ArticleDisease models & mechanisms2014
Modelling of a targeted nanotherapeutic 'stroma' to deliver the cytokine LIF, or XAV939, a potent inhibitor of Wnt-β-catenin signalling, for use in human fetal dopaminergic grafts in Parkinson's disease.
Article in Disease models & mechanisms, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Exosomes Regulate the NLRP3/Caspase-1/IL-1β Signaling Pathway in Parkinson's Disease: Mechanisms of Neuroinflammation Modulation and α-Synuclein Propagation.Neuropsychiatric disease and treatment · 2026Review
- Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Neural stem cells for Parkinson's disease management: Challenges, nanobased support, and prospects.World journal of stem cells · 2023Review
- Efficacy of leukemia inhibitory factor as a therapeutic for permanent large vessel stroke differs among aged male and female rats.Brain research · 2019Article
- Neuroregeneration in Parkinson's Disease: From Proteins to Small Molecules.Current neuropharmacology · 2019Review
- Leukemia Inhibitory Factor Receptor Is Involved in Apoptosis in Rat Astrocytes Exposed to Oxygen-Glucose Deprivation.BioMed research international · 2019Article
- Neurodegenerative Disease: A Perspective on Cell-Based Therapy in the New Era of Cell-Free Nano-Therapy.Current pharmaceutical design · 2017Review
- Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2015Article
- Myelin repair in vivo is increased by targeting oligodendrocyte precursor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF).Biomaterials · 2015Article
- Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson's disease models.International journal of nanomedicine · 2015Review
- Multiple Sclerosis and the LIF/IL-6 Axis: Use of Nanotechnology to Harness the Tolerogenic and Reparative Properties of LIF.NanobiomedicineReview
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The endogenous reparative capacity of the adult human brain is low, and chronic neurodegenerative disorders of the central nervous system represent one of the greatest areas of unmet clinical need in the developing world. Novel therapeutic strategies to treat them include: (i) growth factor delivery to boost endogenous repair and (ii) replacement cell therapy, including replacing dopaminergic neurons to treat Parkinson's disease (PD). However, these approaches are restricted not only by rapid degradation of growth factors, but also by the limited availability of cells for transplant and the poor survival of implanted cells that lack the necessary stromal support. We therefore hypothesised that provision of a transient artificial stroma for paracrine delivery of pro-survival factors could overcome both of these issues. Using leukaemia inhibitory factor (LIF) - a proneural, reparative cytokine - formulated as target-specific poly(lactic-co-glycolic acid) (PLGA) nano-particles (LIF-nano-stroma), we discovered that attachment of LIF-nano-stroma to freshly isolated fetal dopaminergic cells improved their survival fourfold: furthermore, in vivo, the number of surviving human fetal dopaminergic cells tended to be higher at 3 months after grafting into the striatum of nude rats, compared with controls treated with empty nanoparticles. In addition, we also analysed the effect of a novel nano-stroma incorporating XAV939 (XAV), a potent inhibitor of the developmentally important Wnt-β-catenin signalling pathway, to investigate whether it could also promote the survival and differentiation of human fetal dopaminergic precursors; we found that the numbers of both tyrosine-hydroxylase-positive neurons (a marker of dopaminergic neurons) and total neurons were increased. This is the first demonstration that LIF-nano-stroma and XAV-nano-stroma each have pro-survival effects on human dopaminergic neurons, with potential value for target-specific modulation of neurogenic fate in cell-based therapies for PD.
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