Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pat...

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Main Authors: Lucía Calatrava-Ferreras, Rafael Gonzalo-Gobernado, Antonio S. Herranz, Diana Reimers, Teresa Montero Vega, Adriano Jiménez-Escrig, Luis Alberto Richart López, Eulalia Bazán
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2012/135187
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author Lucía Calatrava-Ferreras
Rafael Gonzalo-Gobernado
Antonio S. Herranz
Diana Reimers
Teresa Montero Vega
Adriano Jiménez-Escrig
Luis Alberto Richart López
Eulalia Bazán
author_facet Lucía Calatrava-Ferreras
Rafael Gonzalo-Gobernado
Antonio S. Herranz
Diana Reimers
Teresa Montero Vega
Adriano Jiménez-Escrig
Luis Alberto Richart López
Eulalia Bazán
author_sort Lucía Calatrava-Ferreras
collection DOAJ
description Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders.
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spelling doaj-art-85d2d180b12a475eb7590abdd38676692025-02-03T01:03:19ZengWileyStem Cells International1687-966X1687-96782012-01-01201210.1155/2012/135187135187Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned RatsLucía Calatrava-Ferreras0Rafael Gonzalo-Gobernado1Antonio S. Herranz2Diana Reimers3Teresa Montero Vega4Adriano Jiménez-Escrig5Luis Alberto Richart López6Eulalia Bazán7Servicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Bioquímica, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Neurología, Hospital Universitario Ramón y Cajal, 28034 Madrid, SpainCentro de Transfusiones de la Comunidad de Madrid, Valdebernardo, 28030 Madrid, SpainServicio de Neurobiología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainCerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders.http://dx.doi.org/10.1155/2012/135187
spellingShingle Lucía Calatrava-Ferreras
Rafael Gonzalo-Gobernado
Antonio S. Herranz
Diana Reimers
Teresa Montero Vega
Adriano Jiménez-Escrig
Luis Alberto Richart López
Eulalia Bazán
Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats
Stem Cells International
title Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats
title_full Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats
title_fullStr Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats
title_full_unstemmed Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats
title_short Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats
title_sort effects of intravenous administration of human umbilical cord blood stem cells in 3 acetylpyridine lesioned rats
url http://dx.doi.org/10.1155/2012/135187
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