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Assessing NSC Transplantation as a Treatment Approach for Parkinson’s Disease in Aged Patients

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Review of “Neural Stem Cell Grafts Promote Astroglia‐Driven Neurorestoration in the Aged Parkinsonian Brain via Wnt/β‐Catenin Signaling” from STEM CELLS by Stuart P. Atkinson

The progressive loss of midbrain dopaminergic (mDA) neurons from the substantia nigra pars compacta (SNpc) and the resulting reduction in striatal dopamine [1] characterize Parkinson's disease (PD), the most common central nervous system (CNS) movement disorder. As current treatment approaches alleviate PD motor symptoms but do not affect on‐going neurodegeneration [2], studies have turned to advanced therapies involving the transplantation of neural stem cells (NSCs). Such therapies hope to provide local trophic support and immune modulation to complement the restorative responses of endogenous NSCs; however, we still lack a full understanding regarding the effects of NSC transplants on the aged PD brain.

New research led by Bianca Marchetti (University of Catania School, Italy) and Stefano Pluchino (University of Cambridge, UK) has now assessed the effects of unilateral transplantation of syngeneic somatic NSCs within the SNpc. In their STEM CELLS study, L'episcopo et al. report that NSC transplantation into the aged brain may represent an exciting treatment approach to reverse PD symptoms and highlight the critical role of astrocyte and Wnt/β‐catenin signaling in the restoration of nigrostriatal mDA neurons [3].

Transplanted syngeneic NSCs engrafted well within the aged SNpc and migrated towards the region that harbors self‐renewing NSCs endowed with dopaminergic (DA) potential (tegmental midbrain aqueduct periventricular regions) where a significant proportion (~30%) acquired an astroglial-like phenotype. Additionally, NSCs also underwent an mDA developmental program, acquiring a mature Nurr1+TH+ mDA-like phenotype. 

Interestingly, the authors discovered that both exogenous (NSC-derived) and endogenous astrocytes triggered Wnt/β‐catenin signaling in SNpc‐mDA neurons and microglia and this correlated well with the subsequent protection and rescue of mDA neurons, the modulation of the immune environment, and improvements in motor defects. Indeed, inhibition of Wnt/β‐catenin signaling eliminated NSC graft-mediated effects therapeutic effects, further highlighting the critical nature of this signaling pathway.

The authors note that their study further strengthens the implication of deregulated Wnt/β‐catenin signaling in PD (see the original article for extensive references) and suggest harnessing Wnt/β‐catenin signaling in transplanted NSCs as a novel treatment approach for PD in aged patients.

For more on NSC transplantation-based therapies for neurodegenerative disorders in aged subjects, stay tuned to the Stem Cells Portal!

References

  1. Hornykiewicz O, Parkinson's disease and the adaptive capacity of the nigrostriatal dopamine system: possible neurochemical mechanisms. Adv Neurol 1993;60:140-7.
  2. Olanow CW, Schapira AHV, and Agid Y, Neuroprotection for Parkinson's disease: Prospects and promises. Annals of Neurology 2003;53:S1-S2.
  3. L'Episcopo F, Tirolo C, Peruzzotti-Jametti L, et al., Neural Stem Cell Grafts Promote Astroglia-Driven Neurorestoration in the Aged Parkinsonian Brain via Wnt/β-Catenin Signaling. STEM CELLS 2018;36:1179-1197.