In groundbreaking study, a team of UC Davis researchers discovered a special type of stem cell that can reduce the amount of the virus that causes AIDS, boost the body’s antiviral immunity, and repair and restore lymphoid follicles gut damaged by simian immunodeficiency virus (SIV), the equivalent of human immunodeficiency virus (HIV) in non-human primates.
The study, published on June 22 in JCI Overview, showed the mechanism by which mesenchymal stem / stromal cells (MSCs) enhance the body’s immune response to the virus. It also provides a roadmap for developing multi-pronged HIV eradication strategies.
“Impaired immune functions in HIV infection and incomplete immune recovery are obstacles to eradication of HIV,” said Satya Dandekar, lead author of this article. “Our goal was to develop strategies to enhance immunity against the virus and allow the host’s immune system to eradicate the virus. We sought to repair, regenerate and restore lymphoid follicles damaged by viral infection. “
Lymphoid tissue in the intestine is an early site for viral replication and the establishment of viral reservoirs. Dandekar’s group has previously shown that HIV infection causes severe loss of immune cells in the intestinal lining and disrupts the wall of the intestinal epithelial barrier, leading to intestinal leakage.
“Lymphoid follicles are organized structures where the long-term immune attack is launched against pathogens by generating an antibody response targeting the virus. These important regions are functionally altered very soon after infection with HIV,” said Dandekar.
Although antiretroviral drugs effectively suppress viral replication, they do not repair the damage the virus causes to the immune system. On their own, these drugs cannot restore the functionality of lymphoid follicles damaged by HIV infection.
Can stem cells fight intestinal damage caused by HIV?
The researchers administered MSC derived from the bone marrow into a rhesus macaque model of AIDS that exhibited impaired immunity and disrupted bowel functions due to the viral infection.
“We are starting to recognize the great potential of these stem cells in the context of infectious diseases. We have yet to find out how these stem cells can impact chronic viral infections such as AIDS,” said Dandekar. She is Professor and Chair of the Department of Medical Microbiology and Immunology at UC Davis and affiliated with the California National Primate Research Center.
The study found that MSCs can modulate, alter, and reshape the damaged mucosal site. The benefits were immediate, with a rapid rise in antibodies and immune T cells targeting the virus. Stem cells have been instrumental in the recovery and restoration of these lymphoid follicles.
MSCs also provide an opportunity for an innovative multi-pronged HIV cure strategy by complementing current HIV treatments.
“Stem cells are good synergistic partner components with drugs. Antiretroviral drugs can stop the fire of viral infection but cannot restore the forest of the lymphoid tissue compartment. MSCs would rejuvenate the field and restore immune vitality.” , said Dandekar.
Even without the use of antiviral drugs, MSCs were able to increase the host’s antiviral response by repairing lymphoid follicles, restoring mucosal immunity, and reviving what was targeted by the virus early on.
MSC treatments require well-defined cell quality controls and specific delivery mechanisms. The Stem Cell Program at UC Davis, a center of excellence for stem cell research, is conducting several clinical trials on the use of MSCs in the treatment of diseases such as spina bifida and Huntington’s disease. The results of this study provide a scientific basis for investigating MSC in the treatment of HIV and other infectious diseases in clinical settings.
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