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SPAPPACDLRVLSKLLRDSHVLHSRLSQCPEVHPLPTPVLLPAVDFSLG EWKTQMEETKAQDILGAVTLLLEGVMAARGQLGPTCLSSLLGQLSGQV RLLLGALQSLLGTQLPPQGRTTAHKDPNAIFLSFQHLLRGKVRFLMLVGG STLCVRRAPPTTAVPSRTSLVLTLNELPNRTSGLLETNFTASARTTGSGLLK WQQGFRAKIPGLLNQTSRSLDQIPGYLNRIHELLNGTRGLFPGPSRRTLGAP DISSGTSDTGSLPPNLQPGYSPSPTHPPTGQYTLFPLPPTLPTPVVQLHPLLPDPSAPTPT
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Thrombopoietin was first purified in 1994, and since then, two recombinant forms have been developed: recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) . These recombinant forms have undergone extensive clinical investigation and have shown significant potential in stimulating megakaryocyte growth and platelet production .
Thrombopoietin binds to its receptor, TpoR (also known as c-Mpl), on the surface of megakaryocytes and their progenitors. This binding activates several intracellular signaling pathways, including the JAK-STAT, MAPK, and PI3K-AKT pathways, which promote the survival, proliferation, and differentiation of megakaryocytes .
Recombinant human thrombopoietin (rhTPO) has been investigated for its potential to treat various conditions associated with thrombocytopenia (low platelet count). These conditions include:
Recombinant human thrombopoietin is produced using various expression systems, including Chinese hamster ovary (CHO) cells and human embryonic kidney (HEK) cells. The HEK cell system is particularly advantageous due to its ability to produce glycosylated proteins that closely resemble their natural counterparts .
Ongoing and future studies aim to further define the clinical role of recombinant TPO and TPO mimetics in the treatment of chemotherapy- and nonchemotherapy-induced thrombocytopenia . Additionally, research is being conducted to explore the potential of TPO in ex vivo expansion of pluripotent stem cells and as a radioprotectant .