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        Biomaterials-based Approaches for Cardiac Regeneration

        Samhita Vasu,Justin Zhou,Jeffrey Chen,Peter V. Johnston,Deok-Ho Kim 대한심장학회 2021 Korean Circulation Journal Vol.51 No.12

        The limited ability of cardiomyocytes to proliferate is a major cause of mortality and morbidity in cardiovascular diseases. There exist therapies for cardiac regeneration that are cell-based as well as that involve bioactive molecules. However, delivery remains one of the major challenges impeding such therapies from having clinical impact. Recent advancements in biomaterials-based approaches for cardiac regeneration have shown promise in clinical trials and animal studies in improving cardiac function, promoting angiogenesis, and reducing adverse immune response. This review will focus on current clinical studies of three contemporary biomaterials-based approaches for cardiac regeneration (extracellular vesicles, injectable hydrogels, and cardiac patches), remaining challenges and shortcomings to be overcome, and future directions for the use of biomaterials to promote cardiac regeneration.

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        Molecular Imaging of CXCL12 Promoter-driven HSV1-TK Reporter Gene Expression

        Lina Alon,Dara L. Kraitchman,Michael Schär,Angel Cortez,Nirbhay N. Yadav,Rebecca Krimins,Peter V. Johnston,Michael T. McMahon,Peter C. M. van Zijl,Sridhar Nimmagadda,Martin G. Pomper,Jeff W. M. Bulte 한국생물공학회 2018 Biotechnology and Bioprocess Engineering Vol.23 No.2

        The C-X-C motif chemokine 12 (CXCL12, SDF1a) and its receptor, CXCR4, play a fundamental role in several biological processes, including hematopoiesis, cardiogenesis, cancer progression, and stem cell migration. Noninvasive monitoring of CXCL12 is highly desirable for optimizing strategies that combine mobilization of therapeutic cells to combat cancer or to assist in cardiac tissue repair after myocardial infarction. Here, we report on an MRI reporter gene system for directly monitoring CXCL12 expression in vivo. Glioma cells and human adipose-derived stem cells (hADSC) were transduced with the herpes simplex virus type-1-thymidine kinase (HSV1- tk) reporter gene expressed under the CXCL12 promoter. HSV1-tk expression resulted in accumulation of the PET tracer [125I]FIAU in vitro and in vivo and induced cell death after ganciclovir treatment. Furthermore, the results show that conditional expression of the reporter gene can be induced by hypoxia in transduced cells. Transduced hADSC were incubated with the CEST MRI probe 5-methyl-5, 6- dihydrothymidine (5-MDHT) and transplanted into swine heart. Transplanted cells were clearly visible on Chemical Exchange Saturation Transfer (CEST) MRI using a 3T clinical scanner. Therefore, we conclude that it is possible to image CXCL12 expression with MRI in a large animal model, opening up a possible route to clinical translation.

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