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.

Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats

“…It was previously reported that naïve, neurotrophic factorsecreting, or neurally induced MSCs have therapeutic effects when transplanted into 6-OHDA-or MPTP-induced Parkinsonian animals (Biju et al, 2013;Capitelli et al, 2014;Dezawa et al, 2004;Glavaski-Joksimovic et al, 2010;McCoy et al, 2008;Park et al, 2014;Sadan et al, 2009;Wang et al, 2013;Weiss et al, 2006;Yan et al, 2013). A beneficial effect of the striatal transplantation of both SHEDs and DAergic neuronlike SHEDs was also previously reported (Wang et al, 2010).…”

A Meta-Analysis of Mesenchymal Stem Cells in Animal Models of Parkinson's Disease

“…There were 20 experiments conducted to evaluate rotational behavior and 8 experiments conducted to evaluate limb function. In addition, there were three studies using the rotarod test [36,81,83] and three studies using the open field test [80,84,89]. Because of insufficient numbers, these studies on rotarod and open field were not included in the meta-analysis.…”

Comparative analysis of neural differentiation potential in human mesenchymal stem cells derived from chorion and adult bone marrow

“…Recently, bone marrow MSCs (BM-MSCs) have been reported to have the potential to develop into neural lineages such as those for neurons, astrocytes, and oligodendrocytes both in vivo (Eglitis and Mezey 1997;Kopen et al 1999, Lee et al 2013Capitelli et al 2014) and in vitro (SanchezRamos et al 2000;Woodbury et al 2000;Deng et al 2001). Some attempts to use MSCs for the treatment of CNS disorders have even been reported (Chopp et al 2000;Kang et al 2003;Joyce et al 2010;Momin et al 2010).…”