Thrombotic Risk Associated with Intravenous Mesenchymal Stromal Cell Administration: Mechanisms, Clinical Evidence, and Prevention Strategies

Joon Lee, Yong-Beom Park, Seong Ji Su and Jin A Kim*
 

Geniecellbio Co., Ltd., Seongnam, Republic of Korea
DOD Dermatology Clinic, Seoul, Republic of Korea
School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea
Corporate Research Institute, Placeuticals Co., Ltd., Seongnam, Republic of Korea
Department of Orthopedic Surgery, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College
of Medicine, Seoul, Republic of Korea
Department of Obstetrics and Gynecology, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University
College of Medicine, Seoul, Republic of Korea

^*Correspondance to: Jin A Kim 

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Abstract:

Mesenchymal Stromal Cells (MSCs) are increasingly investigated as systemic cell therapies because of their immunomodulatory, anti-inflammatory, and regenerative properties. Although Intravenous (IV) administration is convenient and widely used, direct exposure of MSCs to circulating blood raises concerns regarding coagulation activation, pulmonary microvascular obstruction, and thromboembolic complications. MSCs can express Tissue Factor (TF/CD142), expose procoagulant Phosphatidylserine (PS), and interact with coagulation, complement, platelets, and innate immune pathways. Their relatively large size also promotes initial pulmonary retention following IV infusion. These biological effects are influenced by tissue source, donor characteristics, culture and expansion conditions, cryopreservation and post-thaw handling, cell viability and aggregation, dose, concentration, and administration conditions. Clinically significant thrombotic complications have been reported, and transient or subclinical coagulation activation may occur without overt thrombosis. However, controlled clinical trials and systematic reviews have not demonstrated a consistent increase in clinically significant thrombotic or thromboembolic events following intravascular MSC administration. These findings indicate that procoagulant potential, subclinical coagulation activation, and clinically manifest thrombosis are related but distinct outcomes. TF/CD142 is an important mechanistic and product-related risk attribute but is insufficient as a stand-alone predictor of clinical thrombotic risk. A comprehensive patient-product-administration risk-based approach integrating patient-specific thrombotic susceptibility, product characterization, functional hemocompatibility assessment, product-specific dose and administration procedures, and appropriate peri-infusion monitoring may provide a more rational framework for risk mitigation. This review summarizes the mechanisms underlying thrombotic and microembolic risks associated with IV MSC administration, evaluates the available clinical evidence, and discusses current and emerging strategies for safer systemic MSC therapy.

Keywords:

Mesenchymal stromal cells; Intravenous administration; Thrombosis; Tissue factor; Coagulation; Hemocompatibility

Cite the Article:

Lee J, Park Y-B, Su SJ, Kim JA. Thrombotic Risk Associated with Intravenous Mesenchymal Stromal Cell Administration: Mechanisms, Clinical Evidence, and Prevention Strategies. Clin Case Rep Int. 2026; 10: 1791.