Decellularized heart extracellular matrix alleviates activation of hiPSC-derived cardiac fibroblasts.
Decellularized heart extracellular matrix alleviates activation of hiPSC-derived cardiac fibroblasts.
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DOI：
10.1016/j.bioactmat.2023.08.023
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发表时间：
2024-01
影响因子：
18.9
通讯作者：
中科院分区：
文献类型：
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作者：
人诱导多能干细胞来源的心脏成纤维细胞（hiPSC-CFs）在体外模拟人类心血管疾病中起关键作用。然而，目前用于hiPSC-CF分化和扩增的培养基质，如基质胶和组织培养塑料（TCP），是组织不匹配的，并且可能提供致病线索。在这里，我们报告了在基质胶上分化并在组织培养塑料（M-TCP-iCF）上扩增的hiPSC-CF表现出活化成纤维细胞的转录组学标志，限制了它们的翻译潜力。为了减轻hiPSC-CF的致病性活化，我们利用来源于猪心细胞外基质（HEM）的脱细胞外基质来提供用于改善hiPSC-CF表型的仿生底物。我们表明，在HEM上分化和扩增的hiPSC-CF（HEM-iCF）表现出与M-TCP-iCF相比标志物活化的成纤维细胞标志物的表达降低，同时保留其心脏成纤维细胞表型。当接种到TCP上时，HEM-iCF还保持了与致病性成纤维细胞相关的标志基因表达的降低。此外，HEM-iCF更均匀地整合到hiPSC衍生的心脏类器官模型中，导致改善的心肌细胞肌节发育。总之，HEM为疾病建模的hiPSC-CF的分化和增殖提供了改进的底物。用于衍生hiPSC-心脏成纤维细胞的常见组织培养基质诱导致病性表型的活化。仿生猪心细胞外基质（HEM）减少并防止hiPSC-CF的致病性活化。HEM不损害hiPSC-CF的心脏成纤维细胞表型。HEM衍生的hiPSC-CF在hiPSC心脏类器官模型中显示增强的整合和改善的心肌细胞发育。
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. Common tissue culture substrates for the derivation of hiPSC-cardiac fibroblasts induce activation of pathogenic phenotypes. Biomimetic porcine heart extracellular matrix (HEM) reduced and prevented pathogenic activation of hiPSC-CFs. HEM did not impair the cardiac fibroblast phenotype of hiPSC-CFs. HEM-derived hiPSC-CFs showed enhanced integration and improved cardiomyocyte development in an hiPSC cardiac organoid model.
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DOI：
10.1016/s0140-6736(18)32203-7
发表时间：
2018-11-10
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2017 Causes of Death Collaborators
通讯作者：
GBD 2017 Causes of Death Collaborators
DOI：
10.1096/fj.202100523r
发表时间：
2021-09
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Floy ME;Givens SE;Matthys OB;Mateyka TD;Kerr CM;Steinberg AB;Silva AC;Zhang J;Mei Y;Ogle BM;McDevitt TC;Kamp TJ;Palecek SP
通讯作者：
Palecek SP
人类3D心脏微动物的表征和验证，以评估心脏病理变化。
影响因子：
4.6
作者：
Archer CR;Sargeant R;Basak J;Pilling J;Barnes JR;Pointon A
通讯作者：
Pointon A
用脱细胞外基质支架控制干细胞行为。
DOI：
10.1016/j.cossms.2016.02.001
发表时间：
2016-08
影响因子：
11
作者：
Agmon G;Christman KL
通讯作者：
Christman KL
影响因子：
3
作者：
Baum J;Duffy HS
通讯作者：
Duffy HS