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Stem Cells and Development

Souichiro Nakamae, Yukiko Toba, Kazuo Takayama, Fuminori Sakurai, Hiroyuki Mizuguchi
Human induced pluripotent stem cell-derived hepatocyte-like cells (HLCs) are expected to be utilized in pharmaceutical research, including drug screening. However, the hepatocyte functions of the HLCs are still lower than those of human hepatocytes. Therefore, we attempted to improve the hepatocyte differentiation method by modulating the DNA epigenetic status. We first examined the expression profiles of the maintenance DNA methyltransferase (DNMT) 1 and the de novo DNMTs DNMT3A and DNMT3B, all of which are essential for mammalian development...
February 27, 2018: Stem Cells and Development
Evi Luyckx, Wendy Van Leuven, Daniel Andre, Alessandra Quarta, Kristien Reekmans, Erik Fransen, Luc Moens, Thomas Hankeln, Peter Ponsaerts, Sylvia Dewilde
In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngbfl -)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (NgbKO -)NSC line. NgbKO -NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upregulation of Cdk6, both enhancing the cell cycle...
February 27, 2018: Stem Cells and Development
Panicos Shangaris, Stavros P Loukogeorgakis, Michael Blundell, Eleni Petra, Steven W Shaw, Durrgah Ramachandra, Panagiotis Maghsoudlou, Luca Urbani, Adrian Thrasher, Anna L David, Paolo De Coppi
Clinical success of in utero transplantation (IUT) using allogeneic hematopoietic stem cells (HSCs) has been limited to fetuses that lack an immune response to allogeneic cells due to severe immunological defects, and where transplanted genetically normal cells have a proliferative or survival advantage. Amniotic fluid (AF) is an autologous source of stem cells with hematopoietic potential that could be used to treat congenital blood disorders. We compared the ability of congenic and allogeneic mouse AF stem cells (AFSC) to engraft the hematopoietic system of time-mated C57BL/6J mice (E13...
February 26, 2018: Stem Cells and Development
Zhou Tan, Jingya Li, Xuejing Zhang, Xueqin Yang, Zunyi Zhang, Ke-Jie Yin, Huarong Huang
TP53 is a widely studied tumor suppressor gene that controls various cellular functions including cell differentiation. However, little is known about its functional roles in smooth muscle cell (SMC) differentiation from embryonic stem cells (ESCs). SMC differentiation is at the heart of our understanding of vascular development, normal blood pressure homeostasis and the pathogenesis of vascular diseases such as atherosclerosis, hypertension, restenosis, as well as aneurysm. Using retinoid acid (RA)-induced SMC differentiation models, we observed that p53 expression is increased during in vitro differentiation of mouse ESCs into SMCs...
February 26, 2018: Stem Cells and Development
Oliver Petters, Christian Schmidt, Ralf Henkelmann, Philipp Pieroh, Gero Hütter, Bastian Marquaß, Gabriela Aust, Ronny Maik Schulz
Due to the limited self-healing capacity of articular cartilage, innovative, regenerative approaches are of particular interest. The use of two-stage procedures utilizing in vitro expanded mesenchymal stromal cells (MSCs) from various cell sources requires good manufacturing practice-compliant production, a process with high demands on time, staffing and financial resources. In contrast, one- stage procedures are directly available but need a safe enrichment of potent MSCs. CD271 is a surface marker known to marking the majority of native MSCs in bone marrow...
February 26, 2018: Stem Cells and Development
Qian Gao, Wenhao Zhang, Lifang Ma, Xu Li, Haisong Wang, Yanni Li, Remo Freimann, Yang Yu, Ling Shuai, Anton Wutz
Haploid cells facilitate genetic screening of recessive mutations for a single set of chromosomes. Haploid embryonic stem cells (haESCs) have been achieved in several species and widely utilized in genetic screens. The fact that haESCs undergo substantial diploidization during differentiation has limited the screening to other haploid cell types. Here, we report a method to establish haploid neural stem cells (haNSCs) by selection for a Pax6 reporter. We inserted a green fluorescence protein (GFP) marker gene by homologous recombination into the Pax6 locus of a haESC line...
February 22, 2018: Stem Cells and Development
Jung Woo Park, Juan Yang, Ren-He Xu
Paired box protein 6 (PAX6) is a master regulator of the eye development. Over the last past two decades, our understanding of eye development, especially the molecular function of PAX6, has focused on transcriptional control of the Pax6 expression. However, other regulatory mechanisms for gene expression, including alternative splicing (AS), have been understudied in the eye development. Recent findings suggest that two PAX6 isoforms generated by AS of Pax6 pre-mRNA may play previously underappreciated role(s) during eye development, especially, the corneal development...
February 21, 2018: Stem Cells and Development
Lizhen Liu, Qin Yu, Shan Fu, Binsheng Wang, Kaimin Hu, Limengmeng Wang, Yongxian Hu, Yulin Xu, Xiaohong Yu, He Huang
Mobilization of mesenchymal stem cells (MSCs) is an attractive strategy for cell therapy. Our previous study demonstrated that MSCs can be mobilized in circulating blood by short-term hypoxia and hypoxia-inducible factor-1α (HIF-1α) is essential for MSC mobilization. In the present study, the effect of the hypoxia mimicking agent CoCl2 was examined on MSC mobilization. The results indicated that the frequency of circulating MSCs increased slightly by administration of CoCl2. However, the mobilization efficiency was low...
February 13, 2018: Stem Cells and Development
Andrey Ratushnyy, Maria Ezdakova, Danila Yakubets, Ludmila Buravkova
Multipotent mesenchymal stem/stromal cells (MSCs) are strongly involved in tissue homeostasis mainly through paracrine regulation. Here we examined the influence of simulated microgravity on the angiogenic potential of adipose-derived MSCs (ASCs). The conditioned medium (CM) from RPM-exposed ASCs stimulated the formation of vessel network in ovo, endothelial cell (EC) capillary-like network ex ovo and non-directed EC migration in vitro. These effects were driven by alteration of both angiogenesis-related gene and protein expression...
February 12, 2018: Stem Cells and Development
Jan Jakub Lica, Grzegorz Jan Grabe, Mateusz Heldt, Majus Misiak, Patrycja Bloch, Marcin Serocki, Marta Switalska, Joanna Wietrzyk, Maciej Baginski, Andrzej Hellmann, Edward Borowski, Andrzej Skladanowski
Proliferation and expansion of leukemia is driven by Leukemic Stem Cells (LSCs). Multidrug resistance (MDR) of LSCs is one of the main reasons of failure and relapses in Acute Myeloid Leukemia (AML) treatment. Here we show that maintaining HL-60 at low cell culture density or applying a 240-day treatment with anthrapyridazone (BS-121) increased the percentage of primitive cells which include LSCs determining the overall stage profile. This change manifested in: morphology, expression of both cell surface markers and redox-state proteins as well as mitochondrial potential...
February 12, 2018: Stem Cells and Development
Jonathan Baio, Aida F Martinez, Leonard Bailey, Nahidh Hasaniya, Michael J Pecaut, Mary Kearns-Jonker
Spaceflight impacts cardiovascular function in astronauts; however, its impact on cardiac development and the stem cells that form the basis for cardiac repair is unknown. Accordingly, further research is needed to uncover the potential relevance of such changes to human health. Using simulated microgravity (SMG) generated by two-dimensional clinorotation and culture aboard the International Space Station (ISS), we assessed the effects of mechanical unloading on human neonatal cardiovascular progenitor cell (CPC) developmental properties and signaling...
February 12, 2018: Stem Cells and Development
Chunling Xue, Yamei Shen, Xuechun Li, Li Ba, Zhao Sun, Junjie Gu, Yunfei Chen, Baitao Ma, Junji Wei, Qin Han, Robert Chunhua Zhao
Angiogenesis is a complicated and sequential process that plays an important role in different physiological processes. Mesenchymal stem cells (MSCs), which are pluripotent stem cells, are widely used for the treatment of ischemic and traumatic diseases, and exosomes derived from these cells can also promote angiogenesis. Therefore, we aimed to uncover mechanisms to improve MSC exosome-mediated angiogenesis. For this study, we isolated human adipose-derived mesenchymal stem cells (hAD-MSCs) and assessed differentiation ability and markers...
February 7, 2018: Stem Cells and Development
Diana Kim, Vivian Lee, Taylor Dorsey, Laura Niklason, Liqiong Gui, Guohao Dai
Pluripotent stem cell derived endothelial cells (ECs) have great potential to be used in vascular therapy or tissue engineering. It is also much desired to obtain arterial or venous ECs for specific applications. Factors that are critical for the proper arterial or venous differentiation from pluripotent stem cells are still need to be understood. Here, we aim to investigate this problem deeper by examining neuropilin-1 (Nrp1), an early arterial marker that may be critical for arterial cell fate commitment...
February 7, 2018: Stem Cells and Development
Jens Christian Schwamborn
Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. The incidence of PD cases increases with age, accordingly classically PD is considered to be an age associated neurodegenerative disease. In this review the hypothesis that PD is actually a neurodevelopmental disorder that is compensated for long time, will be discussed. However, patients who suffer from Parkinson's disease typically do not show symptoms early in their live. This implies that, if the hypothesis that PD has a significant neurodevelopmental component is correct, the developmental defects are compensated for long time...
February 7, 2018: Stem Cells and Development
Shiva Hamidian Jahromi, Catalina Estrada, Yunqing Li, Elaine Cheng, John E Davies
Intravenously administered mesenchymal stromal cells (MSCs) are rapidly entrapped in the lungs, where they display an anti-inflammatory phenotype. Intramuscular (IM) delivery provides an increased MSC dwell-time, which could result in a sustained modulation of an inflammatory milieu. We studied the therapeutic effects of IM delivered MSCs to treat a distant (contralateral) inflammation, and compared the efficacy of neonatal (umbilical cord) and adult bone marrow (BM) MSCs. Inflammation decreased over 48h but neonatal cells showed an earlier response than BMMSCs...
February 5, 2018: Stem Cells and Development
Alexander Kondrashov, Minh Duc Hoang, James Smith, Jamie Bhagwan, Gary Duncan, Diogo Mosqueira, Maria Munoz, Nguyen T N Vo, Chris Denning
Modelling disease with hPSCs is hindered because the impact on cell phenotype from genetic variability between individuals can be greater than from the pathogenic mutation. While 'footprint-free' Cas9/CRISPR editing solves this issue, existing approaches are inefficient or lengthy. Here, a simplified PiggyBac strategy shortened hPSC editing by 2 weeks and required one round of clonal expansion and genotyping rather than two, with similar efficiencies to the longer conventional process. Success was shown across 4 cardiac-associated loci (ADRB2, GRK5, RYR2, ACTC1) by genomic cleavage and editing efficiencies of 8-93% and 8-67%, respectively, including mono- and/or bi-allelic events...
February 5, 2018: Stem Cells and Development
Scott C Vermilyea, Marina Emborg
Leucine-rich repeat kinase 2 (LRRK2) G2019S (glycine to serine) is the most common mutation associated with sporadic and familial Parkinson's disease (PD) with 80% penetrance by age 70. This mutation is found worldwide, with up to 40% of individuals in the North African Arab population carrying the mutation. Induced pluripotent stem cells (iPSCs) derived from fibroblasts of patients carrying the LRRK2 G2019S mutation have been a critical source of cells for generating dopaminergic neurons and studying G2019S-related pathology...
February 5, 2018: Stem Cells and Development
Qingyun Mai, Xiuyun Mai, Xin Huang, Dan Zhang, Kejun Huang, Canquan Zhou
Human parthenogenetic embryonic stem cells (hPESCs) represent a source of histocompatible tissues for transplantation and carry two copies of the maternally genome, but lack the paternally genome. In this study, we selected 63 known human imprinted genes to investigate the imprinting status of hPESC. The expression level of these genes including 27 maternally and 36 paternally imprinted were illustrated in hPESC and human embryonic stem cells derived from fertilized embryos (hESC) cell lines. The expression activity changes of these genes were analyzed in undifferentiated and early differentiated hPESC cell lines...
February 5, 2018: Stem Cells and Development
Konstantinos E Hatzistergos, Zhijie Jiang, Krystalenia Valasaki, Lauro M Takeuchi, Wayne Balkan, Preethi Atluri, Dieter Saur, Barbara Seidler, Nicholas Tsinoremas, Darcy DiFede, Joshua M Hare
Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiologic function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest progenitors (NCs), we hypothesized that microgravity can impair NC derived cardiac structures. Accordingly, we conducted in vitro simulated microgravity experiments employing NC genetic lineage-tracing in mice with cKitCreERT2/+, Isl1nLacZ and Wnt1-Cre reporter alleles...
January 16, 2018: Stem Cells and Development
Donghui Liu, Nimshitha Pavathuparambil Abdul Manaph, Mohammed Al-Hawwas, Xin-Fu Zhou, Hong Liao
Generation of induced pluripotent stem cells (iPSCs) from other somatic cells has provided great hopes for transplantation therapies. However, these cells still cannot be used for clinical application due to the low reprogramming and differentiation efficiency beside the risk of mutagenesis and tumor formation. Compared to iPSCs, induced neural stem cells (iNSCs) are easier to terminally differentiate into neural cells and safe; thus, iNSCs hold more opportunities than iPSCs to treat neural diseases. On the other hand, recent studies have showed that small molecules (SMs) can dramatically improve the efficiency of reprogramming and SMs alone can even convert one kind of somatic cells into another, which is much safer and more effective than transcription factor-based methods...
March 1, 2018: Stem Cells and Development
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