Tempo-iMG™, Tempo-iCort™, Tempo-iDopaNer™, and Tempo-iMotorNer™ were utilized in a study cited in plos.org that examined the cross-talking relationship between microglia and neurons. It was critical that the researchers deployed Tempo’s iPSC-derivative cell types to establish a human relevant model to study HIV infection.
Citation Summary:
Scientists from Case Western Reserve University investigated the triggers of neurological degeneration in patients with HIV-associated neurocognitive disorders (HAND). Microglia form the first response to HIV infection within the CNS, and have been suggested to compound HIV damage to neurons through the release of cytokines and toxins. In studying this relationship, researchers utilized a co-culture system in order to understand the interactions between neurons and microglia. In doing so, they found that healthy neurons induced HIV silencing in microglia. By contrast, damaged neurons increased HIV viral expression within microglia.
How do neurons impact microglial infection and latency?
Researchers utilized Tempo-iCort™, Tempo-iDopaNer™, and Tempo-iMotorNer™ to demonstrate that neurons are capable of silencing HIV. While they found that HIV expression was not significantly inhibited by motor neurons (iMotorNer™), iCort™ and iDopaNer™neurons triggered significant reduction in HIV expression. In utilizing these differentiated mature neuronal cell types from human iPSCs, researchers were able to effectively model neuronal silencing. Additionally, researchers found that the iPSC-derived neurons could induce HIV latency in infected microglia. By comparing neurons with HIV expression in primary microglia and Tempo-iMG™ cells, researchers demonstrated that Tempo-iMG™ cells were functionally equivalent to human primary microglia.
How do HIV-infected microglia impact neurons?
As for microglial cell’s ability to affect neurons, researchers found that HIV infected microglial cells induced neuronal damage. In co-culturing neurons with both uninfected and infected microglia, researchers found that there was a reduction in intact dendrites in neurons that had been exposed to infected microglia.
Why are these results significant?
These results are significant because researchers were able to show that neuronal and microglial crosstalk plays a key role in regulating HIV latency. These discoveries suggested that anti-inflammatory therapeutics may be key to controlling HIV and should be further investigated as potential therapeutics. Tempo’s products offered the researchers a human relevant model that reduced variabilities observed when using primary cell sources (“mixed sources”). And, human iPSC-derived cell types served as an alternative to the traditional highly-engineered artificially immortalized cell lines.
Where do Tempo products fit in?
In this study, researchers needed to effectively model the CNS interactions between neurons and microglia. While animal studies have been typically conducted as a next-best precursor to human trials, their overall costs and lack of congruency to actual human physiology and pathophysiology showed that alternatives to animal models must be utilized in research and drug development. Additionally, mouse models for HIV are uniquely costly in terms of environmental impact, safety practices, and are not exact models of HIV expression in humans. By contrast, using human iPSC-derived cells infected with HIV could reduce environmental impact, ensure researcher safety, and provide accurate human models for scientific investigations.
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Allison Kennedy
