TY - JOUR AU - Mendelson, Avital AU - Strat, Ana Nicolle AU - Bao, Weili AU - Rosston, Peter AU - Fallon, Georgia AU - Ohrn, Sophie AU - Zhong, Hui AU - Lobo, Cheryl AU - An, Xiuli AU - Yazdanbakhsh, Karina T1 - Mesenchymal stromal cells lower platelet activation and assist in platelet formation in vitro PY - 2019/08/22/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.126982 VL - 4 IS - 16 UR - https://doi.org/10.1172/jci.insight.126982 PB - The American Society for Clinical Investigation ER -