Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes
Arrhythmias of the heart are currently treated by implanting electronic pacemakers and defibrillators. Unmodified adipose tissue-derived stem cells (ASCs) have the potential to differentiate into all three germ layers but have not yet been tested for the generation of pacemaker and Purkinje cells. W...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/10/1381 |
| _version_ | 1827741803691900928 |
|---|---|
| author | Tahereh Karimi Zhizhong Pan Vladimir N. Potaman Eckhard U. Alt |
| author_facet | Tahereh Karimi Zhizhong Pan Vladimir N. Potaman Eckhard U. Alt |
| author_sort | Tahereh Karimi |
| collection | DOAJ |
| description | Arrhythmias of the heart are currently treated by implanting electronic pacemakers and defibrillators. Unmodified adipose tissue-derived stem cells (ASCs) have the potential to differentiate into all three germ layers but have not yet been tested for the generation of pacemaker and Purkinje cells. We investigated if—based on overexpression of dominant conduction cell-specific genes in ASCs—biological pacemaker cells could be induced. Here we show that by overexpression of certain genes that are active during the natural development of the conduction system, the differentiation of ASCs to pacemaker and Purkinje-like cells is feasible. Our study revealed that the most effective procedure consisted of short-term upregulation of gene combinations SHOX2-TBX5-HCN2, and to a lesser extent SHOX2-TBX3-HCN2. Single-gene expression protocols were ineffective. Future clinical implantation of such pacemaker and Purkinje cells, derived from unmodified ASCs of the same patient, could open up new horizons for the treatment of arrythmias. |
| first_indexed | 2024-03-11T03:52:17Z |
| format | Article |
| id | doaj.art-fbdc82e43e5249cbba8c2dd1bd9afc9b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:52:17Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fbdc82e43e5249cbba8c2dd1bd9afc9b2023-11-18T00:52:46ZengMDPI AGCells2073-44092023-05-011210138110.3390/cells12101381Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental GenesTahereh Karimi0Zhizhong Pan1Vladimir N. Potaman2Eckhard U. Alt3Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, 1430 Tulane Ave, New Orleans, LA 70112, USAUniversity of Texas MD Anderson Cancer Center, Houston, TX 77030, USAAlliance of Cardiovascular Researchers, 2211 Augusta Dr #10, Houston, TX 77057, USAHeart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, 1430 Tulane Ave, New Orleans, LA 70112, USAArrhythmias of the heart are currently treated by implanting electronic pacemakers and defibrillators. Unmodified adipose tissue-derived stem cells (ASCs) have the potential to differentiate into all three germ layers but have not yet been tested for the generation of pacemaker and Purkinje cells. We investigated if—based on overexpression of dominant conduction cell-specific genes in ASCs—biological pacemaker cells could be induced. Here we show that by overexpression of certain genes that are active during the natural development of the conduction system, the differentiation of ASCs to pacemaker and Purkinje-like cells is feasible. Our study revealed that the most effective procedure consisted of short-term upregulation of gene combinations SHOX2-TBX5-HCN2, and to a lesser extent SHOX2-TBX3-HCN2. Single-gene expression protocols were ineffective. Future clinical implantation of such pacemaker and Purkinje cells, derived from unmodified ASCs of the same patient, could open up new horizons for the treatment of arrythmias.https://www.mdpi.com/2073-4409/12/10/1381adipose-derived stem cellstranscription factorsion channelspacemaker cells |
| spellingShingle | Tahereh Karimi Zhizhong Pan Vladimir N. Potaman Eckhard U. Alt Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes Cells adipose-derived stem cells transcription factors ion channels pacemaker cells |
| title | Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes |
| title_full | Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes |
| title_fullStr | Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes |
| title_full_unstemmed | Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes |
| title_short | Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes |
| title_sort | conversion of unmodified stem cells to pacemaker cells by overexpression of key developmental genes |
| topic | adipose-derived stem cells transcription factors ion channels pacemaker cells |
| url | https://www.mdpi.com/2073-4409/12/10/1381 |
| work_keys_str_mv | AT taherehkarimi conversionofunmodifiedstemcellstopacemakercellsbyoverexpressionofkeydevelopmentalgenes AT zhizhongpan conversionofunmodifiedstemcellstopacemakercellsbyoverexpressionofkeydevelopmentalgenes AT vladimirnpotaman conversionofunmodifiedstemcellstopacemakercellsbyoverexpressionofkeydevelopmentalgenes AT eckhardualt conversionofunmodifiedstemcellstopacemakercellsbyoverexpressionofkeydevelopmentalgenes |