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Sökning: L773:1547 3287 OR L773:1557 8534

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1.
  • Concepcion Cruz-Santos, Maria, et al. (författare)
  • The Role of microRNAs in Animal Cell Reprogramming
  • 2016
  • Ingår i: Stem Cells and Development. - 1547-3287 .- 1557-8534. ; 25:14, s. 1035-1049
  • Forskningsöversikt (refereegranskat)abstract
    • Our concept of cell reprogramming and cell plasticity has evolved since John Gurdon transferred the nucleus of a completely differentiated cell into an enucleated Xenopus laevis egg, thereby generating embryos that developed into tadpoles. More recently, induced expression of transcription factors, oct4, sox2, klf4, and c-myc has evidenced the plasticity of the genome to change the expression program and cell phenotype by driving differentiated cells to the pluripotent state. Beyond these milestone achievements, research in artificial cell reprogramming has been focused on other molecules that are different than transcription factors. Among the candidate molecules, microRNAs (miRNAs) stand out due to their potential to control the levels of proteins that are involved in cellular processes such as self-renewal, proliferation, and differentiation. Here, we review the role of miRNAs in the maintenance and differentiation of mesenchymal stem cells, epimorphic regeneration, and somatic cell reprogramming to induced pluripotent stem cells.
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2.
  • Dahlin, Joakim S., et al. (författare)
  • Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice
  • 2015
  • Ingår i: Stem Cells and Development. - 1547-3287 .- 1557-8534. ; 24:14, s. 1703-1711
  • Tidskriftsartikel (refereegranskat)abstract
    • Mast cells originate from the bone marrow and develop into c-kit(+) FcRI(+) cells. Both mast cell progenitors (MCp) and mature mast cells express these cell surface markers, and ways validated to distinguish between the two maturation forms with flow cytometry have been lacking. Here, we show that primary peritoneal MCp from naive mice expressed high levels of integrin 7 and had a low side scatter (SSC) light profile; whereas mature mast cells expressed lower levels of integrin 7 and had a high SSC light profile. The maturation statuses of the cells were confirmed using three main strategies: (1) MCp, but not mature mast cells, were shown to be depleted by sublethal whole-body -irradiation. (2) The MCp were small and immature in terms of granule formation, whereas the mature mast cells were larger and had fully developed metachromatic granules. (3) The MCp had fewer transcripts of mast cell-specific proteases and the enzyme responsible for sulfation of heparin than mature mast cells. Moreover, isolated peritoneal MCp gave rise to mast cells when cultured in vitro. To summarize, we have defined MCp and mature mast cells in naive mice by flow cytometry. Using this strategy, mast cell maturation can be studied in vivo.
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3.
  • Hertegård, Stellan, et al. (författare)
  • Hyaluronan Hydrogels for the Local Delivery of Mesenchymal Stromal Cells to the Injured Vocal Fold
  • 2019
  • Ingår i: Stem Cells and Development. - : MARY ANN LIEBERT, INC. - 1547-3287 .- 1557-8534. ; 28:17, s. 1177-1190
  • Tidskriftsartikel (refereegranskat)abstract
    • Mesenchymal stromal cells (MSCs) promote wound healing by expediting the inflammatory phase. Local injection of MSCs into injured vocal folds (VFs) is effective in animal models, suggesting suitability for clinical translation. Despite their therapeutic potential, MSCs do not persist within the VF. This study evaluates whether hyaluronan (HA) hydrogels offer a safe delivery vehicle for local injection of MSCs into VFs, and increase longevity of the cells within the injured tissue. MSCs +/- HA hydrogel were exposed to interleukin (IL)1 beta, IL8, and chemokine (C-C motif) ligand 4, and evaluated for mRNA expression of matrix remodeling genes and secretion of immunomodulatory/prohealing factors. Chemotaxis/invasion in response to inflammation was evaluated. A lapin model of VF injury evaluated in vivo effects of MSCs +/- HA hydrogel on enhancing VF healing. Histological evaluation of inflammation, type I collagen expression, HA hydrogel resorption, and MSC persistence was evaluated at 3 and 25 days after injury. MSCs within HA hydrogel were responsive to their extracellular environment, upregulating immunomodulatory factors when exposed to inflammation. Despite delayed migration out of the gel in vitro, the MSCs did not persist longer within the injured tissue in vivo. MSCs +/- HA hydrogel exerted equivalent dampening of inflammation in vivo. The gel was resorbed within 25 days and no edema was evident. HA hydrogels can be safely used in the delivery of MSCs to injured VFs, minimizing leakage of administered cells. MSCs within the HA hydrogel did not persist longer than those in suspension, but did exert comparable therapeutic effects.
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4.
  • Hoeber, Jan, 1986-, et al. (författare)
  • A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord
  • 2017
  • Ingår i: Stem Cells and Development. - 1547-3287 .- 1557-8534. ; 26:14, s. 1065-1077
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along "bridges" formed by migrating stem cells. Coimplantation of MesoMIM prevented stem cell migration, "bridges" were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular "bridges" in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient alternative way to induce sensory axon regeneration, and (3) a combinatorial approach of individually beneficial components is not necessarily additive, but can be counterproductive for axonal growth.
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5.
  • Jensen, Pernille Linnert, et al. (författare)
  • Proteomic Analysis of Human Blastocoel Fluid and Blastocyst Cells
  • 2013
  • Ingår i: Stem Cells and Development. - 1547-3287 .- 1557-8534. ; 22:7, s. 1126-1135
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the blastocyst and can differentiate into any cell type in the human body. These cells hold a great potential for regenerative medicine, but in order to obtain enough cells needed for medical treatment, culture is required on a large scale. In the undifferentiated state, hESCs appear to possess an unlimited potential for proliferation but optimal, defined and safe culture conditions remains a challenge. The aim of the present study was to identify proteins in the natural environment of undifferentiated hESCs, namely the blastocoel fluid, which is in contact with all the cells in the blastocyst, including hESCs. Fifty-three surplus human blastocysts were donated after informed consent and blastocoel fluid was isolated by micromanipulation. Using highly sensitive nano high pressure liquid chromatography tandem mass spectrometry, 286 proteins were identified in the blastocoel fluid and 1307 proteins in the corresponding cells of the blastocyst. Forty-two were previously uncharacterized proteins - eight of these originated from the blastocoel fluid. Furthermore, several heat shock proteins (Hsp27, Hsp60, Hsc70 and Hsp90) were identified in blastocoel fluid together with zona pellucida proteins (ZP2-4), Vitamin D binding protein and Retinol binding protein. Proteins that regulate ciliary assembly and function were also identified, including Bardet-biedl syndrome protein 7. This study has identified numerous proteins which cells from the ICM of the human blastocyst are exposed to via the blastocoel fluid. These results can be an inspiration for the development of improved culture conditions for hESCs.
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6.
  • Junkunlo, Kingkamon, et al. (författare)
  • PDGF/VEGF-related receptor affects transglutaminase activity to control cell migration during crustacean hematopoiesis
  • 2017
  • Ingår i: Stem Cells and Development. - 1547-3287 .- 1557-8534. ; 26:20, s. 1449-1459
  • Tidskriftsartikel (refereegranskat)abstract
    • The platelet-derived growth factor (PDGF) receptor, a tyrosine kinase (TK) receptor whose ligand is PDGF, is crucial in the transduction of extracellular signals into cells and mediates numerous processes, such as cell proliferation, differentiation, survival, and migration. We demonstrate the important roles of a receptor TK related to the PDGF/VEGF family protein (PVR) in controlling hematopoietic progenitor cell migration by affecting extracellular transglutaminase (TGase) activity. Pl_PVR1, GenBank accession No. KY444650, is highly expressed in hemocytes and the hematopoietic tissue (HPT). Sunitinib malate was used to block the PVF/PVR downstream pathway in HPT cell culture. The addition of Sunitinib also caused the HPT cells to increase in size and begin spreading. An increase in extracellular TGase activity on the HPT cell membrane was observed in a dose-dependent manner after treatment with Sunitinib malate. The presence of crude Ast1 provided a combinatorial beneficial effect that enhanced the number of spreading cells after inhibition of the Pl_PVR downstream signaling cascade. In addition, an increased immunoreactivity for beta-tubulin and elongation of beta-tubulin filaments were found in Pl_PVR signaling-inhibited cells. The potential roles of PVF/PVR signaling in controlling progenitor cell activity during hematopoiesis in crayfish were investigated and discussed.
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7.
  • Kashyap, Vasundhra, et al. (författare)
  • Regulation of Stem Cell Pluripotency and Differentiation Involves a Mutual Regulatory Circuit of the Nanog, OCT4, and SOX2 Pluripotency Transcription Factors With Polycomb Repressive Complexes and Stem Cell microRNAs
  • 2009
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert, Inc.. - 1557-8534 .- 1547-3287. ; 18:7, s. 1093-1108
  • Forskningsöversikt (refereegranskat)abstract
    • Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce transcriptional noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies.
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8.
  • Kingham, Paul J, et al. (författare)
  • Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair
  • 2014
  • Ingår i: Stem Cells and Development. - 1547-3287 .- 1557-8534. ; 23:7, s. 741-754
  • Tidskriftsartikel (refereegranskat)abstract
    • In future, adipose-derived stem cells (ASC) might be used to treat neurological disorders. In this study, the neurotrophic and angiogenic properties of human ASC were evaluated, and their effects in a peripheral nerve injury model were determined. In vitro growth factor stimulation of the cells resulted in increased secretion of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor-A (VEGF-A), and angiopoietin-1 proteins. Conditioned medium from stimulated cells increased neurite outgrowth of dorsal root ganglia (DRG) neurons. Similarly, stimulated cells showed an enhanced ability to induce capillary-like tube formation in an in vitro angiogenesis assay. ASC were seeded into a fibrin conduit that was used to bridge a 10 mm rat nerve gap. After 2 weeks, the animals treated with control or stimulated ASC showed an enhanced axon regeneration distance. Stimulated cells evoked more total axon growth. Analysis of regeneration and apoptosis-related gene expression showed that both ASC and stimulated ASC enhanced GAP-43 and activating transcription factor 3 (ATF-3) expression in the spinal cord and reduced c-jun expression in the DRG. Caspase-3 expression in the DRG was reduced by stimulated ASC. Both ASC and stimulated ASC also increased the vascularity of the fibrin nerve conduits. Thus, ASC produce functional neurotrophic and angiogenic factors, creating a more desirable microenvironment for nerve regeneration.
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9.
  • Kolar, Mallappa K, et al. (författare)
  • The therapeutic effects of human adipose derived stem cells in a rat cervical spinal cord injury model
  • 2014
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 23:14, s. 1659-1674
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinal cord injury triggers a cascade of degenerative changes leading to cell death and cavitation. Severed axons fail to regenerate across the scar tissue and are only capable of limited sprouting. In this study we investigated the effects of adult human adipose derived stem cells (ASC) on axonal regeneration following transplantation into the injured rat cervical spinal cord. ASC did not induce activation of astrocytes in culture and supported neurite outgrowth from adult rat sensory DRG neurons. After transplantation into the lateral funiculus 1mm rostral and caudal to the cervical C3-C4 hemisection, ASC continued to express BDNF, VEGF and FGF-2 for 3 weeks but only in animals treated with cyclosporine A. Transplanted ASC stimulated extensive ingrowth of 5HT-positive raphaespinal axons into the trauma zone with some terminal arborisations reaching the caudal spinal cord. In addition, ASC induced sprouting of raphaespinal terminals in C2 contralateral ventral horn and C6 ventral horn on both sides. Transplanted cells also changed the structure of the lesion scar with numerous astrocytic processes extended into the middle of the trauma zone in a chain-like pattern and in close association with regenerating axons. The density of the astrocytic network was also significantly decreased. Although the transplanted cells had no effect on the density of capillaries around the lesion site, the activity of OX42-positive microglial cells was markedly reduced. However, ASC did not support recovery of forelimb function. The results suggest that transplanted ASC can modify the structure of the glial scar and stimulate axonal sprouting.
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10.
  • König, Julia, 1983-, et al. (författare)
  • Amnion-derived mesenchymal stromal cells show angiogenic properties but resist differentiation into mature endothelial cells
  • 2012
  • Ingår i: Stem Cells and Development. - Rochelle, USA : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 21:8, s. 1309-1320
  • Tidskriftsartikel (refereegranskat)abstract
    • Mesenchymal stromal cells derived from the human amnion (hAMSC) currently play an important role in stem cell research, as they are multipotent cells that can be isolated using noninvasive methods and are immunologically tolerated in vivo. The objective of this study was to evaluate their endothelial differentiation potential with regard to a possible therapeutic use in vascular diseases. hAMSC were isolated from human term placentas and cultured in Dulbecco's modified Eagle's medium (DMEM) (non-induced hAMSC) or endothelial growth medium (EGM-2) (induced hAMSC). Induced hAMSC changed their fibroblast-like toward an endothelial-like morphology, and were able to take up acetylated low-density lipoprotein and form endothelial-like networks in the Matrigel assay. However, they did not express the mature endothelial cell markers von Willebrand factor and vascular endothelial-cadherin. Gene expression analysis revealed that induced hAMSC significantly downregulated pro-angiogenic genes such as tenascin C, Tie-2, vascular endothelial growth factor A (VEGF-A), CD146, and fibroblast growth factor 2 (FGF-2), whereas they significantly upregulated anti-angiogenic genes such as serpinF1, sprouty1, and angioarrestin. Analysis of protein expression confirmed the downregulation of FGF-2 and Tie-2 (27%±8% and 13%±1% of non-induced cells, respectively) and upregulation of the anti-angiogenic protein endostatin (226%±4%). Conditioned media collected from hAMSC enhanced viability of endothelial cells and had a stabilizing effect on endothelial network formation as shown by lactate dehydrogenase and Matrigel assay, respectively. In summary, endothelial induced hAMSC acquired some angiogenic properties but resisted undergoing a complete differentiation into mature endothelial cells by upregulation of anti-angiogenic factors. Nevertheless, they had a survival-enhancing effect on endothelial cells that might be useful in a variety of cell therapy or tissue-engineering approaches.
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  • Resultat 1-10 av 78
  • [1]234567...8Nästa

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