Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism

Detalhes bibliográficos
Autor(a) principal: Vasconcelos M, Pedro De
Data de Publicação: 2022
Outros Autores: Lacerda, João
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/55244
Resumo: Copyright © 2022 de Vasconcelos and Lacerda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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spelling Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolismBrain repairDemyelination diseasesHematopoietic stem cell gene therapyHematopoietic stem cell transplantationLeukodystrophyMicrogliaNeurological disorderCopyright © 2022 de Vasconcelos and Lacerda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Hematopoietic stem cells have been investigated and applied for the treatment of certain neurological disorders for a long time. Currently, their therapeutic potential is harnessed in autologous and allogeneic hematopoietic stem cell transplantation (HSCT). Autologous HSCT is helpful in immune-mediated neurological diseases such as Multiple Sclerosis. However, clinical benefits derive more from the immunosuppressive conditioning regimen than the interaction between stem cells and the nervous system. Mainly used for hematologic malignancies, allogeneic HSCT explores the therapeutic potential of donor-derived hematopoietic stem cells. In the neurological setting, it has proven to be most valuable in Inborn Errors of Metabolism, a large spectrum of multisystem disorders characterized by congenital deficiencies in enzymes involved in metabolic pathways. Inborn Errors of Metabolism such as X-linked Adrenoleukodystrophy present with brain accumulation of enzymatic substrates that result in progressive inflammatory demyelination. Allogeneic HSCT can halt ongoing inflammatory neural destruction by replacing hematopoietic-originated microglia with donor-derived myeloid precursors. Microglia, the only neural cells successfully transplanted thus far, are the most valuable source of central nervous system metabolic correction and play a significant role in the crosstalk between the brain and hematopoietic stem cells. After transplantation, engrafted donor-derived myeloid cells modulate the neural microenvironment by recapitulating microglial functions and enhancing repair mechanisms such as remyelination. In some disorders, additional benefits result from the donor hematopoietic stem cell secretome that cross-corrects neighboring neural cells via mannose-6-phosphatase paracrine pathways. The limitations of allogeneic HSCT in this setting relate to the slow turnover of microglia and complications such as graft-vs.-host disease. These restraints have accelerated the development of hematopoietic stem cell gene therapy, where autologous hematopoietic stem cells are collected, manipulated ex vivo to overexpress the missing enzyme, and infused back into the patient. With this cellular drug vehicle strategy, the brain is populated by improved cells and exposed to supraphysiological levels of the flawed protein, resulting in metabolic correction. This review focuses on the mechanisms of brain repair resulting from HSCT and gene therapy in Inborn Errors of Metabolism. A brief mention will also be made on immune-mediated nervous system diseases that are treated with this approach.FrontiersRepositório da Universidade de LisboaVasconcelos M, Pedro DeLacerda, João2022-11-25T15:06:46Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55244engFront Cell Neurosci. 2022 May 26;16:89551110.3389/fncel.2022.8955111662-5102info: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:RCAAP2023-11-08T17:02:04Zoai:repositorio.ul.pt:10451/55244Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:55.759742Repositório 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 Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
title Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
spellingShingle Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
Vasconcelos M, Pedro De
Brain repair
Demyelination diseases
Hematopoietic stem cell gene therapy
Hematopoietic stem cell transplantation
Leukodystrophy
Microglia
Neurological disorder
title_short Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
title_full Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
title_fullStr Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
title_full_unstemmed Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
title_sort Hematopoietic stem cell transplantation for neurological disorders: a focus on inborn errors of metabolism
author Vasconcelos M, Pedro De
author_facet Vasconcelos M, Pedro De
Lacerda, João
author_role author
author2 Lacerda, João
author2_role author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Vasconcelos M, Pedro De
Lacerda, João
dc.subject.por.fl_str_mv Brain repair
Demyelination diseases
Hematopoietic stem cell gene therapy
Hematopoietic stem cell transplantation
Leukodystrophy
Microglia
Neurological disorder
topic Brain repair
Demyelination diseases
Hematopoietic stem cell gene therapy
Hematopoietic stem cell transplantation
Leukodystrophy
Microglia
Neurological disorder
description Copyright © 2022 de Vasconcelos and Lacerda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-25T15:06:46Z
2022
2022-01-01T00:00:00Z
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/10451/55244
url http://hdl.handle.net/10451/55244
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front Cell Neurosci. 2022 May 26;16:895511
10.3389/fncel.2022.895511
1662-5102
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 Frontiers
publisher.none.fl_str_mv Frontiers
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
instname_str 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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