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Navaneetha Santhanam, Lee Kumanchik, Xiufang Guo, Frank Sommerhage, Yunqing Cai, Max Jackson, Candace Martin, George Saad, Christopher W McAleer, Ying Wang, Andrea Lavado, Christopher J Long, James J Hickman
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units...
February 27, 2018: Biomaterials
Peter Stacey, Anne Mai Wassermann, Laura Kammonen, Emma Impey, Anna Wilbrey, Darren Cawkill
Screening against a disease-relevant phenotype to identify compounds that change the outcome of biological pathways, rather than just the activity of specific targets, offers an alternative approach to find modulators of disease characteristics. However, in pain research, use of in vitro phenotypic screens has been impeded by the challenge of sourcing relevant neuronal cell types in sufficient quantity and developing functional end-point measurements with a direct disease link. To overcome these hurdles, we have generated human induced pluripotent stem cell (hiPSC)-derived sensory neurons at a robust production scale using the concept of cryopreserved "near-assay-ready" cells to decouple complex cell production from assay development and screening...
March 1, 2018: SLAS Discovery
Fedir N Kiskin, C-Hong Chang, Christopher J Z Huang, Baraa Kwieder, Christine Cheung, Benjamin J Dunmore, Felipe Serrano, Sanjay Sinha, Nicholas W Morrell, Amer A Rana
No abstract text is available yet for this article.
March 16, 2018: American Journal of Respiratory and Critical Care Medicine
Junya Kitadani, Toshiyasu Ojima, Hiromitsu Iwamoto, Hirotaka Tabata, Mikihito Nakamori, Masaki Nakamura, Keiji Hayata, Masahiro Katsuda, Masayasu Miyajima, Hiroki Yamaue
Clinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model...
March 15, 2018: Scientific Reports
Meixiang Zhang, Justine Ngo, Filomena Pirozzi, Ying-Pu Sun, Anthony Wynshaw-Boris
BACKGROUND: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages...
March 15, 2018: Stem Cell Research & Therapy
Alan D Marmorstein, Adiv A Johnson, Lori A Bachman, Cynthia Andrews-Pfannkoch, Travis Knudsen, Benjamin J Gilles, Matthew Hill, Jarel K Gandhi, Lihua Y Marmorstein, Jose S Pulido
Autosomal recessive bestrophinopathy (ARB) is caused by mutations in the gene BEST1 which encodes bestrophin 1 (Best1), an anion channel expressed in retinal pigment epithelial (RPE) cells. It has been hypothesized that ARB represents the human null phenotype for BEST1 and that this occurs due to nonsense mediated decay (NMD). To test this hypothesis, we generated induced pluripotent stem cells (iPSCs) from a patient with ARB and her parents. After differentiation to retinal pigment epithelial (iPSC-RPE) cells, both BEST1 mRNA and Best1 protein expression were compared to controls...
March 14, 2018: Scientific Reports
Vahid Serpooshan, Sara Sheibani, Pooja Pushparaj, Michal Wojcik, Albert Y Jang, Michelle R Santoso, Joyce H Jang, Haina Huang, Reihaneh Safavi-Sohi, Niloofar Haghjoo, Hossein Nejadnik, Haniyeh Aghaverdi, Hojatollah Vali, Joseph Matthew Kinsella, John Presley, Ke Xu, Phillip Chung-Ming Yang, Morteza Mahmoudi
Cellular uptake of nanoparticles (NPs) depends on the nature of the nanobio system including the solid nanocomponents ( e. g., physicochemical properties of NPs), nanobio interfaces ( e. g., protein corona composition), and the cellular characteristics ( e. g., cell type). In this study, we document the role of sex in cellular uptake of NPs as an "overlooked" factor in nanobio interface investigations. We demonstrate that cell sex leads to differences in NP uptake between male and female human amniotic stem cells (hAMSCs), with greater uptake by female cells...
March 14, 2018: ACS Nano
Melissa Lo Monaco, Greet Merckx, Jessica Ratajczak, Pascal Gervois, Petra Hilkens, Peter Clegg, Annelies Bronckaers, Jean-Michel Vandeweerd, Ivo Lambrichts
Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles...
2018: Stem Cells International
Junhao Deng, Yiling Zhang, Yong Xie, Licheng Zhang, Peifu Tang
Spinal cord injury (SCI) is an intractable and worldwide difficult medical challenge with limited treatments. Neural stem/progenitor cell (NS/PC) transplantation derived from fetal tissues or embryonic stem cells (ESCs) has demonstrated therapeutic effects via replacement of lost neurons and severed axons and creation of permissive microenvironment to promote repair of spinal cord and axon regeneration but causes ethnical concerns and immunological rejections as well. Thus, the implementation of induced pluripotent stem cells (iPSCs), which can be generated from adult somatic cells and differentiated into NS/PCs, provides an effective alternation in the treatment of SCI...
2018: Stem Cells International
Naoki Yahata, Yuji Matsumoto, Minoru Omi, Naoki Yamamoto, Ryuji Hata
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
March 13, 2018: Scientific Reports
Wasco Wruck, James Adjaye
Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs) differentiated into hepatocyte-like cells (HLCs) provide a defined and renewable source of cells for drug screening, toxicology and regenerative medicine. We previously reprogrammed human fetal foreskin fibroblast cells (HFF1) into iPSCs employing an episomal plasmid-based integration-free approach, this iPSC-line and the hESC lines H1 and H9 were used to model hepatogenesis in vitro. Biochemical characterisation confirmed glycogen storage, ICG uptake and release, urea and bile acid production, as well as CYP3A4 activity...
March 13, 2018: Scientific Data
Ashfaqul Hoque, Priyadharshini Sivakumaran, Simon T Bond, Naomi X Y Ling, Anne M Kong, John W Scott, Nadeeka Bandara, Damián Hernández, Guei-Sheung Liu, Raymond C B Wong, Michael T Ryan, Derek J Hausenloy, Bruce E Kemp, Jonathan S Oakhill, Brian G Drew, Alice Pébay, Shiang Y Lim
Human induced pluripotent stem cells (iPSCs) are a valuable tool for studying the cardiac developmental process in vitro, and cardiomyocytes derived from iPSCs are a putative cell source for personalized medicine. Changes in mitochondrial morphology have been shown to occur during cellular reprogramming and pluripotent stem cell differentiation. However, the relationships between mitochondrial dynamics and cardiac mesoderm commitment of iPSCs remain unclear. Here we demonstrate that changes in mitochondrial morphology from a small granular fragmented phenotype in pluripotent stem cells to a filamentous reticular elongated network in differentiated cardiomyocytes are required for cardiac mesodermal differentiation...
December 2018: Cell Death Discovery
Yangyang Ma, Tong Yu, Yuanxing Cai, Huayan Wang
Derivation of bona fide porcine pluripotent stem cells is still a critical issue because porcine embryonic stem cells (ESCs) are not available yet, and most of the culture conditions to maintain porcine induced pluripotent stem cells (piPSCs) are based on conditions for mouse and human iPS cells. In this study, we generated a doxycycline-inducible porcine iPS cell line (DOX-iPSCs) and used it to screen the optimal culture condition to sustain the self-renewal of piPSCs. We found that LIF and b-FGF were required for porcine cell reprogramming, but were not essential cytokines for maintaining the self-renewal and pluripotency of piPSCs...
December 2018: Cell Death Discovery
Huan Yi, Bingbing Xie, Ben Liu, Xuan Wang, Li Xu, Jia Liu, Min Li, Xiufeng Zhong, Fuhua Peng
Induced pluripotent stem cells (iPSCs) have provided new opportunities for motor neuron disease (MND) modeling, drug screening, and cellular therapeutic development. Among the various types of iPSCs, urine-derived iPSCs have become a promising source of stem cells because they can be safely and noninvasively isolated and easily reprogrammed. Here, for the first time, we differentiated urine-derived iPSCs (urine-iPSCs) into motor neurons (MNs) and compared the capacity of urine-iPSCs and cord-blood-derived iPSCs (B-iPSCs) to differentiate into MNs...
2018: Stem Cells International
Ginetta Collo, Laura Cavalleri, Federica Bono, Cristina Mora, Stefania Fedele, Roberto William Invernizzi, Massimo Gennarelli, Giovanna Piovani, Tilo Kunath, Mark J Millan, Emilio Merlo Pich, PierFranco Spano
The antiparkinsonian ropinirole and pramipexole are D3 receptor- (D3R-) preferring dopaminergic (DA) agonists used as adjunctive therapeutics for the treatment resistant depression (TRD). While the exact antidepressant mechanism of action remains uncertain, a role for D3R in the restoration of impaired neuroplasticity occurring in TRD has been proposed. Since D3R agonists are highly expressed on DA neurons in humans, we studied the effect of ropinirole and pramipexole on structural plasticity using a translational model of human-inducible pluripotent stem cells (hiPSCs)...
2018: Neural Plasticity
Sucharita Boddu, Peter W Hashim, John K Nia, Rebecca Horowitz, Aaron Farberg, Gary Goldenberg
Stem cell therapies are at the forefront of regenerative aesthetic medicine. Multipotent stem cells and induced pluripotent stem cells (iPSCs), progenitor cells that result from the dedifferentiation of specialized adult cells, have demonstrated promise in tissue regeneration for a wide range of dermatologic conditions and aesthetic applications. Herein, we review the potential of stem cells as a new frontier in aesthetic dermatology.
January 2018: Cutis; Cutaneous Medicine for the Practitioner
Wen-Li Deng, Mei-Ling Gao, Xin-Lan Lei, Ji-Neng Lv, Huan Zhao, Kai-Wen He, Xi-Xi Xia, Ling-Yun Li, Yu-Chen Chen, Yan-Ping Li, Deng Pan, Tian Xue, Zi-Bing Jin
Retinitis pigmentosa (RP) is an irreversible, inherited retinopathy in which early-onset nyctalopia is observed. Despite the genetic heterogeneity of RP, RPGR mutations are the most common causes of this disease. Here, we generated induced pluripotent stem cells (iPSCs) from three RP patients with different frameshift mutations in the RPGR gene, which were then differentiated into retinal pigment epithelium (RPE) cells and well-structured retinal organoids possessing electrophysiological properties. We observed significant defects in photoreceptor in terms of morphology, localization, transcriptional profiling, and electrophysiological activity...
February 28, 2018: Stem Cell Reports
Hai-Qin Huo, Zhuang-Yin Qu, Fang Yuan, Lixiang Ma, Lin Yao, Min Xu, Yao Hu, Jing Ji, Anita Bhattacharyya, Su-Chun Zhang, Yan Liu
The brain of Down syndrome (DS) patients exhibits fewer interneurons in the cerebral cortex, but its underlying mechanism remains unknown. By morphometric analysis of cortical interneurons generated from DS and euploid induced pluripotent stem cells (iPSCs), we found that DS GABA neurons are smaller and with fewer neuronal processes. The proportion of calretinin over calbindin GABA neurons is reduced, and the neuronal migration capacity is decreased. Such phenotypes were replicated following transplantation of the DS GABAergic progenitors into the mouse medial septum...
February 28, 2018: Stem Cell Reports
Maxime W C Rousseaux, Tyler Tschumperlin, Hsiang-Chih Lu, Elizabeth P Lackey, Vitaliy V Bondar, Ying-Wooi Wan, Qiumin Tan, Carolyn J Adamski, Jillian Friedrich, Kirk Twaroski, Weili Chen, Jakub Tolar, Christine Henzler, Ajay Sharma, Aleksandar Bajić, Tao Lin, Lisa Duvick, Zhandong Liu, Roy V Sillitoe, Huda Y Zoghbi, Harry T Orr
Polyglutamine (polyQ) diseases are caused by expansion of translated CAG repeats in distinct genes leading to altered protein function. In spinocerebellar ataxia type 1 (SCA1), a gain of function of polyQ-expanded ataxin-1 (ATXN1) contributes to cerebellar pathology. The extent to which cerebellar toxicity depends on its cognate partner capicua (CIC), versus other interactors, remains unclear. It is also not established whether loss of the ATXN1-CIC complex in the cerebellum contributes to disease pathogenesis...
March 7, 2018: Neuron
Noriomi Eguchi, Ichiro Sora, Keiko Muguruma
Human brain development has generally been studied through the analysis of postmortem tissues because of limited access to fetal brain tissues. This approach, however, only provides information from the perspective of long-term development. To investigate the pathophysiology of neurodevelopmental disorders, it is necessary to understand the detailed mechanisms of human brain development. Recent advances in pluripotent stem cell (PSC) technologies enable us to establish in vitro brain models from human induced PSCs (hiPSCs), which can be used to examine the pathophysiological mechanisms of neurodevelopmental disorders...
March 7, 2018: Biochemical and Biophysical Research Communications
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