Cargando…
Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release
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 pe...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610119/ https://www.ncbi.nlm.nih.gov/pubmed/34762598 http://dx.doi.org/10.18632/aging.203689 |
_version_ | 1784603042301083648 |
---|---|
author | Greco, Steven J. Ayer, Seda Guiro, Khadidiatou Sinha, Garima Donnelly, Robert J. El-Far, Markos H. Sherman, Lauren S. Kenfack, Yannick Pamarthi, Sri Harika Gergues, Marina Sandiford, Oleta A. Schonning, Michael J. Etchegaray, Jean-Pierre Rameshwar, Pranela |
author_facet | Greco, Steven J. Ayer, Seda Guiro, Khadidiatou Sinha, Garima Donnelly, Robert J. El-Far, Markos H. Sherman, Lauren S. Kenfack, Yannick Pamarthi, Sri Harika Gergues, Marina Sandiford, Oleta A. Schonning, Michael J. Etchegaray, Jean-Pierre Rameshwar, Pranela |
author_sort | Greco, Steven J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8610119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-86101192021-11-24 Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release Greco, Steven J. Ayer, Seda Guiro, Khadidiatou Sinha, Garima Donnelly, Robert J. El-Far, Markos H. Sherman, Lauren S. Kenfack, Yannick Pamarthi, Sri Harika Gergues, Marina Sandiford, Oleta A. Schonning, Michael J. Etchegaray, Jean-Pierre Rameshwar, Pranela Aging (Albany NY) Research Paper 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. Impact Journals 2021-11-11 /pmc/articles/PMC8610119/ /pubmed/34762598 http://dx.doi.org/10.18632/aging.203689 Text en Copyright: © 2021 Greco et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Greco, Steven J. Ayer, Seda Guiro, Khadidiatou Sinha, Garima Donnelly, Robert J. El-Far, Markos H. Sherman, Lauren S. Kenfack, Yannick Pamarthi, Sri Harika Gergues, Marina Sandiford, Oleta A. Schonning, Michael J. Etchegaray, Jean-Pierre Rameshwar, Pranela Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release |
title | Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release |
title_full | Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release |
title_fullStr | Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release |
title_full_unstemmed | Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release |
title_short | Restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release |
title_sort | restoration of aged hematopoietic cells by their young counterparts through instructive microvesicles release |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610119/ https://www.ncbi.nlm.nih.gov/pubmed/34762598 http://dx.doi.org/10.18632/aging.203689 |
work_keys_str_mv | AT grecostevenj restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT ayerseda restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT guirokhadidiatou restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT sinhagarima restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT donnellyrobertj restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT elfarmarkosh restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT shermanlaurens restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT kenfackyannick restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT pamarthisriharika restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT gerguesmarina restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT sandifordoletaa restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT schonningmichaelj restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT etchegarayjeanpierre restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease AT rameshwarpranela restorationofagedhematopoieticcellsbytheiryoungcounterpartsthroughinstructivemicrovesiclesrelease |