title: Internalization of nanopolymeric tracers does not alter characteristics of placental cells.
abstract: In the cell therapy scenario, efficient tracing of transplanted cells is essential for investigating cell migration and interactions with host tissues. This is fundamental to provide mechanistic insights which altogether allow for the understanding of the translational potential of placental cell therapy in the clinical setting. Mesenchymal stem/stromal cells (MSC) from human placenta are increasingly being investigated for their potential in treating patients with a variety of diseases. In this study, we investigated the feasibility of using poly (methyl methacrylate) nanoparticles (PMMA-NPs) to trace placental MSC, namely those from the amniotic membrane (hAMSC) and early chorionic villi (hCV-MSC). We report that PMMP-NPs are efficiently internalized and retained in both populations, and do not alter cell morphofunctional parameters. We observed that PMMP-NP incorporation does not alter in vitro immune modulatory capability of placental MSC, a characteristic central to their reparative/therapeutic effects in vitro. We also show that in vitro, PMMP-NP uptake is not affected by hypoxia. Interestingly, after in vivo brain ischaemia and reperfusion injury achieved by transient middle cerebral artery occlusion (tMCAo) in mice, iv hAMSC treatment resulted in significant improvement in cognitive function compared to PBS-treated tMCAo mice. Our study provides evidence that tracing placental MSC with PMMP-NPs does not alter their in vitro and in vivo functions. These observations are grounds for the use of PMMP-NPs as tools to investigate the therapeutic mechanisms of hAMSC and hCV-MSC in preclinical models of inflammatory-driven diseases.
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bigini
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Elisa R
authors.initials: ER
authors.lastname: Zanier
authors.affiliation: R&D Unit, TOMA Advanced Biomedical Assays S.p.A., Busto Arsizio, Varese, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Saragozza
authors.affiliation: R&D Unit, TOMA Advanced Biomedical Assays S.p.A., Busto Arsizio, Varese, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Maciotta
authors.affiliation: Centro di Ricerca "E. Menni", Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Romele
authors.affiliation: Centro di Ricerca "E. Menni", Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonassi Signoroni
authors.affiliation: Centro di Ricerca "E. Menni", Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Silini
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pischiutta
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.|Fondazione IRCCS-Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Sammali
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Balducci
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Martina B
authors.initials: MB
authors.lastname: Violatto
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Talamini
authors.affiliation: Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Garry
authors.affiliation: Department of Chemistry, Material and Chemical Engineering, "Giulio Natta" Politecnico di Milano, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Moscatelli
authors.affiliation: Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: De Simoni
authors.affiliation: R&D Unit, TOMA Advanced Biomedical Assays S.p.A., Busto Arsizio, Varese, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Maggi
authors.affiliation: R&D Unit, TOMA Advanced Biomedical Assays S.p.A., Busto Arsizio, Varese, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Simoni
authors.affiliation: R&D Unit, TOMA Advanced Biomedical Assays S.p.A., Busto Arsizio, Varese, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Grati
authors.affiliation: Centro di Ricerca "E. Menni", Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Parolini
mesh_terms: D000650:Amnion / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D002824:Chorionic Villi / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D006801:Humans; D056747:Immunomodulation; D007511:Ischemia / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010641:Phenotype; D010920:Placenta / Q000166:cytology*; D011108:Polymers / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D011108:Polymers
keywords: amnion; cell tracing; chorion; hypoxia; ischaemia; mesenchymal stem/stromal cells; nanoparticles; placenta