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https://www.readbyqxmd.com/read/28643455/pathways-governing-development-of-stem-cell-derived-pancreatic-%C3%AE-cells-lessons-from-embryogenesis
#1
Sara Al-Khawaga, Bushra Memon, Alexandra E Butler, Shahrad Taheri, Abdul B Abou-Samra, Essam M Abdelalim
The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies...
June 22, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28641611/-dmso-promotes-hematopoietic-differentiation-of-human-embryonic-stem-cells-in-vitro
#2
Hong-Tao Wang, Meng-Ge Wang, Xin Liu, Pei Su, Lei-Sheng Zhang, Cui-Cui Liu, Yu Wang, Dan Wu, Qian Tu, Jia-Xi Zhou
OBJECTIVE: To explore the role of dimethyl sulfoxide (DMSO) in the hematopoietic differentiation of human embryonic stem cells (hESCs). METHODS: The role of DMSO in hematopoietic differentiation of hESC was investigated by using a established stepwise hematopoietic differentiation system from hESC, immunofluorescouse assay and flow cytometry. Furthermore, the window phase of DMSO action was explored by adding it to the different stage of hematopoietic differentiation...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28636206/retinal-vascular-injuries-and-intravitreal-human-embryonic-stem-cell-derived-haemangioblasts
#3
Jin-Da Wang, Ying An, Jing-Shang Zhang, Xiu-Hua Wan, Wei Zhang, Robert Lanza, Shi-Jiang Lu, Jost B Jonas, Liang Xu
OBJECTIVE: To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion. METHODS: Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion...
June 21, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#4
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627682/microvesicles-released-from-human-embryonic-stem-cell-derived-mesenchymal-stem-cells-inhibit-proliferation-of-leukemia-cells
#5
Yuan Ji, Yongbin Ma, Xiang Chen, Xianyan Ji, Jianyi Gao, Lei Zhang, Kai Ye, Fuhao Qiao, Yao Dai, Hui Wang, Xiangmei Wen, Jiang Lin, Jiabo Hu
Human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSC‑MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC‑MSCs and hESC‑MSC‑MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay...
June 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28626601/long-term-efficacy-of-gmp-grade-xeno-free-hesc-derived-rpe-cells-following-transplantation
#6
Trevor J McGill, Osnat Bohana-Kashtan, Jonathan W Stoddard, Michael D Andrews, Neelay Pandit, Lior R Rosenberg-Belmaker, Ofer Wiser, Limor Matzrafi, Eyal Banin, Benjamin Reubinoff, Nir Netzer, Charles Irving
PURPOSE: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. METHODS: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells...
June 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28626459/the-immunogenicity-and-immune-tolerance-of-pluripotent-stem-cell-derivatives
#7
REVIEW
Xin Liu, Wenjuan Li, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28623610/a-singular-role-of-ik1-promoting-the-development-of-cardiac-automaticity-during-cardiomyocyte-differentiation-by-ik1-induced-activation-of-pacemaker-current
#8
Yu Sun, Valeriy Timofeyev, Adrienne Dennis, Emre Bektik, Xiaoping Wan, Kenneth R Laurita, Isabelle Deschênes, Ronald A Li, Ji-Dong Fu
The inward rectifier potassium current (IK1) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that IK1 could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (If) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of IK1 to activate If and thereby promote automaticity has not been explored. In this study, we combined mathematical and experimental assays and found that only IK1 and If, at a proper-ratio of densities, were sufficient to generate rhythmic MP-oscillations even in unexcitable cells (i...
June 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28614773/assessment-of-neurotoxicity-of-pharmacological-compounds-during-early-neural-development-of-human-embryonic-stem-cells
#9
H Y Kang, E J Hong, H S Kang, C Ahn, E B Jeung
Human embryonic stem cells (hESCs), with the potential for differentiation, have been used to evaluate the embryotoxicity of various compounds. The effects of pharmacological compounds (cytosine arabinoside, 5-fluorouracil, hydroxyurea, indomethacin, and dexamethasone) on neurogenesis of hESCs over 28 days were examined based on cytotoxicity (half-maximal inhibitory concentration of viability, IC50) and expression of neural markers. Cytosine arabinoside, 5-fluorouracil, and hydroxyurea showed strong cytotoxicity (IC50 < 10 μM), whereas indomethacin and dexamethasone had weaker cytotoxic effects...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28610919/neural-differentiation-of-human-embryonic-stem-cells-induced-by-the-transgene-mediated-overexpression-of-single-transcription-factors
#10
Misako Matsushita, Yuhki Nakatake, Itaru Arai, Keiji Ibata, Kazuhisa Kohda, Sravan K Goparaju, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B H Ko, Takanori Kanai, Michisuke Yuzaki, Minoru S H Ko
Pluripotent human embryonic stem cells (hESCs) can differentiate into multiple cell lineages, thus, providing one of the best platforms to study molecular mechanisms during cell differentiation. Recently, we have reported rapid and efficient differentiation of hESCs into functional neurons by introducing a cocktail of synthetic mRNAs encoding five transcription factors (TFs): NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. Here we further tested a possibility that even single transcription factors, when expressed ectopically, can differentiate hESCs into neurons...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28609558/ipsc-technology-based-regenerative-therapy-for-diabetes
#11
REVIEW
Yasushi Kondo, Taro Toyoda, Nobuya Inagaki, Kenji Osafune
The directed differentiation of human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), into pancreatic endocrine lineages has been vigorously examined by reproducing the in vivo developmental processes of pancreas. Recent advances in this research field have enabled the generation from hESCs/iPSCs of functionally mature β-like cells in vitro that show glucose-responsive insulin secretion ability. The therapeutic potentials of hESC/iPSC-derived pancreatic cells have been evaluated using diabetic animal models, and transplantation methods including immunoprotective devices that prevent immune responses from hosts to the implanted pancreatic cells have been investigated towards the development of regenerative therapies against diabetes...
June 13, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28600830/external-beam-radiation-therapy-for-the-treatment-of-human-pluripotent-stem-cell-derived-teratomas
#12
Andrew S Lee, Chad Tang, Wan Xing Hong, Sujin Park, Magdalena Bazalova, Geoff Nelson, Veronica Sanchez-Freire, Isaac Bakerman, Wendy Zhang, Evgenios Neofytou, Andrew J Connolly, Charles K Chan, Edward E Graves, Irving L Weissman, Patricia K Nguyen, Joseph C Wu
Human pluripotent stem cells (hPSCs), including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present the evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by utilizing a microCT irradiator capable of targeted treatment in small animals...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28597690/dna-methylation-and-copy-number-variation-analyses-of-human-embryonic-stem-cell-derived-neuroprogenitors-after-low-dose-decabromodiphenyl-ether-and-or-bisphenol-a-exposure
#13
L Du, W Sun, X M Li, X Y Li, W Liu, D Chen
The polybrominated diphenyl ether flame retardants decabromodiphenyl ether (BDE-209) and bisphenol A (BPA) are environmental contaminants that can cross the placenta and exert toxicity in the developing fetal nervous system. Copy number variants (CNVs) play a role in a number of genetic disorders and may be implicated in BDE-209/BPA teratogenicity. In this study, we found that BDE-209 and/or BPA exposure decreased neural differentiation efficiency of human embryonic stem cells (hESCs), although there was a >90% induction of neuronal progenitor cells (NPCs) from exposed hESCs...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28591651/transplantation-of-human-pancreatic-endoderm-cells-reverses-diabetes-post-transplantation-in-a-prevascularized-subcutaneous-site
#14
Andrew R Pepper, Rena Pawlick, Antonio Bruni, John Wink, Yasmin Rafiei, Doug O'Gorman, Richard Yan-Do, Boris Gala-Lopez, Tatsuya Kin, Patrick E MacDonald, A M James Shapiro
Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of "healthy" human donor pancreata restricts the broader application of this effective curative therapy. "β-Like" cells derived from human embryonic stem cells (hESC), with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs) in a prevascularized subcutaneous site...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28588839/human-embryonic-stem-cell-therapy-for-aplastic-anemia
#15
Geeta Shroff, Rakesh Gupta, Lalduhawmi Zadeng
Human embryonic stem cell (hESC) therapy is the potential therapeutic option for the treatment of patients with aplastic anemia (AA). The study showed a remarkable improvement in the AA patient subsequent to hESC administration. No adverse events occurred in the patient. hESC therapy is safe and effective for AA patients.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28583200/high%C3%A2-quality-clinical%C3%A2-grade-human-embryonic-stem-cell-lines-derived-from-fresh-discarded-embryos
#16
Jinpei Ye, Nicola Bates, Despina Soteriou, Lisa Grady, Clare Edmond, Alex Ross, Alan Kerby, Philip A Lewis, Tope Adeniyi, Ronnie Wright, Kay V Poulton, Marcus Lowe, Susan J Kimber, Daniel R Brison
BACKGROUND: Human embryonic stem cells (hESCs) hold tremendous promise for cell replacement therapies for a range of degenerative diseases. In order to provide cost-effective treatments affordable by public health systems, HLA-matched allogeneic tissue banks of the highest quality clinical-grade hESCs will be required. However only a small number of existing hESC lines are suitable for clinical use; they are limited by moral and ethical concerns and none of them apply Good Manufacturing Practice (GMP) standards to the earliest and critical stages of gamete and embryo procurement...
June 5, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28582519/x-chromosome-inactivation-in-human-pluripotent-stem-cells-as-a-model-for-human-development-back-to-the-drawing-board
#17
Mieke Geens, Susana M Chuva De Sousa Lopes
BACKGROUND: Human pluripotent stem cells (hPSC), both embryonic and induced (hESC and hiPSC), are regarded as a valuable in vitro model for early human development. In order to fulfil this promise, it is important that these cells mimic as closely as possible the in vivo molecular events, both at the genetic and epigenetic level. One of the most important epigenetic events during early human development is X chromosome inactivation (XCI), the transcriptional silencing of one of the two X chromosomes in female cells...
June 5, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28579405/human-embryo-research-in-belgium-an-overview
#18
Guido Pennings, Seppe Segers, Sophie Debrock, Björn Heindryckx, Velichka Kontozova-Deutsch, Usha Punjabi, Hilde Vande Velde, André van Steirteghem, Heidi Mertes
OBJECTIVE: To present an overview of the numbers and types of human embryos used in research projects in Belgium from 2007 to 2015. DESIGN: Analysis of all research proposals approved by the Federal Commission for Medical and Scientific Research on Embryos In Vitro. SETTING: Not applicable. PATIENT(S): Not applicable. MAIN OUTCOME MEASURE(S): Number of embryos used for research, number of embryos created for research, and areas of embryo research...
June 1, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28579391/a-rho-small-gtpase-regulator-abr-secures-mitotic-fidelity-in-human-embryonic-stem-cells
#19
Masatoshi Ohgushi, Maki Minaguchi, Mototsugu Eiraku, Yoshiki Sasai
Pluripotent stem cells can undergo repeated self-renewal while retaining genetic integrity, but they occasionally acquire aneuploidy during long-term culture, which is a practical obstacle for medical applications of human pluripotent stem cells. In this study, we explored the biological roles of ABR, a regulator of RHO family small GTPases, and found that it has pivotal roles during mitotic processes in human embryonic stem cells (hESCs). Although ABR has been shown to be involved in dissociation-induced hESC apoptosis, it does not appear to have direct effects on cell survival unless cell-cell contact is impaired...
May 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28565767/hair-follicle-derived-mesenchymal-cells-support-undifferentiated-growth-of-embryonic-stem-cells
#20
Vanessa Carvalho Coelho de Oliveira, Danúbia Silva Dos Santos, Leandro Vairo, Tais Hanae Kasai Brunswick, Luiz Alberto Soares Pimentel, Adriana Bastos Carvalho, Antonio Carlos Campos de Carvalho, Regina Coeli Dos Santos Goldenberg
The aim of the present study was to investigate whether feeder layers composed of human hair follicle-derived mesenchymal stem cells (hHFDCs) are able to support human embryonic stem cells (hESCs). hHFDCs and mouse embryonic fibroblasts (MEFs) were isolated and cultured in Dulbecco's modified Eagle's medium (DMEM)/F-12 and low-glucose DMEM, respectively. hHFDCs were passaged three times and subsequently characterized. hHFDCs and MEFs were mitotically inactivated with mitomycin C for 3 h prior to co-culture with H9-hESCs...
May 2017: Experimental and Therapeutic Medicine
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