A groundbreaking study has uncovered a special stem cell that can reduce the amount of virus causing AIDS and boost the body’s antiviral immunity – repairing damage to the gut caused by the condition.
The study, led by UC Davis researchers, has discovered the stem cell which they say repairs and restores the gut’s lymphoid follicles damaged by the simian immunodeficiency virus (SIV), the equivalent of the human immunodeficiency virus (HIV) in non-human primates.
It demonstrated the mechanism through which mesenchymal stem/stromal cells (MSCs) enhance the body’s immune response to the virus and provides a roadmap for developing multi-pronged HIV eradication strategies.
The findings have been published in JCI Insight.
Repairing the immune system
Lymphoid tissue that is found in the gut is an early site for viral replication and the establishment of viral reservoirs.
Satya Dandekar, senior author of this paper and professor at and the chairperson of the Department of Medical Microbiology and Immunology at UC Davis and affiliated with the California National Primate Research Center, said: “Impaired immune functions in HIV infection and incomplete immune recovery pose obstacles for eradicating HIV. Our objective was to develop strategies to boost immunity against the virus and empower the host immune system to eradicate the virus. We sought to repair, regenerate, and restore the lymphoid follicles that are damaged by the viral infection.”
The group has previously shown that an HIV infection causes severe loss of gut mucosal T immune cells and disrupts the gut epithelial barrier lining, leading to a leaky gut.
“The lymphoid follicles are organised structures where the long-term immune attack is launched against pathogens by generating antibody response targeting the virus. These important regions are functionally impaired very early following HIV infection,” Dandekar said.
Antiretroviral drugs effectively suppress viral replication, however, they are not able to repair the damage to the immune system caused by the virus and cannot restore the functionality of the lymphoid follicles on their own.
Using stem cells to repair damage
To find out if stem cells can help to repair damage, the researchers administered bone marrow-derived MSC in a rhesus macaque model of AIDS that had impaired immunity and disrupted gut functions due to the viral infection.
Dandekar said: “We are starting to recognise the great potential of these stem cells in the context of infectious diseases. We have yet to discover how these stem cells can impact chronic viral infections such as AIDS.”
The findings demonstrated that the MSCs can modulate, alter, and remodel the damaged mucosal site with immediate benefits including a rapid rise in antibodies and T-immune cells targeting the virus.
The team highlight that the stem cells were instrumental in the recovery and restoration of these lymphoid follicles.
An innovative, multi-pronged HIV cure strategy
MSCs were able to increase the host’s antiviral response by repairing the lymphoid follicles, restoring the mucosal immunity, and reviving what has been targeted by the virus very early on.
Dandekar said: “Stem cells are good synergistic partner components with drugs. The antiretroviral drugs can stop the fire of the viral infection but cannot restore the forest of the lymphoid tissue compartment. The MSCs would rejuvenate the field and bring back immune vitality.”
MSC treatments require well defined cell quality controls and specific delivery mechanisms. The UC Davis Stem Cell Program is leading multiple clinical trials on MSC use in treating diseases such as spina bifida and Huntington’s disease.
