Stem Cells Dev. 2015 Mar 31. [Epub ahead of print]

Pig Induced Pluripotent Stem Cell Derived Neural Rosettes Developmentally Mimic Human Pluripotent Stem Cell Neural Differentiation

Gallegos-Cardenas A1, Webb RL, Jordan ET, West RC, West FD, Yang JY, Wang K, Stice SL

Abstract

For diseases of the brain, the pig (Sus scrofa) is increasingly being used as a model organism that shares many anatomical and biological similarities with humans. We report that pig induced pluripotent stem cells (iPSC) can recapitulate events in early mammalian neural development. Pig iPSC line (POU5F1high/SSEA4low) had a higher potential to form neural rosettes (NR) containing neuroepithelial cells than either POU5F1low/SSEA4low or POU5F1low/SSEA4high lines. Thus, POU5F1 and SSEA4 pluripotency marker profiles in starting porcine iPSC populations can predict their propensity to form more robust NR populations in culture. The NR were isolated and expanded in vitro, retaining their NR morphology and neuroepithelial molecular properties. These cells expressed anterior central nervous system fate markers OTX2 and GBX2 through at least seven passages, and responded to retinoic acid, promoting a more posterior fate (HOXB4+, OTX2- and GBX2-). These findings offer insight into pig iPSC development, which parallels the human iPSC in both anterior and posterior neural cell fates. ...

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BMC Neurosci. 2008 Dec 11;9:118. doi: 10.1186/1471-2202-9-118.

Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology.

Hurst JH1, Mumaw J, Machacek DW, Sturkie C, Callihan P, Stice SL, Hooks SB.

Abstract

BACKGROUND: Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP) cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. RESULTS: Our results demonstrate that Lysophosphatidic Acid (LPA) and Sphingosine-1-phosphate (S1P) receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown ...

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ASN Neuro. 2014 Nov 24;6(6). pii: 1759091414558416. doi: 10.1177/1759091414558416. Print 2014.

Convergent regulation of neuronal differentiation and Erk and Akt kinases in human neural progenitor cells by lysophosphatidic acid, sphingosine 1-phosphate, and LIF: specific roles for the LPA1 receptor.

Callihan P, Ali MW, Salazar H, Quach N, Wu X, Stice SL, Hooks SB.

Abstract

The bioactive lysophospholipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) have diverse effects on the developing nervous system and neural progenitors, but the molecular basis for their pleiotropic effects is poorly understood. We previously defined LPA and S1P signaling in proliferating human neural progenitor (hNP) cells, and the current study investigates their role in neuronal differentiation of these cells. Differentiation in the presence of LPA or S1P significantly enhanced cell survival and decreased expression of neuronal markers. Further, the LPA receptor antagonist Ki16425 fully blocked the effects of LPA, and differentiation in the presence of Ki16425 dramatically enhanced neurite length. LPA and S1P robustly activated Erk, but surprisingly both strongly suppressed Akt activation. Ki16425 and pertussis toxin blocked LPA activation of Erk but not LPA inhibition of Akt, suggesting distinct receptor and G-protein subtypes mediate these effects. Finally, we explored cross talk between ...

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Cell Reprogram. 2014 Oct;16(5):366-78. doi: 10.1089/cell.2014.0028. Epub 2014 Aug 1.

Nonviral minicircle generation of induced pluripotent stem cells compatible with production of chimeric chickens

Yu P, Lu Y, Jordan BJ, Liu Y, Yang JY, Hutcheson JM, Ethridge CL, Mumaw JL, Kinder HA, Beckstead RB, Stice SL, West FD.

Abstract

Abstract Chickens are vitally important in numerous countries as a primary food source and a major component of economic development. Efforts have been made to produce transgenic birds through pluripotent stem cell [primordial germ cells and embryonic stem cells (ESCs)] approaches to create animals with improved traits, such as meat and egg production or even disease resistance. However, these cell types have significant limitations because they are hard to culture long term while maintaining developmental plasticity. Induced pluripotent stem cells (iPSCs) are a novel class of stem cells that have proven to be robust, leading to the successful development of transgenic mice, rats, quail, and pigs and may potentially overcome the limitations of previous pluripotent stem cell systems in chickens. In this study we generated chicken (c) iPSCs from fibroblast cells for the first time using a nonviral minicircle reprogramming approach...

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Stem Cells Dev. 2014 Apr 10

Induced Pluripotency in Chicken Embryonic Fibroblast Results in a Germ Cell Fate

Lu Y, West FD, Jordan BJ, Jordan ET, West RC, Yu P, He Y, Barrios MA, Zhu Z, Petitte JN, Beckstead RB, Stice SL.

Abstract

Germ cells are critically important as the vehicle that passes genetic information from one generation to the next. Correct development of these cells is essential and perturbation in their development often leads to reproductive failure and disease. Despite the importance of germ cells, little is known about the mechanisms underlying the acquisition and maintenance of the germ cell character. Using a reprogramming strategy, we demonstrate that over-expression of ectopic transcription factors in embryonic fibroblast can lead to the generation of chicken induced-PGCs (ciPGCs). These ciPGCs express pluripotent markers POU5F1, SSEA1 and the germ cell defining proteins CVH and DAZL, closely resembling in vivo sourced PGCs instead of embryonic stem cells (ESCs). Moreover, CXCR4 expressing ciPGCs were capable of migrating to the embryonic gonad after injection into the vasculature of stage 15 embryos, indicating the acquisition of a germ cell fate in these cells....

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Experimental & Translational Stroke Medicine 23;6 (1) (March): 5-18

Development and Characterization of a Yucatan Miniature Biomedical Pig Permanent Middle Cerebral Artery Occlusion Stroke Model

Platt SR, Holmes SP, Howerth EW, Duberstein KJ, Dove CR, Kinder HA, Wyatt EL, Linville AV, Lau VW, Stice SL, Hill WD, Hess DC, West F

Abstract

BACKGROUND: Efforts to develop stroke treatments have met with limited success despite an intense need to produce novel treatments. The failed translation of many of these therapies in clinical trials has lead to a close examination of the therapeutic development process. One of the major factors believed to be limiting effective screening of these treatments is the absence of an animal model more predictive of human responses to treatments. The pig may potentially fill this gap with a gyrencephalic brain that is larger in size with a more similar gray-white matter composition to humans than traditional stroke animal models. In this study we develop and characterize a novel pig middle cerebral artery occlusion (MCAO) ischemic stroke model.

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Physiol Behav. 2014 Feb 10

Gait analysis in a pre- and post-ischemic stroke biomedical pig model

Duberstein KJ, Platt SR, Holmes SP, Dove CR, Howerth EW, Kent M, Stice SL, Hill WD, Hess DC, West FD

Abstract

Severity of neural injury including stroke in human patients, as well as recovery from injury, can be assessed through changes in gait patterns of affected individuals. Similar quantification of motor function deficits has been measured in rodent animal models of such injuries. However, due to differences in fundamental structure of human and rodent brains, there is a need to develop a large animal model to facilitate treatment development for neurological conditions. Porcine brain structure is similar to that of humans, and therefore the pig may make a more clinically relevant animal model. The current study was undertaken to determine key gait characteristics in normal biomedical miniature pigs and dynamic changes that occur post-neural injury in a porcine middle cerebral artery (MCA) occlusion ischemic stroke model...

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Stem Cell Res. 2013 Jul

Inhibition of DNA methyltransferases and histone deacetylases induces astrocytic differentiation of neural progenitors

Majumder A, Dhara SK, Swetenburg R, Mithani M, Cao K, Medrzycki M, Fan Y, Stice SL

Abstract

Understanding how to specify rapid differentiation of human neural progenitor towards enriched non-transformed human astrocyte progenitors will provide a critical cell source to further our understanding of how astrocytes play a pivotal role in neural function and development. Human neural progenitors derived from pluripotent embryonic stem cells and propagated in adherent serum-free cultures provide a fate restricted renewable source for quick production of neural cells; however, such cells are highly refractive to astrocytogenesis and show a strong neurogenic bias, similar to neural progenitors from the early embryonic central nervous system (CNS). We found that several astrocytic genes are hypermethylated in such progenitors potentially preventing generation of astrocytes and leading to the proneuronal fate of these progenitors...

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Birth Defects Res B Dev Reprod Toxicol. 2013 Jun

Ethanol alters proliferation and differentiation of normal and chromosomally abnormal human embryonic stem cell-derived neurospheres

Krishnamoorthy M, Gerwe BA, Scharer CD, Sahasranaman V, Eilertson CD, Nash RJ, Usta SN, Kelly S, Rose M, Peraza R, Arumugham J, Stewart B, Stice SL, Nash RJ

Abstract

Ethanol is a powerful substance and, when consumed during pregnancy, has significant psychoactive and developmental effects on the developing fetus. These abnormalities include growth retardation, neurological deficits, and behavioral and cognitive deficiencies, commonly referred to as fetal alcohol spectrum disorder. The effect of ethanol has been reported to affect cellular development on the embryonic level, however, not much is known about mutations contributing to the influence of ethanol. The purpose of our study was to determine if mutation contribute to changes in differentiation patterning, cell-cycle regulatory gene expression, and DNA methylation in human embryonic stem cells after ethanol exposure...

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1985 - 2016

NCBI Collection

Stice SL

My NCBI collections

View my collection, "slstice@era commons's My Bibliography" from NCBI

Cell Reprogram. 2013 Apr

Galactosyltransferase knockout pig induced pluripotent stem cells: a cell source for the production of xenotransplant pigs

Liu Y, Yang JY, Lu Y, Yu P, Dove CR, Hutcheson JM, Mumaw JL, Stice SL, West FD

Abstract

The shortage of human organs and tissues for transplant has led to significant interest in xenotransplantation of pig tissues for human patients. However, transplantation of pig organs results in an acute immune rejection, leading to death of the organ within minutes. The α-1,3-galactosyltransferase (GALT) gene has been knocked out in pigs to reduce rejection, yet additional genes need to be modified to ultimately make pig tissue immunocompatible with humans...

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Am J Physiol Cell Physiol. 2013 Feb 15

A novel in vitro model system for smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells

Guo X, Stice SL, Boyd NL, Chen SY

Abstract

The objective of this study was to develop a novel in vitro model for smooth muscle cell (SMC) differentiation from human embryonic stem cell-derived mesenchymal cells (hES-MCs). We found that hES-MCs were differentiated to SMCs by transforming growth factor-β (TGF-β) in a dose- and time-dependent manner as demonstrated by the expression of SMC-specific genes smooth muscle α-actin, calponin, and smooth muscle myosin heavy chain...

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Stem Cells. 2012 Nov

Neurotrophic effects of leukemia inhibitory factor on neural cells derived from human embryonic stem cells

Majumder A, Banerjee S, Harrill JA, Machacek DW, Mohamad O, Bacanamwo M, Mundy WR, Wei L, Dhara SK, Stice SL

Abstract

Various growth factor cocktails have been used to proliferate and then differentiate human neural progenitor (NP) cells derived from embryonic stem cells (ESC) for in vitro and in vivo studies. However, the cytokine leukemia inhibitory factor (LIF) has been largely overlooked. Here, we demonstrate that LIF significantly enhanced in vitro survival and promoted differentiation of human ESC-derived NP cells. In NP cells, as well as NP-derived neurons, LIF reduced caspase-mediated apoptosis and reduced both spontaneous and H2O2-induced reactive oxygen species in culture. In vitro, NP cell proliferation and the yield of differentiated neurons were significantly higher in the presence of LIF. In NP cells, LIF enhanced cMyc phosphorylation, commonly associated with self-renewal/proliferation...

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Stem Cells Dev. 2012 Sep

Lectins identify glycan biomarkers on glioblastoma-derived cancer stem cells

Tucker-Burden C, Chappa P, Krishnamoorthy M, Gerwe BA, Scharer CD, Heimburg-Molinaro J, Harris W, Usta SN, Eilertson CD, Hadjipanayis CG, Stice SL, Brat DJ, Nash RJ

Abstract

Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. Despite aggressive therapy with surgery, radiotherapy, and chemotherapy, nearly all patients succumb to disease within 2 years. Several studies have supported the presence of stem-like cells in brain tumor cultures that are CD133-positive, are capable of self-renewal, and give rise to all cell types found within the tumor, potentially perpetuating growth. CD133 is a widely accepted marker for glioma-derived cancer stem cells; however, its reliability has been questioned, creating a need for other identifiers of this biologically important subpopulation. We used a panel of 20 lectins to identify differences in glycan expression found in the glycocalyx of undifferentiated glioma-derived stem cells and differentiated cells that arise from them. Fluorescently labeled lectins that specifically recognize α-N-acetylgalactosamine (GalNAc) and α-N-acetylglucosamine (GlcNAc) differentially bound to the cell surface based on the state of cellular differentiation. GalNAc and GlcNAc were highly expressed on the surface of undifferentiated cells and showed markedly reduced expression over a 12-day duration of differentiation...

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Toxicol Sci. 2012 Sep

Metabolomic response of human embryonic stem cell-derived germ-like cells after exposure to steroid hormones

West FD, Henderson WM, Yu P, Yang JY, Stice SL, Smith MA

Abstract

To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC exposure. Human embryonic stem cells can differentiate into numerous functional cell types including germ-like cells (GLCs)...

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Stem Cells Dev. 2012 Feb 10

Avian-induced pluripotent stem cells derived using human reprogramming factors

Lu Y, West FD, Jordan BJ, Mumaw JL, Jordan ET, Gallegos-Cardenas A, Beckstead RB, Stice SL

Abstract

To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC exposure. Human embryonic stem cells can differentiate into numerous functional cell types including germ-like cells (GLCs)...

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Int J Biomater. 2012;2012:861794

Rapid Heterotrophic Ossification with Cryopreserved Poly(ethylene glycol-) Microencapsulated BMP2-Expressing MSCs

Mumaw J, Jordan ET, Sonnet C, Olabisi RM, Olmsted-Davis EA, Davis AR, Peroni JF, West JL, West F, Lu Y, Stice SL

Abstract

Autologous bone grafting is the most effective treatment for long-bone nonunions, but it poses considerable risks to donors, necessitating the development of alternative therapeutics. Poly(ethylene glycol) (PEG) microencapsulation and BMP2 transgene delivery are being developed together to induce rapid bone formation...

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