Cues from human atrial extracellular matrix enrich the atrial differentiation of human induced pluripotent stem cell-derived cardiomyocytes
| Autor: | Jacquelynn Morrissey, Gilberto B. Domont, Po-Feng Lee, Fábio C. S. Nogueira, Camila Hochman-Mendez, Yutao Xi, Doris A. Taylor, Fernanda C.P. Mesquita, Luiz C. Sampaio, Helen Andersson, Gustavo Monnerat |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Induced Pluripotent Stem Cells Cell Biomedical Engineering Endogeny 030204 cardiovascular system & hematology Extracellular matrix 03 medical and health sciences 0302 clinical medicine Tissue engineering Downregulation and upregulation medicine Humans Myocytes Cardiac General Materials Science Induced pluripotent stem cell 030304 developmental biology 0303 health sciences Decellularization Tissue Engineering Chemistry Cell Differentiation Phenotype Extracellular Matrix Cell biology medicine.anatomical_structure cardiovascular system Cues |
| Zdroj: | Biomaterials Science. 9:3737-3749 |
| ISSN: | 2047-4849 2047-4830 |
| Popis: | New robust and reproducible differentiation approaches are needed to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes of specific subtypes in predictable quantities for tissue-specific disease modeling, tissue engineering, and eventual clinical translation. Here, we assessed whether powdered decellularized extracellular matrix (dECM) particles contained chamber-specific cues that could direct the cardiac differentiation of human iPSCs toward an atrial phenotype. Human hearts were dissected and the left ventricle (LV) and left atria (LA) were isolated, minced, and decellularized using an adapted submersion decellularization technique to generate chamber-specific powdered dECM. Comparative proteomic analyses showed chamber-specific dECM segregation, with atrial- and ventricle-specific proteins uniquely present in powdered dECM-hA and dECM-hV, respectively. Cell populations differentiated in the presence of dECM-hA showed upregulated atrial molecular markers and a two-fold increase in the number of atrial-like cells as compared with cells differentiated with dECM-hV or no dECM (control). Finally, electrophysiological data showed an increase in action potentials characteristic of atrial-like cells in the dECM-hA group. These findings support the hypothesis that dECM powder derived from human atria retained endogenous cues to drive cardiac differentiation toward an atrial fate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|