Cell therapy, including human mesenchymal stem cell (hMSC) therapy, has the potential to treat different pathologies, including myocardial infarctions (heart attacks). Biological sutures composed of fibrin have been shown to effectively deliver hMSCs to infarcted hearts. However, hMSCs rapidly degrade fibrin making cell seeding and delivery time sensitive. To delay the degradation process, we propose using aprotinin, a proteolytic enzyme inhibitor that has been shown to slow fibrinolysis. This project investigated the effects of aprotinin on hMSCs and suture integrity. Viability of hMSCs incubated with aprotinin, examined using a LIVE/DEAD stain, was similar to controls. No differences in proliferation, as determined by Ki-67 presence, and were observed. hMSCs incubated in aprotinin differentiated into adipocytes, osteocytes, and chondrocytes, confirming multipotency. CyQuant assays were used to determine the number of cells adhered to fibrin sutures. The number of adhered cells was increased through aprotinin supplementation at Days 2, 3, and 5 time points. To examine the effect of aprotinin on suture integrity, sutures were loaded to failure to determine ultimate tensile strength (UTS) and modulus (E). Sutures exposed to aprotinin had higher UTS and E when compared to sutures exposed to standard growth media. Degradation of fibrin was quantified using an ELISA to quantify fibrin degradation products (FDP) and by measuring suture diameter. Fibrin sutures incubated in aprotinin had larger diameters and less FDP compared to the controls, confirming decreased fibrinolysis. These data suggest that aprotinin can reduce degradation of biological sutures, providing a novel method for extending the implantation window and increasing the number of cells delivered for hMSC seeded biological sutures.
Worcester Polytechnic Institute
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Coffin, Spencer, "Extending the Window of Use for Human Mesenchymal Stem Cell Seeded Biological Sutures" (2015). Masters Theses (All Theses, All Years). 510.
fibrin sutures, human mesenchymal stem cells, fibrinolysis, regenerative medicine