Intrastriatal transplantation of human dental pulp stem cells improves motor function and attenuates nigrostriatal injury in a 6-hydroxydopamine rat model of Parkinson's disease
Intrastriatal transplantation of human dental pulp stem cells improves motor function and attenuates nigrostriatal injury in a 6-hydroxydopamine rat model of Parkinson's disease
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
A plain-language reading has not been prepared for this paper yet.
Original abstract
Background: Parkinson’s disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic system, and increasing evidence implicates neuroinflammation and oxidative stress as major drivers of disease progression. Human dental pulp stem cells (hDPSCs) possess neurotrophic and immunomodulatory properties; however, their therapeutic effects following intrastriatal delivery have not been sufficiently defined.Methods: A rat model of Parkinson's disease was created using unilateral 6-hydroxydopamine (6-OHDA), followed by the intrastriatal transplantation of human dental pulp stem cells (hDPSCs). Motor behavior was assessed using apomorphine-induced rotation and open field testing. To assess nigrostriatal damage and gliosis, immunofluorescence techniques were employed using tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1).Complementary Transwell co-culture experiments were used to examine hDPSC effects on lipopolysaccharide (LPS)-stimulated BV-2 microglia, intracellular reactive oxygen species (ROS), apoptosis-associated proteins, inflammatory mediators, and AKT/glycogen synthase kinase-3beta (GSK3β) signaling.Results: hDPSC transplantation significantly reduced rotational asymmetry and improved spontaneous locomotor activity in mice. In vivo, hDPSCs attenuated the loss of TH immunoreactivity in the substantia nigra pars compacta and reduced astroglial and microglial reactivity in the striatum. In vitro, hDPSCs decreased the iNOS-dominant microglial phenotype, increased Arg1-positive cells, reduced reactive oxygen species accumulation, and partially normalized inflammation- and apoptosis-related protein profiles. These effects were accompanied by increased AKT phosphorylation and increased inhibitory phosphorylation of GSK3β at Ser9.Conclusions: Intrastriatal hDPSC transplantation ameliorated motor deficits and nigrostriatal injury through multimodal actions converging on microglial reprogramming, oxidative–apoptotic restraint, and AKT/GSK3β-associated signaling. These findings support hDPSCs as promising candidates for further preclinical development in PD and justify additional causality-oriented and graft-persistence studies.