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.
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Research Article Hematology Stem cells

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

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

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Figure 8

cMSCs assist in promoting proplatelet formation and decrease platelet activation.

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cMSCs assist in promoting proplatelet formation and decrease platelet ac...
(A–C) Megakaryocytes from cMSC coculture group had decreased gene expression, as measured by real-time PCR, for SRC (A), DIAPH1 (B), and BAX (C), which are associated with increased megakaryocyte maturation (n = 3–4). (D and E) Furthermore, megakaryocytes from cMSC coculture group had decreased gene expression for LAT1 (D) and enriched for expression of RAP1B (E) relative to platelets from the control cultures, suggesting that cMSCs help to keep megakaryocytes in a lower activation state (n = 3–4). (F–H) Platelets from cMSC coculture group had increased protein expression, as measured by reverse phase protein analysis (RPPA), for IRF1 (F), STAT3 (G), and CCND3 (H), relative to platelets from the control cultures, suggesting that cMSCs are able to promote megakaryocyte maturation (n = 7–8). *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001. Two-tailed t tests were performed.