Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration

Abstract Stem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route, of st...

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Autores principales:	Izabela Malysz-Cymborska, Dominika Golubczyk, Lukasz Kalkowski, Joanna Kwiatkowska, Michal Zawadzki, Joanna Głodek, Piotr Holak, Joanna Sanford, Kamila Milewska, Zbigniew Adamiak, Piotr Walczak, Miroslaw Janowski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7418b613efca429b83753bd9a48ff63c
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spelling	oai:doaj.org-article:7418b613efca429b83753bd9a48ff63c2021-12-02T16:36:12ZIntra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration10.1038/s41598-021-85820-32045-2322https://doaj.org/article/7418b613efca429b83753bd9a48ff63c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85820-3https://doaj.org/toc/2045-2322Abstract Stem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route, of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Canine GRP transplantation in dogs resulted in rather poor retention in the brain, so MSCs were used in subsequent experiments. To evaluate the safety of MSC intraarterial transplantation, naïve pigs (n = 3) were used as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. The procedure in pigs has proven to be safe and histopathology has demonstrated the successful and predictable placement of transplanted porcine MSCs. Transplantation of canine MSCs in DM dogs resulted in their accumulation in the brain. Interventional and follow-up MRI proved the procedure was feasible and safe. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases.Izabela Malysz-CymborskaDominika GolubczykLukasz KalkowskiJoanna KwiatkowskaMichal ZawadzkiJoanna GłodekPiotr HolakJoanna SanfordKamila MilewskaZbigniew AdamiakPiotr WalczakMiroslaw JanowskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Izabela Malysz-Cymborska Dominika Golubczyk Lukasz Kalkowski Joanna Kwiatkowska Michal Zawadzki Joanna Głodek Piotr Holak Joanna Sanford Kamila Milewska Zbigniew Adamiak Piotr Walczak Miroslaw Janowski Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
description	Abstract Stem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route, of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Canine GRP transplantation in dogs resulted in rather poor retention in the brain, so MSCs were used in subsequent experiments. To evaluate the safety of MSC intraarterial transplantation, naïve pigs (n = 3) were used as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. The procedure in pigs has proven to be safe and histopathology has demonstrated the successful and predictable placement of transplanted porcine MSCs. Transplantation of canine MSCs in DM dogs resulted in their accumulation in the brain. Interventional and follow-up MRI proved the procedure was feasible and safe. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases.
format	article
author	Izabela Malysz-Cymborska Dominika Golubczyk Lukasz Kalkowski Joanna Kwiatkowska Michal Zawadzki Joanna Głodek Piotr Holak Joanna Sanford Kamila Milewska Zbigniew Adamiak Piotr Walczak Miroslaw Janowski
author_facet	Izabela Malysz-Cymborska Dominika Golubczyk Lukasz Kalkowski Joanna Kwiatkowska Michal Zawadzki Joanna Głodek Piotr Holak Joanna Sanford Kamila Milewska Zbigniew Adamiak Piotr Walczak Miroslaw Janowski
author_sort	Izabela Malysz-Cymborska
title	Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
title_short	Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
title_full	Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
title_fullStr	Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
title_full_unstemmed	Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
title_sort	intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7418b613efca429b83753bd9a48ff63c
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Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration

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