Staining and Labeling; D014018:Tissue Distribution; D014470:Umbilical Cord / Q000166:cytology*
keywords: Amyotrophic Lateral Sclerosis; Cell tracking; In vivo imaging; Mesenchymal stromal cells; Nanotechnology; Umbilical cord