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.
abstract: 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.
authors.affiliation: 1. Department of Pharmacology, Paraná Federal University, Curitiba, Paraná, Brazil;
authors.forename: Caroline Santos
authors.initials: CS
authors.lastname: Capitelli
authors.affiliation: 2. Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.
authors.forename: Carolina Salomão
authors.initials: CS
authors.lastname: Lopes
authors.affiliation: 2. Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.
authors.forename: Angélica Cristina
authors.initials: AC
authors.lastname: Alves
authors.affiliation: 1. Department of Pharmacology, Paraná Federal University, Curitiba, Paraná, Brazil;
authors.forename: Janaína
authors.initials: J
authors.lastname: Barbiero
authors.affiliation: 2. Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.
authors.forename: Lucas Felipe
authors.initials: LF
authors.lastname: Oliveira
authors.affiliation: 2. Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.
authors.forename: Valdo José Dias
authors.initials: VJ
authors.lastname: da Silva
authors.affiliation: 1. Department of Pharmacology, Paraná Federal University, Curitiba, Paraná, Brazil;
authors.forename: Maria Aparecida Barbato Frazão
authors.initials: MA
authors.lastname: Vital
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase
keywords: Bone marrow mononuclear cells; Cell therapy.; MPTP; Mesenchymal stem cells; Parkinson's disease