CHA Advanced Research Institute, Republic of Korea
Abstract: Thrombocytopenia, a hematological disorder marked by a significant reduction in circulating platelets, compromises hemostasis and increases the risk of uncontrolled bleeding. Current therapies, such as platelet transfusions, are limited by short shelf life, donor dependency, and immunological complications. Megakaryocytes (MKs), the precursor cells for platelet production, offer a promising alternative. Here, we evaluated the therapeutic potential of human pluripotent stem cell-derived megakaryocytes (PS-MKs) in restoring platelet function. A thrombocytopenic mouse model was established using NSG immunodeficient mice with busulfan-induced myelosuppression. PS-MKs were differentiated in vitro over five weeks and administered intravenously to evaluate their efficacy in vivo. Transplanted PS-MKs significantly reduced bleeding time, demonstrating effective restoration of hemostasis. Engraftment and platelet release were assessed over 72 hours. Nuclear DNA (GAPDH) from PS-MKs was detected exclusively in lung tissue up to 24 hours post-injection, indicating successful engraftment, with no nuclear DNA detected in the blood. Mitochondrial DNA (mtDNA), however, was detected in both lungs and blood, suggesting sustained platelet release. PKH26-labeled PS-MKs confirmed active lung migration post-injection, supporting their role in platelet production and hemostatic recovery. These results highlight the potential of PS-MKs as a renewable, scalable, and effective alternative to conventional platelet transfusions, offering a novel therapeutic approach for managing thrombocytopenia.
Funding Source: This research was supported by a grant of Korean Cell-Based Artificial Blood Project funded by the Korean government (grant number: RS-2023-KH140925)
