# HIV, Methamphetamine and Human iPSC-derived Microglia-containing Cerebral Organoids

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $617,622

## Abstract

Abstract
Methamphetamine (METH), a potent addictive psychostimulant, is one of the most commonly abused drugs in
the United States. METH abuse is highly prevalent in HIV-infected individuals, which presents unique
challenges for HIV prevention and treatment. Given the overlap impact of METH use and HIV on neuronal
damage in the central nervous system (CNS), it becomes urgent to understand the role of interplays between
METH and HIV in the pathogenesis of HIV-associated neurocognitive disorders (HAND). However, studies of
HAND have been hampered by difficulties in collecting live brain cells from autopsy or biopsy of HIV patients.
Recent success in generating microglia and cerebral organoids from human induced pluripotent stem cells
(iPSCs) now offers a great opportunity to investigate the impact of METH and/or HIV on the CNS. The overall
objective of this project is to validate and establish a clinically relevant in vitro brain model for
NeuroAIDS research in the context of drug abuse. The project will be carried out by two P.I.s who have the
complementary expertise and experience in the proposed studies. Dr. Ho has been working on the impact of
abused drugs (METH and opioids) on peripheral/CNS innate immunity and HIV infection of
macrophages/microglia since 1999. Dr. Hu’s research focuses on neurogenesis, iPSC generation,
inflammasomes, CRISPR/Cas HIV eradication and HAND. Their recent collaborative work has successfully
generated and characterized the human iPSC-derived microglia-containing cerebral organoids (MCOs) which
express the major CNS cell types: neural stem/progenitor cells, neurons, astrocytes, and microglia. More
importantly, these MCOs could be infected by HIV. Based on these important findings, we propose three
specific aims: Aim 1. To study dynamic HIV infection of human iPSC-derived MCOs and the impact of METH
on HIV infection of MCOs; Aim 2. To determine HIV-infected cell types and the primary target/reservoir cells of
HIV in MCOs; Aim 3. To study the impact of HIV infection on the development and neuronal circuitry in MCOs.
Successful completion of this project should provide an in vitro brain model to study the roles of HIV infection
and drugs of abuse in the pathogenesis of NeuroAIDS.

## Key facts

- **NIH application ID:** 10055449
- **Project number:** 1R01DA051893-01
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** WENZHE HO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $617,622
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055449

## Citation

> US National Institutes of Health, RePORTER application 10055449, HIV, Methamphetamine and Human iPSC-derived Microglia-containing Cerebral Organoids (1R01DA051893-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10055449. Licensed CC0.

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