Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection

Nazari-Shafti, Timo Z.; Freisinger, Eva; Roy, Upal; Bulot, Christine; Senst, Christiane; Dupin, Charles; Chaffin, Abigail E.; Srivastava, Sudesh K; Mondal, Debasis; Alt, Eckhard; Izadpanah, Reza

doi:10.1186/1742-4690-8-3

Cited by 25 publications

(24 citation statements)

References 50 publications

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“…Transcriptome analysis of human BMMSCs and AD-MSCs cultured in this medium displayed transcriptional profiles comparable to those using the traditional culture media(Chase et al, 2012). AD-MSCs derived hematopoietic cells acquired cell surface human immunodeficiency virus-receptor and coreceptors during differentiation in vitro and became permissive to viral infection whereas undifferentiated AD-MSCs did not show productive infection(Nazari-Shafti et al, 2011).…”

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confidence: 84%

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Kasoju

Wang

Zhang

et al. 2017

Biotechnology Advances

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The plastic-adherent, fibroblast-like, clonogenic cells found in the human body now defined as multipotent "Mesenchymal Stromal Cells" (MSCs) hold immense potential for cell-based therapies. Recently, research and basic knowledge of these cells has fast-tracked, both from fundamental and translational perspectives. There have been important discoveries with respect to the available variety of tissue sources, the development of protocols for their easy isolation and in vitro expansion and for directed differentiation into various cell types. In addition, there has been discovery of novel abilities such as immune-modulation and further development of the use of biomaterials to aid isolation, expansion and differentiation together with improved delivery to the selected optimal tissue site. However, the molecular fingerprint of MSCs in these contexts remains imprecise and inadequate. Consequently, without this crucial knowledge it is difficult to achieve progress to determine with precision their practical developmental potentials. Detailed investigations on the global gene expression, or transcriptome, of MSCs could offer essential clues in this regard. In this article, we address the challenges associated with MSC transcriptome studies, the paradoxes observed in published experimental results and the need for careful transcriptomic analysis. We describe the exemplary applications with various transcriptome platforms that are used to address the variation in biomarkers and the identification of differentiation processes. The evolution and the potentials for adapting next-generation sequencing (NGS) technology in transcriptome analysis are discussed. Lastly, based on review of the existing understanding and published studies, we propose how NGS may be applied to promote further understanding of the biology of MSCs and their use in allied fields such as regenerative medicine.

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confidence: 84%

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Kasoju

Wang

Zhang

et al. 2017

Biotechnology Advances

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“…Additionally, by contrast to bone marrow hematopoietic stem cells which can be infected with HIV, mesenchymal stem cells derived from human adipose tissue do not support productive HIV infection, although they can be productively infected if differentiated into hematopoietic cells [42]. Thus, CD4 T cells and macrophages are likely to be the only cells infected with HIV in adipose tissue.…”

Section: Establishment Of Hiv Reservoirs In Adipose Tissue and Viral mentioning

confidence: 99%

HIV Persistence in Adipose Tissue Reservoirs

Couturier

Lewis

2018

Curr HIV/AIDS Rep

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Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and selective distribution of antiretroviral drugs, the sequestration of infected immune cells within fat depots likely represents a major challenge for cure efforts.

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“…Acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (HIV), poses a real threat to human life [80]. Despite the advent of highly active antiretroviral therapy (HAART) that suppresses plasma viral load but does not cure disease, HIV-1 persists in latent tissue reservoirs, mainly in macrophages and T-helper lymphocytes, and this poses significant challenge to long-term cure [2,[80][81][82]. HIV-1 predominantly infects HSCs such as macrophages, monocytes, and T-helper lymphocytes [82].…”

Section: Mscs In Hiv Infection and Aidsmentioning

confidence: 99%

“…Despite the advent of highly active antiretroviral therapy (HAART) that suppresses plasma viral load but does not cure disease, HIV-1 persists in latent tissue reservoirs, mainly in macrophages and T-helper lymphocytes, and this poses significant challenge to long-term cure [2,[80][81][82]. HIV-1 predominantly infects HSCs such as macrophages, monocytes, and T-helper lymphocytes [82]. Non-immune responders (NIRs) do respond to HAART, which effectively suppresses HIV replication, but do not show any improvement in their immune status as reflected by an increase in CD4+ T-cell counts [83].…”

Section: Mscs In Hiv Infection and Aidsmentioning

confidence: 99%

“…Coexposure to MSC-conditioned media can enhance the latency-reactivation efficacy of the approved latency reversing drugs vorinostat and panobinostat [81]. Undifferentiated AT resident MSCs are not permissive to HIV-1 infection despite that HIV-1 exposure may increase the expression of some hematopoietic lineage related genes [82]. It has been reported that transfusions of UCB-MSC or more specifically WJ are well tolerated and can efficiently improve immune reconstitution in HIV-infected individuals who are NIRs [83,84].…”

Section: Mscs In Hiv Infection and Aidsmentioning

confidence: 99%

See 1 more Smart Citation

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

Al-Anazi¹,

Al-Anazi²,

Al-Jasser³

2020

Update on Mesenchymal and Induced Pluripotent Stem Cells

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Mesenchymal stem cells are heterogenous adult multipotent stromal cells that can be isolated from various sources including: bone marrow, peripheral blood, umbilical cord blood, dental pulp, and adipose tissue. They have certain immunomodulatory, immunosuppressive, and antimicrobial properties that enable them to have several therapeutic and clinical applications including: treatment of autoimmune disorders, role in hematopoietic stem cell transplantation and regenerative medicine, as well as treatment of various infections and their associated complications such as septic shock and acute respiratory distress syndrome. Although more success has been achieved in preclinical trials on the use of mesenchymal stem cells in animal models than in human clinical trials, particularly in septic shock and Chagas disease, more progress has been made in both disorders after the recent use of specific sources and certain doses of mesenchymal stem cells. Nevertheless, the utilization of this type of stem cells has shown remarkable progress in the treatment of few infections such as tuberculosis. The clinical application of mesenchymal stem cells in the treatment of several diseases still faces real challenges that need to be resolved. The following book chapter will be an updated review on the role of mesenchymal stem cells in various infections and their complications.

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Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection

Cited by 25 publications

References 50 publications

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

HIV Persistence in Adipose Tissue Reservoirs

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

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