delayed-intramyocardial-delivery-stem-cells-after-ischemia

Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model

There is significant interest in the use of stem cells (SCs) for the recovery of cardiac function in individuals with myocardial injuries. Most commonly, ...

Mayo Clinic

The maximal efficacy of cell therapy depends on the survival of stem cells, as well as on the phenotypic and biologic changes that may occur on these cells after transplantation. It has been hypothesized that the post-ischemic myocardial microenvironment can play a critical role in these changes, potentially affecting the survival and reparative potential of mesenchymal stem cells (MSCs). Here, we use a dual reporter gene sensor for the in vivo monitoring of the phenotype of MSCs and study their therapeutic effect on cardiac function.

The Myocardial Microenvironment Modulates the Biology of Transplanted Mesenchymal Stem Cells.

Little is known on the phenotypic characteristics of stem cells (SCs) after they are transplanted to the myocardium, in part due to lack of noninvasive platforms to study SCs directly in the living subject. Reporter gene imaging has played a valuable role in the noninvasive assessment of cell fate in vivo. In this study, we validated a pathway-specific reporter gene that can be used to noninvasively image the phenotype of SCs transplanted to the myocardium. Rat mesenchymal SCs (MSCs) were studied for phenotypic evidence of myogenic characteristics under in vitro conditions. After markers of myogenic characteristics were identified, we constructed a reporter gene sensor, comprising the firefly luciferase (Fluc) reporter gene driven by the troponin T (TnT) promoter (cardio MSCs had threefold expression in polymerase chain reaction compared to control MSCs) using a two-step signal amplification strategy. MSCs transfected with TnT-Fluc were studied and validated under in vitro conditions, showing a strong signal after MSCs acquired myogenic characteristics. Lastly, we observed that cardio MSCs had higher expression of the reporter sensor compared to control cells (0.005 ± 0.0005 vs 0.0025 ± 0.0008 Tnt-Fluc/ubiquitin-Fluc, P < .05), and that this novel sensor can detect the change in the phenotype of MSCs directly in the living subject. Pathway-specific reporter gene imaging allows assessment of changes in the phenotype of MSCs after delivery to the ischemic myocardium, providing important information on the phenotype of these cells. Imaging sensors like the one described here are critical to better understanding of the changes that SCs undergo after transplantation.

Article	Year
The Myocardial Microenvironment Modulates the Biology of Transplanted Mesenchymal Stem Cells. Molecular imaging and biology\| PubMed ID: 31907845	2020
Pathway-specific reporter genes to study stem cell biology. Stem cells (Dayton, Ohio)\| PubMed ID: 32129537	2020

Michaela Olthoff

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