Grant Award Details
Develop a proof-of-concept biopacemaker consisting of hiPSC-derived cardiomyocytes in a porcine matrix scaffold from the sinoatrial node.
Grant Application Details
- Microenvironment for hiPSC-derived pacemaking cardiomyocytes
This proposal investigates the effects of the microenvironment on the development and maintenance of pacemaking function in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes.
Pacemaking function of hiPSC-derived cardiomyocytes is lost over time. Sustainability of pacemaking function of these cells is critical for engineering an biopacemaker from the patient's own cells.
Major Proposed Activities
- Determine the effects of matrix scaffolds on the differentiation and maintenance of pacemaking function in hiPSC-derived cardiomyocytes.
- Determine the appropriate hiPSC-derived cardiac cells to be subjected to the microenvironment for efficient yield of pacemaking hiPSC-derived cardiomyocytes.
- Induce vascularization in tissue constructs in small animals to sustain pacemaking tissue construct.
- Test sustainability of a functional pacemaking tissue construct in a small animal model.
Over 350,000 patients a year in the U.S. require an electronic pacemaker to restore their heart rhythm. The annual healthcare burden amounts to $20 billion. Repeated surgeries to replace battery and electrical parts generate additional costs and suffering for the patients. A biopacemaker engineered from human stem cell-derived pacemaking cells can overcome problems associated with electronics and improve the quality of life for the pacemaker recipient while reducing cumulative health care costs.
- Circ Arrhythm Electrophysiol (2021) Making Heads or Tails of the Large Mammalian Sinoatrial Node Micro-Organization. (PubMed: 34794338)
- Stem Cell Res (2020) NODAL inhibition promotes differentiation of pacemaker-like cardiomyocytes from human induced pluripotent stem cells. (PubMed: 33128951)
- Stem Cells (2020) An intrinsic, label-free signal for identifying stem cell-derived cardiomyocyte subtype. (PubMed: 31778240)
- Stem Cells (2019) Human induced pluripotent stem cell line with genetically encoded fluorescent voltage indicator generated via CRISPR for action potential assessment post-cardiogenesis. (PubMed: 31566285)