Decellularized Wharton's jelly extracellular matrix as a promising scaffold for promoting hepatic differentiation of human induced pluripotent stem cells

2018 ◽  
Vol 120 (4) ◽  
pp. 6683-6697 ◽  
Author(s):  
Mousa Kehtari ◽  
Bahareh Beiki ◽  
Bahman Zeynali ◽  
Fatemeh Sadat Hosseini ◽  
Fatemeh Soleimanifar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Wharton’S Jelly ◽  
Hepatic Differentiation ◽  
Wharton's Jelly ◽  
Induced Pluripotent

scholarly journals Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

2016 ◽  
Vol 5 (1) ◽  
pp. 235-248 ◽  
Author(s):  
Nora Freyer ◽  
Fanny Knöspel ◽  
Nadja Strahl ◽  
Leila Amini ◽  
Petra Schrade ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Hepatic Differentiation ◽  
Induced Pluripotent

scholarly journals Modeling Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism dementia Complex with Microglia Containing Cerebral Organoids Derived from Induced Pluripotent Stem Cells

2021 ◽  
Author(s):  
Yiling Hong ◽  
Xu Dong ◽  
Lawrence Chang ◽  
Mariann Chang ◽  
Chen Xie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
M2 Microglia ◽  
Matrix Organization ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism dementia Complex (ALS-PDC) is a neurodegenerative disease linked to the traditional consumption of cycad seeds by the Chamorro people of Guam. Little is known about the etiological role of cycad toxin in ALS-PDC. Patient derived induced pluripotent stem cells were derived from age and sex matched affected and unaffected patient lymphoid cells then differentiated into cerebral organoids. After three months, the ALS-PDC affected organoids were smaller, their neurons had less extensive neurite outgrowth, and the organoids had more reactive astrocytes and M1 microglia, fewer resting and M2 microglia, and more open extracellular space. Most of these phenomena could be recapitulated by exposing unaffected organoids to β-methylamino L-alanine (BMAA), a toxic amino acid produced by cyanobacteria living with cycad plants. Furthermore, ALS-PDC affected organoids exhibited an exacerbated neuroinflammatory response to BMAA exposure via activation of caspase1/NLRP3 inflammasome. A genome-wide transcriptome analysis of the organoids showed that the most down regulated pathways were taurine, alanine, aspartate, and glutamate metabolism; protein digestion; and absorption. The most down-regulated biological processes were type I interferon signaling, regulation of neuron differentiation and extracellular matrix organization. Our results suggested that the etiology of ALS-PDC is due to metabolic disorders that shifted microglia to a more proinflammatory M1 state instead of a non-inflammatory, repairing M2 state, which exacerbated inflammation and reduced extracellular matrix strength. Supplementation of transforming growth factor beta to ALS/PDC affected organoids increased the expression of interferon-induced transmembrane proteins (IFITMs) and restored M2 microglia populations and extracellular matrix organization. Organoids containing networks of neurons, astrocytes, microglia derived from iPSC with our protocol provides an excellent cellular model for neurodegenerative disease modeling.

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