Function-based Enrichment of Pro-angiogenic Cells for Cardiac Repair

Lead Research Organisation: University of Bristol
Department Name: Clinical Science at South Bristol

Abstract

Heart disease is the most common course for death and illness across Europe. Standard therapy can rescue and preserve heart function only to a certain degree, still leaving the patient with a poor quality of life. Initial studies have tested the potential of injecting the patient s own bone marrow stem cells into the damaged heart muscle. We therefore know that the treatment is safe and can improve heart function more than classical therapy alone. However, researchers believe that the cells which are injected should be characterised and selected better to make sure they perform their supposed function.
In the proposed study, we want to select for cells which are able to actively travel towards a substance involved in attraction of regenerative stem cells. We have demonstrated before that this method can be used to isolate cells which have certain characteristics necessary for their beneficial action. However, the better function of the selected cells needs to be demonstrated in a mouse model mirroring the situation of the human patient.
Once we have shown that cells selected on the basis of their functional ability perform better than currently used cells, we will be in the position to develop a clinically applicable method improving the efficiency of stem cell therapy.

Technical Summary

Coronary heart disease remains the number 1 killer in developed countries. Regenerative medicine aims to repair the ischaemic heart, an objective not achieved with current interventions. Recent clinical trials have demonstrated the feasibility and safety of autologous bone marrow cell transplantation. However, the therapeutic potential remains below its potential. A main obstacle being the reduced regenerative potential of progenitor cells from patients with cardiovascular diseases. We recently developed a separation strategy based on a functional parameter ? migration towards a chemoattractant - whereby we have been able to enrich for pro-angiogenic progenitor cells. Moreover, using the same technique, we could obtain a cell population of equal in vitro potency from patients with acute myocardial infarction as from healthy controls. We now aim to validate and optimize the isolation procedure and verify the therapeutic potential of cells separated by migration in an animal model of myocardial infarction against two cell currently used populations. We expect that migration-enriched cells are superior to the two control cell populations currently in clinical use (total bone marrow cells and CD34+ progenitor cells) in their ability to induce re-vascularization in the infarcted myocardium, preserve a number and function of cardiomyocytes, and minimize scarring and inflammation. If validation satisfies expected outcomes, we will be in the position to develop a clinically applicable method improving the efficiency of stem cell therapy.