Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Capitelli, Caroline Santos, Lopes, Carolina Salomão, Alves, Angélica Cristina, Barbiero, Janaína, Oliveira, Lucas Felipe, da Silva, Valdo José Dias, Vital, Maria Aparecida Barbato Frazão
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2014
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
_version_ 1782330965545189376
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
work_keys_str_mv AT capitellicarolinesantos oppositeeffectsofbonemarrowderivedcellstransplantationinmptpratmodelofparkinsonsdiseaseacomparisonstudyofmononuclearandmesenchymalstemcells
AT lopescarolinasalomao oppositeeffectsofbonemarrowderivedcellstransplantationinmptpratmodelofparkinsonsdiseaseacomparisonstudyofmononuclearandmesenchymalstemcells
AT alvesangelicacristina oppositeeffectsofbonemarrowderivedcellstransplantationinmptpratmodelofparkinsonsdiseaseacomparisonstudyofmononuclearandmesenchymalstemcells
AT barbierojanaina oppositeeffectsofbonemarrowderivedcellstransplantationinmptpratmodelofparkinsonsdiseaseacomparisonstudyofmononuclearandmesenchymalstemcells
AT oliveiralucasfelipe oppositeeffectsofbonemarrowderivedcellstransplantationinmptpratmodelofparkinsonsdiseaseacomparisonstudyofmononuclearandmesenchymalstemcells
AT dasilvavaldojosedias oppositeeffectsofbonemarrowderivedcellstransplantationinmptpratmodelofparkinsonsdiseaseacomparisonstudyofmononuclearandmesenchymalstemcells
AT vitalmariaaparecidabarbatofrazao oppositeeffectsofbonemarrowderivedcellstransplantationinmptpratmodelofparkinsonsdiseaseacomparisonstudyofmononuclearandmesenchymalstemcells