Person:

Zhang, Qi

Stem cell technology has facilitated the development of human cell culture models of disease that can be used to study pathogenesis and test therapeutic candidates. These models hold particular promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the design and characterization of a novel three-dimensional (3D) culture system that exhibits key events in the pathogenic cascade of AD, including extracellular aggregation of amyloid β peptides and accumulation of hyperphosphorylated/aggregated tau protein. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD (FAD) mutations, the differentiation of the hNPCs in a 3D Matrigel matrix, and the analysis of AD pathologenesis in this model. The same principles may be applicable to models of other inherited neurodegenerative diseases characterized by the aberrant aggregation of misfolded proteins.

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.