Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration.

Stem cell therapy for retinal degenerative diseases has been extensively tested in preclinical and clinical studies. However, preclinical studies performed in animal models at the early stage of disease do not optimally translate to patients that present to the clinic at a later stage of disease. As the retina degenerates, inflammation and oxidative stress increase and trophic factor support declines. Testing stem cell therapies in animal models at a clinically relevant stage is critical for translation to the clinic. Human neural progenitor cells (hNPC) and hNPC engineered to stably express GDNF (hNPCGDNF) were subretinally injected into the Royal College of Surgeon (RCS) rats, a well-established model for retinal degeneration, at early and later stages of the disease. hNPCGDNF treatment at the early stage of retinal degeneration provided enhanced visual function compared to hNPC alone. Treatment with both cell types resulted in preserved retinal morphology compared to controls. hNPCGDNF treatment led to significantly broader photoreceptor protection than hNPC treatment at both early and later times of intervention. The phagocytic role of hNPC appears to support RPE cell functions and the secreted GDNF offers neuroprotection and enables the extended survival of photoreceptor cells in transplanted animal eyes. Donor cells in the RCS rat retina survived with only limited proliferation, and hNPCGDNF produced GDNF in vivo. Cell treatment led to significant changes in various pathways related to cell survival, antioxidative stress, phagocytosis, and autophagy. A combined stem cell and trophic factor therapy holds great promise for treating retinal degenerative diseases including retinitis pigmentosa and age-related macular degeneration.

Human iPSC-derived neural progenitor cells secreting GDNF provide protection in rodent models of ALS and retinal degeneration.

Human induced pluripotent stem cells (iPSCs) are a renewable cell source that can be differentiated into neural progenitor cells (iNPCs) and transduced with glial cell line-derived neurotrophic factor (iNPC-GDNFs). The goal of the current study is to characterize iNPC-GDNFs and test their therapeutic potential and safety. Single-nuclei RNA-seq show iNPC-GDNFs express NPC markers. iNPC-GDNFs delivered into the subretinal space of the Royal College of Surgeons rodent model of retinal degeneration preserve photoreceptors and visual function. Additionally, iNPC-GDNF transplants in the spinal cord of SOD1G93A amyotrophic lateral sclerosis (ALS) rats preserve motor neurons. Finally, iNPC-GDNF transplants in the spinal cord of athymic nude rats survive and produce GDNF for 9 months, with no signs of tumor formation or continual cell proliferation. iNPC-GDNFs survive long-term, are safe, and provide neuroprotection in models of both retinal degeneration and ALS, indicating their potential as a combined cell and gene therapy for various neurodegenerative diseases.

Simultaneous removal of PAHs and metal contaminants from water using magnetic nanoparticle adsorbents.

Many industrial wastewaters are contaminated with both heavy metal ions and organic compounds, posing a major threat to public health and the environment. In this study, magnetic nanoparticle adsorbents, namely Mag-PCMA-T, which contain a maghemite core and a silica mesoporous layer that permanently confines surfactant micelles within the mesopores, were synthesized to achieve simultaneous removal of polycyclic aromatic hydrocarbons (PAHs) (1mg/L) and metal contaminants (1mg/L). The individual removal efficiency of Cd(2+) and acenaphthene using Mag-PCMA-T was evaluated under a range of initial ion concentrations and adsorbent dosages, as well as the competitive adsorption with Cd(2+) and acenaphthene simultaneously present. The isotherms and kinetics of Cd(2+) and acenaphthene sorption onto Mag-PCMA-T were determined. Mag-PCMA-T removed >85% of the acenaphthene in <30min, with relatively high sorption capacity (up to 1060mg/kg). Mag-PCMA-T also exhibited high sorption capacity for Cd(2+) (up to 2250mg/kg). The simultaneous sorption performance was stable across a wide pH range (4-9) as well as in the presence of competitive metal ions (Ca(2+) and Mg(2+)) or natural organic matters. The Mag-PCMA-T can be regenerated and reused, providing a sustainable, fast, convenient, and efficient approach for water treatment.