Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease

Background: Dysfunction of glia contributes to the deterioration of the central nervous system in a wide array of neurological disorders, thus global replacement of glia is very attractive. Human glial-restricted precursors (hGRPs) transplanted intraventricularly into neonatal mice extensively migra...

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Autores principales:	Luiza Stanaszek, Malgorzata Majchrzak, Katarzyna Drela, Piotr Rogujski, Joanna Sanford, Michal Fiedorowicz, Magdalena Gewartowska, Malgorzata Frontczak-Baniewicz, Piotr Walczak, Barbara Lukomska, Miroslaw Janowski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	GRPs glial-restricted precursors myelination MRI neurological disorders Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ff6fe2270a75449c84788a1f539202bb
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spelling	oai:doaj.org-article:ff6fe2270a75449c84788a1f539202bb2021-11-25T17:09:54ZMyelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease10.3390/cells101129682073-4409https://doaj.org/article/ff6fe2270a75449c84788a1f539202bb2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2968https://doaj.org/toc/2073-4409Background: Dysfunction of glia contributes to the deterioration of the central nervous system in a wide array of neurological disorders, thus global replacement of glia is very attractive. Human glial-restricted precursors (hGRPs) transplanted intraventricularly into neonatal mice extensively migrated and rescued the lifespan in half of the studied mice, whereas mouse GRPs (mGRPs) presented no therapeutic benefit. We studied in the same experimental setting canine GRPs (cGRP) to determine whether their therapeutic potential falls between hGRPs and mGRPs. Additional motivation for the selection of cGRPs was a potential for use in veterinary medicine. Methods: cGRPs were extracted from the brain of dog fetuses. The cells were transplanted into the anterior or posterior aspect of the lateral ventricle (LV) of neonatal, immunodeficient, dysmyelinated mice (<i>Mbp</i><sup>shi</sup>, <i>Rag2</i> KO; shiv/rag2). Outcome measures included early cell biodistribution, animal survival and myelination assessed with MRI, immunohistochemistry and electron microscopy. Results: Grafting of cGRP into posterior LV significantly extended animal survival, whereas no benefit was observed after anterior LV transplantation. In contrast, myelination of the corpus callosum was more prominent in anteriorly transplanted animals. Conclusions: The extended survival of animals after transplantation of cGRPs could be explained by the vicinity of the transplant near the brain stem.Luiza StanaszekMalgorzata MajchrzakKatarzyna DrelaPiotr RogujskiJoanna SanfordMichal FiedorowiczMagdalena GewartowskaMalgorzata Frontczak-BaniewiczPiotr WalczakBarbara LukomskaMiroslaw JanowskiMDPI AGarticleGRPsglial-restricted precursorsmyelinationMRIneurological disordersBiology (General)QH301-705.5ENCells, Vol 10, Iss 2968, p 2968 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GRPs glial-restricted precursors myelination MRI neurological disorders Biology (General) QH301-705.5
spellingShingle	GRPs glial-restricted precursors myelination MRI neurological disorders Biology (General) QH301-705.5 Luiza Stanaszek Malgorzata Majchrzak Katarzyna Drela Piotr Rogujski Joanna Sanford Michal Fiedorowicz Magdalena Gewartowska Malgorzata Frontczak-Baniewicz Piotr Walczak Barbara Lukomska Miroslaw Janowski Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease
description	Background: Dysfunction of glia contributes to the deterioration of the central nervous system in a wide array of neurological disorders, thus global replacement of glia is very attractive. Human glial-restricted precursors (hGRPs) transplanted intraventricularly into neonatal mice extensively migrated and rescued the lifespan in half of the studied mice, whereas mouse GRPs (mGRPs) presented no therapeutic benefit. We studied in the same experimental setting canine GRPs (cGRP) to determine whether their therapeutic potential falls between hGRPs and mGRPs. Additional motivation for the selection of cGRPs was a potential for use in veterinary medicine. Methods: cGRPs were extracted from the brain of dog fetuses. The cells were transplanted into the anterior or posterior aspect of the lateral ventricle (LV) of neonatal, immunodeficient, dysmyelinated mice (<i>Mbp</i><sup>shi</sup>, <i>Rag2</i> KO; shiv/rag2). Outcome measures included early cell biodistribution, animal survival and myelination assessed with MRI, immunohistochemistry and electron microscopy. Results: Grafting of cGRP into posterior LV significantly extended animal survival, whereas no benefit was observed after anterior LV transplantation. In contrast, myelination of the corpus callosum was more prominent in anteriorly transplanted animals. Conclusions: The extended survival of animals after transplantation of cGRPs could be explained by the vicinity of the transplant near the brain stem.
format	article
author	Luiza Stanaszek Malgorzata Majchrzak Katarzyna Drela Piotr Rogujski Joanna Sanford Michal Fiedorowicz Magdalena Gewartowska Malgorzata Frontczak-Baniewicz Piotr Walczak Barbara Lukomska Miroslaw Janowski
author_facet	Luiza Stanaszek Malgorzata Majchrzak Katarzyna Drela Piotr Rogujski Joanna Sanford Michal Fiedorowicz Magdalena Gewartowska Malgorzata Frontczak-Baniewicz Piotr Walczak Barbara Lukomska Miroslaw Janowski
author_sort	Luiza Stanaszek
title	Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease
title_short	Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease
title_full	Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease
title_fullStr	Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease
title_full_unstemmed	Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease
title_sort	myelin-independent therapeutic potential of canine glial-restricted progenitors transplanted in mouse model of dysmyelinating disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ff6fe2270a75449c84788a1f539202bb
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Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease

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