Aggregation-induced emission (AIE) nanoparticles labeled human embryonic stem cells (hESCs)-derived neurons for transplantation.

Transplantation of differentiated neurons derived from either human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) is an emerging therapeutic strategy for various neurodegenerative diseases. One important aspect of transplantation is the accessibility to track and control the activity of the stem cells-derived neurons post-transplantation. Recently, the characteristics of organic nanoparticles (NPs) with aggregation-induced emission (AIE) have emerged as efficient cell labeling reagents, where positive outcomes were observed in long-term cancer cell tracing in vivo. In the current study, we designed, synthesized, and analyzed the biocompatibility of AIE-NPs in cultured neurons such as in mouse neuronal progenitor cells (NPCs) and hESC-derived neurons. Our data demonstrated that AIE-NPs show high degree of penetration into cells and presented intracellular long-term retention in vitro without altering the neuronal proliferation, differentiation, and viability. Furthermore, we have tracked AIE-NPs labeled neuronal grafts in mouse brain striatum in various time points post-transplantation. We demonstrated prolonged cellular retention of AIE-NPs labeled neuronal grafts 1 month post-transplantation in mouse brain striatum. Lastly, we have shown activation of brain microglia in response to AIE-NPs labeled grafts. Together, these findings highlight the potential application of AIE-NPs in neuronal transplantation.

A microfiber scaffold-based 3D in vitro human neuronal culture model of Alzheimer's disease.

Increasing evidence indicates superiority of three-dimensional (3D) in vitro cell culture systems over conventional two-dimensional (2D) monolayer cultures in mimicking native in vivo microenvironments. Tissue-engineered 3D culture models combined with stem cell technologies have advanced Alzheimer's disease (AD) pathogenesis studies. However, existing 3D neuronal models of AD overexpress mutant genes or have heterogeneities in composition, biological properties and cell differentiation stages. Here, we encapsulate patient induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPC) in poly(lactic-co-glycolic acid) (PLGA) microtopographic scaffolds fabricated via wet electrospinning to develop a novel 3D culture model of AD. First, we enhanced cellular infiltration and distribution inside the scaffold by optimizing various process parameters such as fiber diameter, pore size, porosity and hydrophilicity. Next, we compared key neural stem cell features including viability, proliferation and differentiation in 3D culture with 2D monolayer controls. The 3D microfibrous substrate reduces cell proliferation and significantly accelerates neuronal differentiation within seven days of culture. Furthermore, 3D culture spontaneously enhanced pathogenic amyloid-beta 42 (Aß42) and phospho-tau levels in differentiated neurons carrying familial AD (FAD) mutations, compared with age-matched healthy controls. Overall, our tunable scaffold-based 3D neuronal culture platform serves as a suitable in vitro model that robustly recapitulates and accelerates the pathogenic characteristics of FAD-iPSC derived neurons.