Despite their success, several limitations and problems with artificial pacemakers have emerged during the past decades such as electrode fracture or damage to insulation, infection, re-operations for battery exchange, and venous thrombosis.
[1] The first successful experiment with biological pacemakers was carried out by Arjang Ruhparwar 's group at Hannover Medical School in Germany using transplanted fetal heart muscle cells.
[4] A few months later, Eduardo Marban's group from Johns Hopkins University published the first successful gene-therapeutic approach towards the generation of pacemaking activity in otherwise non-pacemaking adult cardiomyocytes using a guinea pig model.
By specific inhibition of Ik1 below a certain level, spontaneous activity of cardiomyocytes was observed with resemblance to the action potential pattern of genuine pacemaker cells.
Michael Rosen's group demonstrated that transplantation of HCN2-transfected human mesenchymal stem cells (hMSCs) leads to expression of functional HCN2 channels in vitro and in vivo, mimicking overexpression of HCN2 genes in cardiac myocytes.