Grant Award Details
Microenvironment for hiPSC-derived pacemaking cardiomyocytes
<p style="text-align:justify;">Electronic pacemakers have numerous inherent deficiencies, such as limited sensitivity to changes in physical activities of recipients and necessary surgeries for battery replacement every 5-10 years for the recipients. Biopacemakers composed of human pacemaking cells similar to those in the native cardiac pacemaking tissue can circumvent these deficiencies that are inherent in the electronic devices. One potential source of human pacemaking cells is through derivation from the human induced pluripotent stem cells (hiPSCs). This award has enabled our laboratory to optimize the differentiation protocol and the microenvironment to induce hiPSC-derived heart cells to behave functionally more like the pacemaking rather than the contractile type. This is the first step towards having the right components for engineering biopacemakers.</p>
<p>Electronic pacemakers have numerous inherent deficiencies, such as limited sensitivity to changes in physical activities of recipients and necessary surgeries for battery replacement every 5-10 years for the recipients. Biopacemakers composed of human pacemaking cells similar to those in the native cardiac pacemaking tissue can circumvent these deficiencies that are inherent in the electronic devices. We proposed to develop pacemaking tissue constructs that may serve as biopacemakers by incorporating human induced pluripotent stem cell (hiPSC)-derived heart muscle cells in matrix scaffold from the pig pacemaking tissue, the sinoatrial node. In this study, we developed a new differentiation method that can yield up to 2.4 times more pacemaking heart muscle cells from the hiPSCs. We also demonstrated that the extracellular matrix environment is critical in inducing the pacemaking function and also in maintaining the function when subjected to cyclic mechanical strain that mimics the cardiac environment. Our research will continue to understand the mechanisms and the factors in the extracellular matrix of the native pacemaking tissue that resulted in the observed sustained pacemaking function in hiPSC-derived heart muscle cells.</p><p> </p>
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.
Statement of Benefit to California:
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.
Source URL: https://www.cirm.ca.gov/our-progress/awards/microenvironment-hipsc-derived-pacemaking-cardiomyocytes