Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

Abstract

BackgroundMesenchymal stem cells (MSCs) are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α) is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg) was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively) or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA) assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining.ResultsRats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH)-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc) compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups.ConclusionsConsequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

The Intrathecal Infusion of Mesenchymal Stem Cells into Healthy Rabbits is Safe and Devoid of Neurological or Clinical Complications

“…Consequently, our results showing that intrathecal infusion of MSC is safe and feasible, in addition to data demonstrating MSC survival/ migration within the CNS [6,13] and effectiveness in neurological recovery [6,15], epitomize a weighty foundation for their use in the treatment of neurological patients.…”

“…The above assertion is supported by three major facts: a) MSC can differentiate outside the mesenchymal lineage into neurological precursors [5,9,10], b) after infusion of MSC to animals with genetic or experimental neurological diseases, MSC migrate and survive within the central nervous system [6,11] and contribute to the improvement/recovery of pre-symptomatic motor functions [6,7,[11][12][13] and c) MSC secrete several growth factors and chemokines that may create a neuroprotective environment favorable for tissue sparing and axonal regeneration [14,15 ].…”

Mesenchymal Stromal Cells and Neural Stem Cells Potential for Neural Repair in Spinal Cord Injury and Human Neurodegenerative Disorders

“…Moreover, a significant improvement in behavioral motor tests in hMSCs treated group has also been observed (Park et al 2008). In vitro study demonstrated that SDF--1, chemokine constitutively produced by MSCs increased dopamine release and led to suppression of cell death induced by 6-OHDA administration compared to untreated group (Wang et al 2010). Neuroprotective effect of hMSCs on dopaminergic neurons mediated by anti-inflammatory properties of MSCs and their modulation of microglial activation were uncovered ).…”

Cell-based neurorestorative therapy for postpoliomyelitis syndrome: a case report

“…The potential mechanisms for functional recovery of PPS by cell-based neurorestorative therapy are as follows: implanted cells may secrete some neurotrophic factors for the impaired neurons 29 ; implanted olfactory ensheathing cells may promote axonal regeneration and remyelination 30,31 ; moreover, it is possible that the implanted cells may change the internal neuromuscular environment and stimulate autologous stem cells to secrete factors. 32,33 This is the first clinical report of a PPS patient treated by cell-based neurorestorative therapy, which showed some promising results.…”