Retroviral infection of human neurospheres and use of stem Cell EVs to repair cellular damage.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 02 2022
07 02 2022
Historique:
received:
24
07
2020
accepted:
05
01
2022
entrez:
8
2
2022
pubmed:
9
2
2022
medline:
11
3
2022
Statut:
epublish
Résumé
HIV-1 remains an incurable infection that is associated with substantial economic and epidemiologic impacts. HIV-associated neurocognitive disorders (HAND) are commonly linked with HIV-1 infection; despite the development of combination antiretroviral therapy (cART), HAND is still reported to affect at least 50% of HIV-1 infected individuals. It is believed that the over-amplification of inflammatory pathways, along with release of toxic viral proteins from infected cells, are primarily responsible for the neurological damage that is observed in HAND; however, the underlying mechanisms are not well-defined. Therefore, there is an unmet need to develop more physiologically relevant and reliable platforms for studying these pathologies. In recent years, neurospheres derived from induced pluripotent stem cells (iPSCs) have been utilized to model the effects of different neurotropic viruses. Here, we report the generation of neurospheres from iPSC-derived neural progenitor cells (NPCs) and we show that these cultures are permissive to retroviral (e.g. HIV-1, HTLV-1) replication. In addition, we also examine the potential effects of stem cell derived extracellular vesicles (EVs) on HIV-1 damaged cells as there is abundant literature supporting the reparative and regenerative properties of stem cell EVs in the context of various CNS pathologies. Consistent with the literature, our data suggests that stem cell EVs may modulate neuroprotective and anti-inflammatory properties in damaged cells. Collectively, this study demonstrates the feasibility of NPC-derived neurospheres for modeling HIV-1 infection and, subsequently, highlights the potential of stem cell EVs for rescuing cellular damage induced by HIV-1 infection.
Identifiants
pubmed: 35132117
doi: 10.1038/s41598-022-05848-x
pii: 10.1038/s41598-022-05848-x
pmc: PMC8821538
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2019Subventions
Organisme : NCI NIH HHS
ID : R33 CA206937
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI074410
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI078859
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA050176
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI043894
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR068436
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI127351
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099029
Pays : United States
Informations de copyright
© 2022. The Author(s).
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