Hiv Stem Cell Therapy On The Horizon By Regenerating Damaged Cells In The Gut

Researchers discover the role of stem cells in gut lymphoid tissue regeneration and enhanced immunity against SIV in non-human primate studies, generating new avenues in HIV eradication strategies using stem cell therapy.

Researchers from the &University of California Davis &(CA, USA) have identified new mesenchymal stem/stromal cell (MSC) functions in the restoration of gut lymphoid follicles in animals infected with simian immunodeficiency virus (SIV). SIV is equivalent to human immunodeficiency virus (HIV) in non-human primates and provides an AIDS model to study this new anti-HIV stem cell therapy in the laboratory.

Uncovering the role of stem cells’ ability to suppress HIV infection and provide immune protection against the virus could be a milestone in developing a cure for AIDS, a disease that continues to burden the lives of many individuals across the world. Current antiretroviral therapy (ART) fails to eliminate hidden HIV pockets called ‘reservoirs’ in lymphoid tissues and this new research may be the key to targeted HIV eradication in these reservoirs.

This study, published in &JCI Insight, demonstrated the molecular and metabolic mechanisms through which MSCs in the gut increase antiviral response pathways to suppress HIV infection and generate host immunity. HIV disease progression to AIDs is characterized by loss of CD4+ T cells and immune dysfunction. The researchers investigated MSCs in the gut due to the occurrence of HIV reservoirs in gut-associated lymphoid tissue (GALT) where HIV depletes CD4+ T cells early in infection.

“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,” explained Satya Dandekar, senior author. The focus on gut lymphoid tissue in this paper was propelled by Dandekar’s group’s previous research demonstrating that &SIV causes immune disruption in gut epithelial cells.

Dandekar added: “The lymphoid follicles are organized 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.”

The group discovered that infusing the SIV-infected rhesus macaque AIDS model with MSCs derived from healthy bone marrow restored damaged GALT to regenerate mucosal antiviral immunity. By restoring critical follicular B and T cells in the gut, the MSC treatment enhanced antibody levels and immunity against SIV by increasing viral antigen presentation.

This study particularly delved into the ‘transcri ptional signature’ of the gut mucosal cells in the MSC-treated animals to investigate the effects of this treatment. The signature indicated an increased expression of immune-related genes, such as MAMU-DPA, (encoding MHC Class II antigen presenting protein) which warrants future investigation.

Dandekar’s group’s findings are very promising for the field of stem cell therapy in the context of infectious diseases. “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,” Dandekar commented.

MSCs hold great potential in creating a multi-pronged approach to the fight against HIV by assisting current HIV treatments and enhancing therapy strategies to hopefully provide a cure.

Source: lt;/strong>Weber MG, Walters-Laird CJ, Kol A &et al. &Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection. &JCI Insight. 6(12), e149033 (2021)& &https://health.ucdavis.edu/health-news/contenthub/research-provides-a-roadmap-to-hiv-eradication-via-stem-cell-therapy-/2021/06