Si, Yaqing and Fan, Yuxuan and Scheller, Leo and Stefanov, Bozhidar-Adrian and Lv, Jian and Wang, Zhihua and Xie, Mingqi and Fussenegger, Martin (2026) Engineering mammalian cells for detection and treatment of cardiac injury. MOLECULAR SYSTEMS BIOLOGY, 22 (1). pp. 88-101. ISSN 1744-4292,
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Early detection of myocardial abnormalities or other ischemic heart diseases is critical for effective treatment. Here, we aimed to engineer a cell-based system to sense cardiac troponin I (cTnI), an early marker of acute myocardial infarction (AMI), and respond by releasing a thrombolytic agent. To detect cTnI, we engineered a chimeric troponin receptor (TropR) that contains extracellular single-chain variable fragments (scFvs) and signals via intracellular domains of interleukin 6 receptor subunit beta (IL6RB), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2b (FGFR2b) or vascular endothelial growth factor receptor 2 (VEGFR2) that are associated with cardioprotective signaling. cTnI-dependent TropR functionality was confirmed in human embryonic kidney (HEK)-derived cell lines as well as iPSC-derived cardiomyocytes, and enabled rapid, reversible, tunable control of gene expression via synthetic-signaling-specific promoters. We then constructed monoclonal cell lines for cTnI-induced secretion of the thrombolytic protein tenecteplase (TNK), together with an off-switch triggered by FDA-approved doxycycline. We selected a clone, designated CardioProtect, whose sensitivity was optimized to detect human AMI-relevant cTnI levels. To validate thrombolytic efficacy, we established an ex vivo blood culture system and show that alginate-microencapsulated CardioProtect cells triggered complete lysis of fibrin clots in a strict cTnI-inducible, doxycycline-repressible manner. This closed-loop strategy serves as a proof-of-concept for using cell therapy in the early detection and treatment of AMI.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MYOCARDIAL-INFARCTION; TROPONIN; TENECTEPLASE; ACTIVATION; MORTALITY; ANTIBODY; MODELS; RATES; VIVO; CARE; Cardiac Troponin; Acute Myocardial Infarction; Synthetic Receptors; Designer Cells; Thrombolysis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2026 13:58 |
| Last Modified: | 23 Mar 2026 13:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/68087 |
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