Article
Biochemistry & Molecular Biology
Akshay Narkar, James M. Willard, Ksenia Blinova
Summary: This review focuses on recent advances in chronic cardiotoxicity assessment using cardiomyocytes differentiated from human induced pluripotent stem cells. The review summarizes studies on chronic cardiotoxicity induced by various drugs, including anticancer agents, antibiotics, anti-HCV drugs, and antidiabetic drugs. The review also highlights the use of hiPSC-CMs in investigating the chronic effects of non-pharmaceutical cardiotoxicants and the development of biomarker assays. The comprehensive investigation of long-term repeated exposure-induced effects on cardiomyocytes can provide mechanistic insights and recapitulate drug and environmental cardiotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Keyang Zhu, Xiaoming Bao, Yingchao Wang, Ting Lu, Ling Zhang
Summary: Cardiovascular disease (CVD) is the leading cause of death worldwide. Natural compounds extracted from medicinal plants, known for their diverse biological activities and low toxicity, are becoming more popular in the search for new drugs. However, the use of immortalized cell lines or animal models for preclinical evaluation of natural products has limitations in accurately recapitulating pathogenic phenotypes and translating to clinical relevance. The development of human induced pluripotent stem cell (hiPSC) technology combined with efficient cardiomyocyte differentiation methods provides an ideal platform for modeling human cardiomyopathies in vitro. Screening of drugs, especially natural products, based on these models has shown promise in recapitulating important physiological properties.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Engineering, Biomedical
Niall J. Treacy, Shane Clerkin, Jessica L. Davis, Ciaran Kennedy, Aline F. Miller, Alberto Saiani, Jacek K. Wychowaniec, Dermot F. Brougham, John Crean
Summary: Human induced pluripotent stem cell (hiPSC)-derived kidney organoids were matured within synthetic self-assembling peptide hydrogels (SAPHs) of variable stiffness. The organoids exhibited complex structures comparable to those differentiated within animal-derived matrix, Matrigel. Differentiation within a higher stiffness SAPH generated podocytes with more mature gene expression profiles. Maturing the organoids within a 3D microenvironment significantly reduced off-target cell types.
BIOACTIVE MATERIALS
(2023)
Article
Pharmacology & Pharmacy
C. Altrocchi, K. Van Ammel, M. Steemans, M. Kreir, F. Tekle, A. Teisman, D. J. Gallacher, H. R. Lu
Summary: This study developed an in vitro screening platform using human-induced pluripotent stem cell-derived cardiomyocytes to evaluate both acute and delayed electrophysiological and cytotoxic effects of reference compounds, which can contribute to the early assessment of drug-induced cardiotoxicity.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
William P. Bozza, Kazuyo Takeda, Wei-Lun Alterovitz, Chao-Kai Chou, Rong-Fong Shen, Baolin Zhang
Summary: Anthracyclines are effective chemotherapy drugs but their clinical use is limited by dose-dependent cardiotoxicity. This study used hiPSC-CMs and impedance measurement to monitor cardiomyocyte responses, comparing four structurally similar anthracycline drugs with different cardiotoxicity profiles. Results showed that differences in cardiotoxicity were linked to cardiomyocyte uptake and activation/inhibition of multiple cellular pathways.
Article
Neurosciences
Ari Ogaki, Yuji Ikegaya, Ryuta Koyama
Summary: Researchers have developed a method to efficiently transplant human induced pluripotent stem cell-derived microglia (hiPSC-MG) into mouse hippocampal slice cultures, achieving a high replacement rate. The transplanted microglia changed their morphology and phagocytosed cell debris when neuronal death was induced. This method provides a useful ex vivo tool for evaluating the properties of hiPSC-MG.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Tine Tricot, Catherine M. Verfaillie, Manoj Kumar
Summary: The pharmaceutical industry requires efficient and relevant in vitro liver models for drug discovery. Human induced pluripotent stem cells (hiPSCs) offer a new opportunity for liver disease modeling and drug discovery. However, the differentiation of iPSCs into fully mature liver cells remains challenging.
Review
Biochemistry & Molecular Biology
Yang Li, Xia Yang, Richie Plummer, Yoshihito Hayashi, Xiao-Shan Deng, Yun-Zhong Nie, Hideki Taniguchi
Summary: Liver disease is a global health issue, and organ transplantation is the only effective therapy but is hindered by donor shortage. Human pluripotent stem cells (hPSCs) are used for studying liver biology and pathology, developing alternative therapies. hPSCs can differentiate into multiple cell types for generating models to investigate and replicate biological activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Pia Montanucci, Teresa Pescara, Alessia Greco, Giuseppe Basta, Riccardo Calafiore
Summary: This study explores the potential application and research of functional beta islet-like cells derived from hiPSCs in treating type 1 diabetes. A microencapsulation system using human elastin-like recombinamers (ELRs) was tested to envelope hiPSCs, and in vitro and in vivo characterization showed that ELRs did not interfere with the viability, function, and other biological properties of the differentiated hiPSCs. Preliminary in vivo studies also indicated that ELRs may provide immunoprotection to the cell grafts.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Engineering, Biomedical
Gyunggyu Lee, Hyemin Kim, Ji Young Park, Gyeongmin Kim, Jiyou Han, Seok Chung, Ji Hun Yang, Jang Su Jeon, Dong-Hun Woo, Choongseong Han, Sang Kyum Kim, Han-Jin Park, Jong-Hoon Kim
Summary: Advances in pluripotent stem cell technology have led to the efficient and reproducible generation of hepatocyte-like cell spheroids in various sizes using microwell culture platforms. These spheroids show high expressions of hepatic marker genes, enhanced drug-metabolizing activity, and increased sensitivity to hepatotoxicants compared to traditional hepatocytes. This imaging-based toxicity screening system holds promise for predicting drug-induced hepatotoxicity in the early stages of drug discovery.
Review
Biochemistry & Molecular Biology
Qiulin Luo, Nan Wang, Hanyun Que, Erziya Mai, Yanting Hu, Rui Tan, Jian Gu, Puyang Gong
Summary: The development of regenerative medicine has brought new possibilities for treating end-stage liver diseases. Stem cells, particularly induced pluripotent stem cells (iPSCs), have shown potential as a reliable source for generating hepatocyte-like cells (HLCs) due to their unlimited multiplication capacity and ability to simulate human disease. However, efficiently and accurately inducing iPSCs to differentiate into HLCs remains a hot topic. This review discusses the methods, challenges, and parameters involved in inducing iPSC differentiation, as well as the application of iPSCs in drug screening and modeling of liver disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cell Biology
Michael E. Baumgartner, Eugenia Piddini
Summary: Human induced pluripotent stem cells (hIPSCs) are an important tool, but challenges remain in optimizing their use due to cell competition between wild-type and variant cells leading to contamination and genetic aberrations.
DEVELOPMENTAL CELL
(2021)
Article
Cell Biology
Marwa Hussein, Mattia Pasqua, Ulysse Pereira, Nassima Benzoubir, Jean-Charles Duclos-Vallee, Anne Dubart-Kupperschmitt, Cecile Legallais, Antonietta Messina
Summary: This article introduces a method that combines three-dimensional culture techniques to differentiate functional hepatocytes from human induced pluripotent stem cells (hiPSCs), and demonstrates that this method can generate mature and functional hepatocytes for liver tissue engineering and bioartificial liver applications.
Article
Multidisciplinary Sciences
Chia-Lung Wu, Amanda Dicks, Nancy Steward, Ruhang Tang, Dakota B. Katz, Yun-Rak Choi, Farshid Guilak
Summary: The study identified key genes such as WNT and MITF in off-target cell differentiation during chondrogenic differentiation using bulk and single cell RNA-sequencing; inhibiting these pathways can enhance cell homogeneity and yield.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Marco Romano, Raul Elgueta, Daniel McCluskey, Ana Maria Ortega-Prieto, Emilie Stolarczyk, Francesco Dazzi, Baltasar Lucendo-Villarin, Jose Meseguer-Ripolles, James Williams, Giorgia Fanelli, David C. Hay, Fiona M. Watt, Giovanna Lombardi
Summary: Regenerative medicine aims to replace damaged tissues by stimulating tissue repair or transplanting cells. Pluripotent stem cells have the potential for unlimited cell production, making them valuable for regenerative medicine. However, immune responses pose a challenge to success. This study investigates the immunological properties of human pluripotent stem cell-derived hepatocyte-like cells and shows their potential for in vitro immunoregulation.
Article
Biochemistry & Molecular Biology
Mostafa Kiamehr, Alexa Klettner, Elisabeth Richert, Ali Koskela, Arto Koistinen, Heli Skottman, Kai Kaarniranta, Katriina Aalto-Setala, Kati Juuti-Uusitalo
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Mostafa Kiamehr, Laura Heiskanen, Thomas Laufer, Aneta Duesterloh, Mustafa Kahraman, Reijo Kakela, Reijo Laaksonen, Katriina Aalto-Setala
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Cell Biology
Disheet Shah, Laura Virtanen, Chandra Prajapati, Mostafa Kiamehr, Josef Gullmets, Gun West, Joose Kreutzer, Mari Pekkanen-Mattila, Tiina Helio, Pasi Kallio, Pekka Taimen, Katriina Aalto-Setala
Article
Cell Biology
Disheet Shah, Chandra Prajapati, Kirsi Penttinen, Reeja Maria Cherian, Jussi T. Koivumaki, Anna Alexanova, Jari Hyttinen, Katriina Aalto-Setala
Article
Biochemistry & Molecular Biology
Iris D. Zelnik, Giora Volpert, Leena E. Viiri, Dimple Kauhanen, Tamar Arazi, Katriina Aalto-Setala, Reijo Laaksonen, Anthony H. Futerman
JOURNAL OF LIPID RESEARCH
(2020)
Article
Oncology
Saara Marttila, Leena E. Viiri, Pashupati P. Mishra, Brigitte Kuhnel, Pamela R. Matias-Garcia, Leo-Pekka Lyytikainen, Tiina Ceder, Nina Mononen, Wolfgang Rathmann, Juliane Winkelmann, Annette Peters, Mika Kahonen, Nina Hutri-Kahonen, Markus Juonala, Katriina Aalto-Setala, Olli Raitakari, Terho Lehtimaki, Melanie Waldenberger, Emma Raitoharju
Summary: The study found that the methylation status of the nc886 epiallele is mostly binomial and is associated with the mother's age and socioeconomic status. Once established, this methylation status remains stable for at least 25 years. It is strongly linked to the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines, as well as with glucose and insulin levels during adolescence, but not with adult glucose metabolism indicators or the incidence of type 2 diabetes.
CLINICAL EPIGENETICS
(2021)
Article
Engineering, Biomedical
M. Lehti-Polojarvi, M. J. Rasanen, L. E. Viiri, H. Vuorenpaa, S. Miettinen, A. Seppanen, J. Hyttinen
Summary: A novel multimodal imaging technique combining R-mfEIT and OPT was proposed to accurately extract the conductivity spectrum of tissue engineered specimens, demonstrating the ability to distinguish between different tissue states and detect the presence of stem cells. This technique is expected to be a valuable tool for monitoring the growth and viability of tissue engineered specimens in vitro.
PHYSICS IN MEDICINE AND BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Leena E. Viiri, Tommi Rantapero, Mostafa Kiamehr, Anna Alexanova, Mikko Oittinen, Keijo Viiri, Henri Niskanen, Matti Nykter, Minna U. Kaikkonen, Katriina Aalto-Setala
SCIENTIFIC REPORTS
(2019)
Article
Cell Biology
Mostafa Kiamehr, Leena E. Viiri, Terhi Vihervaara, Kaisa M. Koistinen, Mika Hilvo, Kim Ekroos, Reijo Kakela, Katriina Aalto-Setala
DISEASE MODELS & MECHANISMS
(2017)