Recombinant thrombomodulin of different domains for pharmaceutical, biomedical, and cell transplantation applications

Thrombomodulin (TM) is a membrane glycoprotein mainly expressed by vascular endothelial cells and is involved in many physiological and pathological processes, such as coagulation, inflammation, cancer development, and embryogenesis. Human TM consists of 557 amino acids divided into five distinct domains: N-terminal lectin-like domain (designated as TMD1); six epidermal growth factor (EGF)-like domain (TMD2); Ser/Thr-rich domain (TMD3); transmembrane domain (TMD4); and cytoplasmic tail domain (TMD5). The different domains are responsible for different biological functions of TM. In the past decades, various domains of TM have been cloned and expressed for TM structural and functional study. Further, recombinant TMs of different domains show promising antithrombotic and anti-inflammatory activity in both rodents and primates and a recombinant soluble TM has been approved for therapeutic application. This review highlights recombinant TMs of diverse structures and their biological functions, as well as the complex interactions of TM with factors involved in the related biological processes. Particularly, recent advances in exploring recombinant TM of different domains for pharmaceutical, biomedical, and cell transplantation applications are summarized.