Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Mesenchymal stromal cells lower platelet activation and assist in platelet formation in vitro
Avital Mendelson, … , Xiuli An, Karina Yazdanbakhsh
Avital Mendelson, … , Xiuli An, Karina Yazdanbakhsh
Published August 22, 2019
Citation Information: JCI Insight. 2019;4(16):e126982. https://doi.org/10.1172/jci.insight.126982.
View: Text | PDF
Research Article Hematology Stem cells

Mesenchymal stromal cells lower platelet activation and assist in platelet formation in vitro

  • Text
  • PDF
Abstract

The complex process of platelet formation originates with the hematopoietic stem cell, which differentiates through the myeloid lineage, matures, and releases proplatelets into the BM sinusoids. How formed platelets maintain a low basal activation state in the circulation remains unknown. We identify Lepr+ stromal cells lining the BM sinusoids as important contributors to sustaining low platelet activation. Ablation of murine Lepr+ cells led to a decreased number of platelets in the circulation with an increased activation state. We developed a potentially novel culture system for supporting platelet formation in vitro using a unique population of CD51+PDGFRα+ perivascular cells, derived from human umbilical cord tissue, which display numerous mesenchymal stem cell (MSC) properties. Megakaryocytes cocultured with MSCs had altered LAT and Rap1b gene expression, yielding platelets that are functional with low basal activation levels, a critical consideration for developing a transfusion product. Identification of a regulatory cell that maintains low baseline platelet activation during thrombopoiesis opens up new avenues for improving blood product production ex vivo.

Authors

Avital Mendelson, Ana Nicolle Strat, Weili Bao, Peter Rosston, Georgia Fallon, Sophie Ohrn, Hui Zhong, Cheryl Lobo, Xiuli An, Karina Yazdanbakhsh

×

Figure 1

Lepr+ stromal cells in the mouse BM help to maintain normal platelet numbers in the circulation and assist in lowering their basal activation levels.

Options: View larger image (or click on image) Download as PowerPoint
Lepr+ stromal cells in the mouse BM help to maintain normal platelet num...
Triple transgenic Lepr+tdTomato+DTA+ mice were generated. The efficiency of Lepr+ cell depletion was evaluated by (A) quantifying the remaining Lepr+ cells in the BM (n = 3–4). (B) We did not observe any significant difference in the number of megakaryocytes present in the femur of the DTA group compared with the control group (n = 6). (C) The number of platelets in the peripheral blood were quantified with an Advia coulter counter (n = 6). (D) Using flow cytometry, we detected a significant increase in the CD62P+ platelet activation level in the DTA group compared with the control at baseline (n = 4). (E) Representative histograms of CD62P+ platelet populations. (F) Fold change of CD62P+ platelet population relative to the control group (n = 4). (G) In vivo platelet clearance analysis of NHS-Biotin–labeled platelets over 6 days (n = 3–4). **P ≤ 0.01; ****P ≤ 0.0001. Two-tailed t tests were performed for A–G.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts