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Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem ce...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135227/ https://www.ncbi.nlm.nih.gov/pubmed/25136260 http://dx.doi.org/10.7150/ijms.8182 |
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author | Capitelli, Caroline Santos Lopes, Carolina Salomão Alves, Angélica Cristina Barbiero, Janaína Oliveira, Lucas Felipe da Silva, Valdo José Dias Vital, Maria Aparecida Barbato Frazão |
author_facet | Capitelli, Caroline Santos Lopes, Carolina Salomão Alves, Angélica Cristina Barbiero, Janaína Oliveira, Lucas Felipe da Silva, Valdo José Dias Vital, Maria Aparecida Barbato Frazão |
author_sort | Capitelli, Caroline Santos |
collection | PubMed |
description | The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development. |
format | Online Article Text |
id | pubmed-4135227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-41352272014-08-18 Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells Capitelli, Caroline Santos Lopes, Carolina Salomão Alves, Angélica Cristina Barbiero, Janaína Oliveira, Lucas Felipe da Silva, Valdo José Dias Vital, Maria Aparecida Barbato Frazão Int J Med Sci Research Paper The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development. Ivyspring International Publisher 2014-08-03 /pmc/articles/PMC4135227/ /pubmed/25136260 http://dx.doi.org/10.7150/ijms.8182 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Capitelli, Caroline Santos Lopes, Carolina Salomão Alves, Angélica Cristina Barbiero, Janaína Oliveira, Lucas Felipe da Silva, Valdo José Dias Vital, Maria Aparecida Barbato Frazão Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells |
title | Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells |
title_full | Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells |
title_fullStr | Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells |
title_full_unstemmed | Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells |
title_short | Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson's Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells |
title_sort | opposite effects of bone marrow-derived cells transplantation in mptp-rat model of parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135227/ https://www.ncbi.nlm.nih.gov/pubmed/25136260 http://dx.doi.org/10.7150/ijms.8182 |
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