Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release Article Swipe
Steven J. Greco
,
Seda Ayer
,
Khadidiatou Guiro
,
Garima Sinha
,
Robert Donnelly
,
Markos H. El-Far
,
Lauren S. Sherman
,
Yannick Kenfack
,
Sri Harika Pamarthi
,
Marina Gergues
,
Oleta A. Sandiford
,
Michael Schonning
,
Jean‐Pierre Etchegaray
,
Pranela Rameshwar
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.18632/aging.203689
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.18632/aging.203689
This study addresses the potential to reverse age-associated morbidity by establishing methods to restore the aged hematopoietic system. Parabiotic animal models indicated that young secretome could restore aged tissues, leading us to establish a heterochronic transwell system with aged mobilized peripheral blood (MPB), co-cultured with young MPB or umbilical cord blood (UCB) cells. Functional studies and omics approaches indicate that the miRNA cargo of microvesicles (MVs) restores the aged hematopoietic system. The in vitro findings were validated in immune deficient (NSG) mice carrying an aged hematopoietic system, improving aged hallmarks such as increased lymphoid:myeloid ratio, decreased inflammation and cellular senescence. Elevated MYC and E2F pathways, and decreased p53 were key to hematopoietic restoration. These processes require four restorative miRs that target the genes for transcription/differentiation, namely PAX and phosphatase PPMIF. These miRs when introduced in aged cells were sufficient to restore the aged hematopoietic system in NSG mice. The aged MPBs were the drivers of their own restoration, as evidenced by the changes from distinct baseline miR profiles in MPBs and UCB to comparable expressions after exposure to aged MPBs. Restorative natural killer cells eliminated dormant breast cancer cells in vivo, indicating the broad relevance of this cellular paradigm - preventing and reversing age-associated disorders such as clearance of early malignancies and enhanced responses to vaccine and infection.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.18632/aging.203689
- https://www.aging-us.com/article/203689/pdf
- OA Status
- hybrid
- Cited By
- 10
- References
- 71
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3212719552
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3212719552Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.18632/aging.203689Digital Object Identifier
- Title
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Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles releaseWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-11-11Full publication date if available
- Authors
-
Steven J. Greco, Seda Ayer, Khadidiatou Guiro, Garima Sinha, Robert Donnelly, Markos H. El-Far, Lauren S. Sherman, Yannick Kenfack, Sri Harika Pamarthi, Marina Gergues, Oleta A. Sandiford, Michael Schonning, Jean‐Pierre Etchegaray, Pranela RameshwarList of authors in order
- Landing page
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https://doi.org/10.18632/aging.203689Publisher landing page
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https://www.aging-us.com/article/203689/pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://www.aging-us.com/article/203689/pdfDirect OA link when available
- Concepts
-
Haematopoiesis, Microvesicles, Biology, Immune system, Immunology, Stem cell, microRNA, Inflammation, Myeloid, Cancer research, Cell biology, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
10Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 5, 2023: 4, 2022: 1Per-year citation counts (last 5 years)
- References (count)
-
71Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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