Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/74317 |
Resumo: | Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn<sup>2+</sup>) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn<sup>2+</sup> alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn<sup>2+</sup>-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn<sup>2+</sup> alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time. |
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Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cellsHydrogelManganeseContrast agentBiomaterialIntrathecalLarge animalsScience & TechnologyCell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn<sup>2+</sup>) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn<sup>2+</sup> alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn<sup>2+</sup>-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn<sup>2+</sup> alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time.This research was funded by The National Centre for Research and Development, grant number 12/EuroNanoMed/2016.Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoKalkowski, LukaszGolubczyk, DominikaKwiatkowska, JoannaHolak, PiotrMilewska, KamilaJanowski, MiroslawOliveira, Joaquim M.Walczak, PiotrMalysz-Cymborska, Izabela2021-07-132021-07-13T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/74317engKalkowski, L.; Golubczyk, D.; Kwiatkowska, J.; Holak, P.; Milewska, K.; Janowski, M.; Oliveira, J.M.; Walczak, P.; Malysz-Cymborska, I. Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells. Pharmaceutics 2021, 13, 1076. https://doi.org/10.3390/pharmaceutics130710761999-492310.3390/pharmaceutics13071076https://www.mdpi.com/1999-4923/13/7/1076info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:47:26Zoai:repositorium.sdum.uminho.pt:1822/74317Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:45:32.809845Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells |
title |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells |
spellingShingle |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells Kalkowski, Lukasz Hydrogel Manganese Contrast agent Biomaterial Intrathecal Large animals Science & Technology |
title_short |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells |
title_full |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells |
title_fullStr |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells |
title_full_unstemmed |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells |
title_sort |
Two in one: use of divalent manganese ions as both cross-linking and MRI contrast agent for intrathecal injection of hydrogel-embedded stem cells |
author |
Kalkowski, Lukasz |
author_facet |
Kalkowski, Lukasz Golubczyk, Dominika Kwiatkowska, Joanna Holak, Piotr Milewska, Kamila Janowski, Miroslaw Oliveira, Joaquim M. Walczak, Piotr Malysz-Cymborska, Izabela |
author_role |
author |
author2 |
Golubczyk, Dominika Kwiatkowska, Joanna Holak, Piotr Milewska, Kamila Janowski, Miroslaw Oliveira, Joaquim M. Walczak, Piotr Malysz-Cymborska, Izabela |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Kalkowski, Lukasz Golubczyk, Dominika Kwiatkowska, Joanna Holak, Piotr Milewska, Kamila Janowski, Miroslaw Oliveira, Joaquim M. Walczak, Piotr Malysz-Cymborska, Izabela |
dc.subject.por.fl_str_mv |
Hydrogel Manganese Contrast agent Biomaterial Intrathecal Large animals Science & Technology |
topic |
Hydrogel Manganese Contrast agent Biomaterial Intrathecal Large animals Science & Technology |
description |
Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn<sup>2+</sup>) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn<sup>2+</sup> alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn<sup>2+</sup>-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn<sup>2+</sup> alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-07-13 2021-07-13T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/74317 |
url |
http://hdl.handle.net/1822/74317 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Kalkowski, L.; Golubczyk, D.; Kwiatkowska, J.; Holak, P.; Milewska, K.; Janowski, M.; Oliveira, J.M.; Walczak, P.; Malysz-Cymborska, I. Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells. Pharmaceutics 2021, 13, 1076. https://doi.org/10.3390/pharmaceutics13071076 1999-4923 10.3390/pharmaceutics13071076 https://www.mdpi.com/1999-4923/13/7/1076 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133021002006528 |