| Autor: |
Charles M. Kerr, Sophia E. Silver, Yi Sun Choi, Martha E. Floy, Amy D. Bradshaw, Seung-Woo Cho, Sean P. Palecek, Ying Mei |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Bioactive Materials, Vol 31, Iss , Pp 463-474 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2452-199X |
| DOI: |
10.1016/j.bioactmat.2023.08.023 |
| Popis: |
Human induced pluripotent stem cell derived cardiac fibroblasts (hiPSC-CFs) play a critical role in modeling human cardiovascular diseases in vitro. However, current culture substrates used for hiPSC-CF differentiation and expansion, such as Matrigel and tissue culture plastic (TCPs), are tissue mismatched and may provide pathogenic cues. Here, we report that hiPSC-CFs differentiated on Matrigel and expanded on tissue culture plastic (M-TCP-iCFs) exhibit transcriptomic hallmarks of activated fibroblasts limiting their translational potential. To alleviate pathogenic activation of hiPSC-CFs, we utilized decellularized extracellular matrix derived from porcine heart extracellular matrix (HEM) to provide a biomimetic substrate for improving hiPSC-CF phenotypes. We show that hiPSC-CFs differentiated and expanded on HEM (HEM-iCFs) exhibited reduced expression of hallmark activated fibroblast markers versus M-TCP-iCFs while retaining their cardiac fibroblast phenotype. HEM-iCFs also maintained a reduction in expression of hallmark genes associated with pathogenic fibroblasts when seeded onto TCPs. Further, HEM-iCFs more homogenously integrated into an hiPSC-derived cardiac organoid model, resulting in improved cardiomyocyte sarcomere development. In conclusion, HEM provides an improved substrate for the differentiation and propagation of hiPSC-CFs for disease modeling. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
