HMN 2026: How Human stem cell lines offer new resource to help study HIV progression

King’s College London researchers have created a unique collection of human stem cell models that could help to uncover why HIV leads to different outcomes in different people. The research was carried out by Dr. Nathalia Almedia, postdoctoral researcher, and Sam Acors, former Ph.D. student, who are co-lead authors of the paper published in Stem Cell Reports.

Building a lasting stem cell resource

They generated a cell bank of a special type of stem cell (called induced pluripotent stem cells or iPSCs) from 18 people living with HIV, creating a long-lasting research resource that can be used to model HIV infection in the laboratory. The 50 iPSC lines were derived from participants in the Multicenter AIDS Cohort Study (MACS), representing a wide range of disease trajectories.

People living with HIV experience the disease in markedly different ways. While some individuals develop severe illness quickly, others remain healthy for many years. These differences cannot be fully explained by the virus or environment alone, as host genetics play a significant role in shaping disease progression.

Studying these genetic factors using patient samples has traditionally been limited by the availability and lifespan of blood cells. Once used, such samples cannot be replaced, and research is restricted to the cell types present in blood.

To overcome these challenges, researchers reprogrammed blood cells from the participants into iPSCs. iPSCs can be grown indefinitely in the lab and can be programmed to develop into almost any cell type in the body.

Turning stem cells into HIV target cells

The researchers converted the stem cells into macrophages—immune cells that play a key role in HIV infection. They then exposed these lab-grown macrophages to HIV and showed that the virus could enter the cells and replicate. This demonstrated that the iPSC-derived cells function like genuine HIV target cells and can be used to model HIV infection and host responses in the laboratory.

“This research dramatically expands what we can do with a frozen blood sample, turning it into a powerful research platform. By creating these stem cell lines, we now have a permanent resource that can be shared openly with researchers worldwide,” says Dr. Almeida.

A versatile platform for future studies

The creation of this iPSC bank transforms finite patient samples into a permanent research platform. The 50 cell lines could be used to generate immune cells, lung cells, gut cells, and complex three-dimensional structures known as organoids, which mimic key features of human organs in the laboratory.

“This has been a long journey for us, and I am particularly pleased for Nathalia Almeida and Sam Acors, whose dedication and attention to detail enabled the creation of this panel of lines. It will be fascinating to see what we and others can discover about HIV biology and pathogenesis in the years to come. We are indebted to our long-term collaborator, Professor Steven Wolinsky, and his team at Northwestern University for providing the clinical specimens, without which this work would not have been possible,” says Professor Mike Malim, co-senior author of the paper.

Linking donor genetics to HIV outcomes

Because each iPSC line retains the full genetic information of the individual it was derived from, the cell lines offer a way of directly examining how genetic differences influence HIV infection and immune responses across diverse patient groups.

The iPSC collection is particularly valuable because of the unique history of the donors. The samples originate from individuals who experienced different phases of the HIV epidemic, including its peak in the 1980s and 1990s, and who had widely varying clinical outcomes despite exposure to the same virus.

The resource could also enable investigation of one of the central challenges in HIV research, which is understanding why some people progress rapidly to AIDS, while others naturally control the virus for many years.

Next questions for HIV and beyond

“These iPSCs retain the unique genetic context of patients and allow infection, latency, and host–virus interactions to be modeled in human cell types that are otherwise inaccessible, such as microglia. Their future use in complex organoids systems will enable investigation on cell–cell transmission dynamics, persistence, immune cross-talk, and others, in a controlled yet physiologically relevant context, and we look forward to sharing this resource with the scientific community,” says Dr. Luis Apolonia, co-senior author of the paper.

The researchers emphasize that this work represents an important first step for modeling HIV infection in the lab. A key next stage will be determining how closely experiments in the cell lines reflect what occurs in the human body, which is far more complex than cells grown in isolation.

Future studies will explore whether cells derived from those who do not progress rapidly to AIDS show different patterns of HIV infection compared to those who do progress rapidly. Beyond HIV, the iPSC lines could also be used to study other infections that disproportionately affect people with compromised immune systems, including tuberculosis, hepatitis, and salmonella.

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