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In Vivo Osteo-organoid Approach for Harvesting Therapeutic Hematopoietic Stem/Progenitor Cells
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Prostaglandin E2 Enhances Aged Hematopoietic Stem Cell Function.

Andrea M Patterson1, P Artur Plett2, Carol H Sampson2

  • 1Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, 980 West Walnut St, Indianapolis, IN, 46202, USA. anmapatt@iu.edu.

Stem Cell Reviews and Reports
|May 11, 2021
PubMed
Summary
This summary is machine-generated.

16,16-dimethyl prostaglandin E2 (dmPGE2) enhances aged hematopoietic stem cell (HSC) function and transplantation success. This finding offers new therapeutic potential for elderly HSC transplantation by improving aged HSC engraftment.

Keywords:
AgingHematopoietic stem cellsMouse modelProstaglandin E2RNA sequencingTransplantation

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Area of Science:

  • Hematology
  • Immunology
  • Gerontology

Background:

  • Aging hematopoietic stem cells (HSCs) exhibit functional decline and myeloid bias, impacting transplantation outcomes.
  • Donor age is a critical factor in HSC transplantation success, yet methods to improve aged HSC function are lacking.
  • The molecular response of aged HSCs to stimuli like 16,16-dimethyl prostaglandin E2 (dmPGE2) remains largely unknown.

Purpose of the Study:

  • To investigate the effect of dmPGE2 on the function and transplantation potential of aged HSCs.
  • To compare the molecular responses of young and aged HSCs to dmPGE2.
  • To identify key mediators of dmPGE2-induced HSC enhancement and age-related signaling.

Main Methods:

  • Ex vivo pulse of bone marrow cells from young and aged mice with dmPGE2.
  • Serial competitive transplantation assays to assess long-term repopulation capacity.
  • RNA sequencing of phenotypically-isolated HSCs to analyze molecular responses.

Main Results:

  • dmPGE2 significantly enhanced long-term repopulation from aged HSC grafts, comparable to young grafts.
  • Molecular responses to dmPGE2 in HSCs were similar in young and aged mice, involving CREB1 activation and enhanced cell survival.
  • HSC expression of the PGE2 receptor EP4 increased with age, suggesting its role in HSC function.

Conclusions:

  • Aging does not fundamentally alter the major dmPGE2 response pathways that enhance HSC function.
  • dmPGE2 effectively improves both young and aged HSC function and transplantation outcomes.
  • These findings have significant implications for expanding the therapeutic use of HSCs from elderly donors.