scholarly journals Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold

2019 ◽  
Vol 10 ◽  
pp. 127-133 ◽  
Author(s):  
Takahito Minami ◽  
Takamichi Ishii ◽  
Kentaro Yasuchika ◽  
Ken Fukumitsu ◽  
Satoshi Ogiso ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Artificial Liver ◽  
Induced Pluripotent ◽  
Decellularized Liver

scholarly journals Modeling Herpes Simplex Virus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem Cells

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Leonardo D’Aiuto ◽  
David C. Bloom ◽  
Jennifer N. Naciri ◽  
Adam Smith ◽  
Terri G. Edwards ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Two Dimensional ◽  
Herpes Simplex Virus 1 ◽  
Cns Neurons ◽  
Induced Pluripotent ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTHerpes simplex virus 1 (HSV-1) establishes latency in both peripheral nerve ganglia and the central nervous system (CNS). The outcomes of acute and latent infections in these different anatomic sites appear to be distinct. It is becoming clear that many of the existing culture models using animal primary neurons to investigate HSV-1 infection of the CNS are limited and not ideal, and most do not recapitulate features of CNS neurons. Human induced pluripotent stem cells (hiPSCs) and neurons derived from them are documented as tools to study aspects of neuropathogenesis, but few have focused on modeling infections of the CNS. Here, we characterize functional two-dimensional (2D) CNS-like neuron cultures and three-dimensional (3D) brain organoids made from hiPSCs to model HSV-1–human–CNS interactions. Our results show that (i) hiPSC-derived CNS neurons are permissive for HSV-1 infection; (ii) a quiescent state exhibiting key landmarks of HSV-1 latency described in animal models can be established in hiPSC-derived CNS neurons; (iii) the complex laminar structure of the organoids can be efficiently infected with HSV, with virus being transported from the periphery to the central layers of the organoid; and (iv) the organoids support reactivation of HSV-1, albeit less efficiently than 2D cultures. Collectively, our results indicate that hiPSC-derived neuronal platforms, especially 3D organoids, offer an extraordinary opportunity for modeling the interaction of HSV-1 with the complex cellular and architectural structure of the human CNS.IMPORTANCEThis study employed human induced pluripotent stem cells (hiPSCs) to model acute and latent HSV-1 infections in two-dimensional (2D) and three-dimensional (3D) CNS neuronal cultures. We successfully established acute HSV-1 infections and infections showing features of latency. HSV-1 infection of the 3D organoids was able to spread from the outer surface of the organoid and was transported to the interior lamina, providing a model to study HSV-1 trafficking through complex neuronal tissue structures. HSV-1 could be reactivated in both culture systems; though, in contrast to 2D cultures, it appeared to be more difficult to reactivate HSV-1 in 3D cultures, potentially paralleling the low efficiency of HSV-1 reactivation in the CNS of animal models. The reactivation events were accompanied by dramatic neuronal morphological changes and cell-cell fusion. Together, our results provide substantive evidence of the suitability of hiPSC-based neuronal platforms to model HSV-1–CNS interactions in a human context.

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

Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells

2015 ◽  
Vol 11 (3) ◽  
pp. 926-935 ◽  
Author(s):  
Hyoe Komae ◽  
Hidekazu Sekine ◽  
Izumi Dobashi ◽  
Katsuhisa Matsuura ◽  
Minoru Ono ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Induced Pluripotent

scholarly journals Hepatic spheroids derived from human induced pluripotent stem cells in bio-artificial liver rescue porcine acute liver failure

Cell Research ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 95-97 ◽  
Author(s):  
Sitong Chen ◽  
Jinglin Wang ◽  
Haozhen Ren ◽  
Yinan Liu ◽  
Chengang Xiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Artificial Liver ◽  
Induced Pluripotent

scholarly journals Efficient Differentiation of Mouse Induced Pluripotent Stem Cells into Alveolar Epithelium Type II with a BRD4 Inhibitor

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Toru Momozane ◽  
Eriko Fukui ◽  
Soichiro Funaki ◽  
Makoto Fujii ◽  
Yuhei Kinehara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Protein C ◽  
Three Dimensional ◽  
Alveolar Epithelium ◽  
Type Ii ◽  
Differentiation Induction ◽  
Induced Pluripotent ◽  
Differentiation Efficiency

Regenerative medicine has continued to progress for lung biology and lung diseases. Efforts have focused on a variety of different applications for pluripotent stem cells. Several groups have reported successful methods for inducing differentiation of induced pluripotent stem cells (iPSCs) into the airway epithelium such as alveolar epithelium type II (ATII). However, differentiation efficiency varies among reports and improvements are needed. In the present paper, we propose a novel method for elimination of residual undifferentiated murine iPSCs using JQ1, a potent inhibitor of bromodomain (BRD) and extraterminal domain (BET) family proteins, for efficient differentiation into ATII. First, the murine iPSC line 20D-17 was induced to differentiate into ATII over a period of 26 days (days 0-26) using previously reported embryoid body seeding and stepwise differentiation methods. mRNA expressions of differentiation markers including surfactant protein C (Sftpc) were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) results, and 17% of the cells were shown positive for prosurfactant protein C (proSPC) in flow cytometry analysis. Next, those cells were cultured three-dimensionally in Matrigel for an additional 14 days (days 26-40), during which JQ1 was added for 4 days (days 28-32) to remove residual undifferentiated iPSCs. As a result, on day 40, the mRNA expression level of Sftpc in the three-dimensional culture was maintained at the same level as on day 26 and shown to be further increased by the addition of JQ1, with 39% of the cells found to express proSPC, showing that differentiation efficiency could be further increased. Three-dimensional culture with BRD4 inhibition by JQ1 improved the differentiation induction efficiency to ATII by removing residual undifferentiated murine iPSCs during the differentiation induction process.

scholarly journals Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells

2015 ◽  
Vol 35 (12) ◽  
pp. 2677-2685 ◽  
Author(s):  
Xin Yi Chan ◽  
Rebecca Black ◽  
Kayla Dickerman ◽  
Joseph Federico ◽  
Mathieu Lévesque ◽  
...  
Keyword(s):  
Stem Cells ◽  
Diabetic Patient ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Vascular Network ◽  
Induced Pluripotent

scholarly journals Opportunities and challenges for the use of induced pluripotent stem cells in modelling neurodegenerative disease

Open Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 180177 ◽  
Author(s):  
Yi-Ying Wu ◽  
Feng-Lan Chiu ◽  
Chan-Shien Yeh ◽  
Hung-Chih Kuo
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Disease Patient ◽  
Neuronal Cultures ◽  
Sporadic Disease ◽  
Induced Pluripotent ◽  
Human Ipsc

Adult-onset neurodegenerative diseases are among the most difficult human health conditions to model for drug development. Most genetic or toxin-induced cell and animal models cannot faithfully recapitulate pathology in disease-relevant cells, making it excessively challenging to explore the potential mechanisms underlying sporadic disease. Patient-derived induced pluripotent stem cells (iPSCs) can be differentiated into disease-relevant neurons, providing an unparalleled platform for in vitro modelling and development of therapeutic strategies. Here, we review recent progress in generating Alzheimer's, Parkinson's and Huntington's disease models from patient-derived iPSCs. We also describe novel discoveries of pathological mechanisms and drug evaluations that have used these patient iPSC-derived neuronal models. Additionally, current human iPSC technology allows researchers to model diseases with 3D brain organoids, which are more representative of tissue architecture than traditional neuronal cultures. We discuss remaining challenges and emerging opportunities for the use of three-dimensional brain organoids in modelling brain development and neurodegeneration.

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