Myocardial infarction may lead to loss of billions of cardiomyocytes responsible for cardiac contractility and pumping function. Due to the limited ability of the adult heart to regenerate and repair itself, the loss of cardiomyocytes leaves the heart unable to meet or respond to the demands of tissues with adequate blood supply.
MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs, and have been shown to play a fundamental role in cardiovascular biology. Although implicated also in cardiac repair and regeneration, details on their function and molecular mechanisms in regulating these processes are only beginning to emerge.
The main objective of this project is to evaluate the potential of novel miRNA-targeted pharmaceutical agents to serve as novel drug target for cardiovascular diseases.
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Replacement of lost cardiomyocytes is a primary target of regenerative medicine for patients suffering from myocardial infarction. There are several approaches of deriving functional cardiomyocytes using e.g. stem cells, but eventually they all require thorough characterization of the cardiomyocyte's electrophysiological properties, to identify the specific phenotype (nodal, atrial and ventricular) of the differentiated cell. Current methods for this purpose are limited and novel methodologies are required for allowing the measurement of membrane potentials of cardiomyocytes in cell monolayers or intact tissues. Optogenetics is a powerful tool that combines optical stimulation of cells that have been engineered to express light sensing proteins that function as ion channels in the cell membrane. Action potentials can thus be measured with high specificity and high spatiotemporal resolution simply by exposing these cells/tissues to light and measuring their emitted fluorescence, without the need for invasive electrodes. In addition, the technique permits simultaneous measurements of intracellular calcium as well as optical pacing.
Our goal is to establish a technology that allows for high throughput electrophysiological characterization of cardiomyocytes (stem cell-derived or from human heart biopsies), in order to delineate the distinct electrophysiological profile of the cells. We also want to explore the use of optogenetics in regenerative heart research as a tool to reprogram stem cells into a cardiomyocyte lineage.
Cell therapy or cell-based therapy in a wider perspective, aim for a targeted treatment of heart failure and functional reconstitution by replacing or regenerating the dysfunctional myocardial tissue. A variety of cell types and cell-derived mediators have been evaluated both experimentally and clinically, but these have shown limited benefit.
This translational project aims at developing autologous cost-effective cell therapy that can be produced and administered in conjunction with cardiac surgery, for example during coronary artery bypass grafting (CABG). The project builds on expertise from clinical and experimental cell therapy research as well as on both national and international collaboration.
Treatment of large wounds, such as burn wounds frequently requires hospitalization and intensive care for extended periods of time. Autologous skin grafting is a surgical procedure where a thin layer of healthy skin is harvested from a patient to cover and replace tissue defect due to e.g. burn injury. Regeneration of skin is, however, not without complications.
There may be limited sites for harvesting available, and the graft may need to be expanded by meshing. The graft may adhere poorly to the wound and depending on the extent of expansion by meshing, skin regeneration through cell migration from the graft edges can be slow and compromised. This can result in incomplete regeneration and healing as well as formation of brittle scar tissue.
This translational project develops cell therapies to enhance success and outcome of skin grafting in especially burn wounds.
This project: "Action on Human Surfaces: Wound-Metatranscriptomics" is also called Bugsy. The aim of this consortium is to advantage the understanding of the etiology of surgical site infections and develop cost-effective next-generation sequencing based solutions to facilitate individualized treatment and early recognition of hospital-acquired infections. In this truly multidisciplinary research initiative, patient samples collected at the Helsinki University Hospital are analyzed by the researchers of FIMM, the Institute of Biotechnology, Department of Pharmacology, and Department of Food and Environmental Sciences, University of Helsinki. Project is part of the Personalised Health – From Genes to Society (pHealth)-program of the Academy of Finland.