Frequently Asked Questions

Biological pacemaker and implantation catheter

Inventors:  Syde A. Taheri, Howard J. Leonhardt
US Patent 6690970 B1

A biological pacemaker and implantation catheter for restoring normal or near normal heartbeat function without a mechanical pacemaker. The biological pacemaker is provided by a bridge of implantation cells, such as nerve cells, stem cells or ganglion cells, that are introduced into an area of electrical malfunction, such as an impaired SA node or a blocked AV node. The implantation cells grow to form a conductive cell bridge around the malfunction area so that a new pathway is provided for the electrical signals responsible for triggering heart beat contractions.

What is the BioPace therapy?
The BioPace therapy has been developed to restore natural pacemaking function to the heart of patients suffering from abnormal cardiac rhythms. The BioPace therapy consists of implanting a tiny dissolvable bioreactor chamber, containing patient-specific pacemaker cells, into strategic regions of the heart in order to restore and regenerate the patient’s own natural biological pacing. Once placed, the pacemaker cells within the bioreactor will be supported and maintained via a combination of bioelectric signaling coupled with the infusion of key biologicals made up of key cytokines, growth factors, and stem cells engineered to support optimal cell function, cell growth, and tissue integration.
What studies have been done?
BioPace completed studies on 3 large animals and demonstrated an ability to restore natural pacing after injection of cultured Sino Atrial Node cells. In attempting to repeat these studies the team ran into difficulty managing cell survival, differentiation, engraftment, and migration. In lab studies the team has identified that a combination of bioelectric stimulation, biologics, stem cells and an implantable bioreactor chamber has potential to improve upon the naked stand-alone cultured one-time cell injections tested in the first phase. More studies are needed to confirm whether these proposed improvements do indeed improve results.

In vitro, we have demonstrated that functional coupling can occur between cardiocytes and other cell types across multi-perforated membranes patented as PerFLexMEA. These studies demonstrate that pacemaker cells held within a scaffold can communicate with cardiocytes outside the scaffold to stimulate and pace the heart.

We have also characterized (in vitro) the pharmacological response of cardiocytes. In a study published by [INSERT AUTHOR ET AL] in [INSERT JOURNAL TITLE], blood macrophages were successfully transformed into cardiocytes, which responded differentially to antiarrhythmic drugs.

What does bioelectric stimulation attempt to do?
There are two purposes for bioelectric stimulation in the BioPace therapeutic platform.

First, bioelectric stimulation will be used to train engineered autorhythmic cells within the scaffold to beat at different rates, depending on the patient. Younger patients can require basal beating frequencies close to 250 bpm while older patients may require a basal frequency of 60 – 70 bpm.

Second, bioelectric stimulation can be used after the implantation of the BioPace scaffold to:
1. Home stem cells to treatment site via expressions of SDF1 and PDGF.
2. Release growth factors such as VEGF, PDGF, SDF1, HGF, EGF, CXCL5 and eNOS to improve blood supply to treated region.
3. Releases factors known to promote regeneration such as Klotho and IGF1.
4. Promotes proliferation of stem cells on demand.
5. Promotes controlled differentiation of cells.
6. Trains newly formed pacing cells to pace in synchrony with heart.

What components may be included in repeat infusion mixes?
The BioPace team is working on the final mixed composition for generating or regenerating natural pacemaker formation. Included on test candidates list are iPS cells, adipose derived stem cells, stromal fraction, selected exosomes, selected growth factors such as klotho and SDF1, MicroRNA gel, nutrient hydrogel, oxygenated nano particles, Sino Atrial nodal matrix, and atrial myocytes matrix. The BioPace technology platform includes methods of cell culturing, including electrical stimulation enhanced cell culturing with platelet derived freeze thaw extract and other growth factors, to influence the phenotype towards pacing cell types.