Developing next-generation biologic pacemakers

December 16, 2019

University of Houston associate professor of pharmacology Bradley McConnell is helping usher in a new age of cardiac pacemakers by using stem cells found in fat, converting them to heart cells, and reprogramming those to act as biologic pacemaker cells. He is reporting his work in the Journal of Molecular and Cellular Cardiology. The new biologic pacemaker-like cell will be useful as an alternative treatment for conduction system disorders, cardiac repair after a heart attack and to bridge the limitations of the electronic pacemaker.

"We are reprogramming the cardiac progenitor cell and guiding it to become a conducting cell of the heart to conduct electrical current," said McConnell.

McConnell's collaborator, Robert J. Schwartz, Hugh Roy and Lillian Cranz Cullen Distinguished Professor of biology and biochemistry, previously reported work on turning the adipogenic mesenchymal stem cells, that reside in fat cells, into cardiac progenitor cells. Now those same cardiac progenitor cells are being programmed to keep hearts beating as a sinoatrial node (SAN), part of the electrical cardiac conduction system (CCS).

The SAN is the primary pacemaker of the heart, responsible for generating the electric impulse or beat. Native cardiac pacemaker cells are confined within the SAN, a small structure comprised of just a few thousand specialized pacemaker cells. Failure of the SAN or a block at any point in the CCS results in arrhythmias.

More than 600,000 electronic pacemakers are implanted in patients annually to help control abnormal heart rhythms. The small mechanical device is placed in the chest or abdomen and uses electrical pulses to prompt the heart to beat normally. In addition to having the device regularly examined by a physician, over time an electronic pacemaker can stop working properly.

"Batteries will die. Just look at your smartphone," said McConnell. "This biologic pacemaker is better able to adapt to the body and would not have to be maintained by a physician. It is not a foreign object. It would be able to grow with the body and become much more responsive to what the body is doing."

To convert the cardiac progenitor cells, McConnell infused the cells with a unique cocktail of three transcription factors and a plasma membrane channel protein to reprogram the heart cells in vitro.

"In our study, we observed that the SHOX2, HCN2, and TBX5 (SHT5) cocktail of transcription factors and channel protein reprogrammed the cells into pacemaker-like cells. The combination will facilitate the development of cell-based therapies for various cardiac conduction diseases," he reported.
Suchi Raghunathan, doctoral student in the UH Department of Pharmacological and Pharmaceutical Sciences in the College of Pharmacy, is the paper's first author.

University of Houston

Related Transcription Factors Articles from Brightsurf:

Circular RNA regulates neuronal differentiation by scaffolding an inhibitory transcription complex
In a screening for a functional impact to the neuronal differentiation process, Danish researchers identified a specific circular RNA, circZNF827, which surprisingly 'taps the brake' on neurogenesis.

Transcription factors may inadvertently lock in DNA mistakes
A team of Duke researchers has found that transcription factors have a tendency to bind strongly to ''mismatched'' sections of DNA, i.e. sections of the genome that were not copied correctly.

New role assigned to a human protein in transcription and genome stability
DNA-RNA hybrids, or R loops, are structures that generate genomic instability, a common feature of tumor cells.

CeMM study reveals how a master regulator of gene transcription operates
Using TPD technology, CeMM researchers set out to understand set out to understand the primary role of a key regulator of transcription, the human Mediator complex.

Researchers find new role for dopamine in gene transcription and cell proliferation
A joint group of researchers at the George Washington University and the University of Pittsburgh have found that dopamine and the dopamine D2 receptor modulate expression via the Wnt/β-catenin signaling pathway.

SMAD2 and SMAD3, two almost identical transcription factors but with distinct roles
Both transcription factors regulate the expression of genes involved in embryo development, among other functions, although they exert very different roles.

Study explores role of mediator protein complex in transcription and gene expression
A new study led by Ryerson University called 'The Med31 Conserved Component of the Divergent Mediator Complex in Tetrahymena thermophila Participates in Developmental Regulation' advances existing knowledge about transcription and gene expression.

New members found in a transcription factor complex that maintains beta cells
A protein complex in the nucleus of beta cells contains different proteins that work together to regulate genes important for the development and maintenance of functional beta cells.

Testifying while black: A linguistic analysis of disparities in court transcription
A new study has found that court reporters transcribe speakers of African American English significantly below their required level of accuracy.

Transcription factor network gets to heart of wood formation
Research on high-level switches that control wood formation has applications in timber, paper and biofuels, as well as making forests healthier.

Read More: Transcription Factors News and Transcription Factors Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to