| 1. |
- Abomaray, F, et al.
(författare)
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Mesenchymal Stromal Cells Are More Immunosuppressive In Vitro If They Are Derived from Endometriotic Lesions than from Eutopic Endometrium
- 2017
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2017, s. 3215962-
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Tidskriftsartikel (refereegranskat)abstract
- Endometriosis is an inflammatory disease with predominance of immunosuppressive M2 macrophages in the pelvic cavity that could be involved in the pathology through support and immune escape of ectopic lesions. Mesenchymal stromal cells (MSC) are found in ectopic lesions, and MSC from nonendometriosis sources are known to induce M2 macrophages. Therefore, MSC were hypothesized to play a role in the pathology of endometriosis. The aim was to characterize the functional phenotype of MSC in ectopic and eutopic endometrium from women with endometriosis. Stromal cells from endometriotic ovarian cysts (ESCcyst) and endometrium (ESCendo) were examined if they exhibited a MSC phenotype. Then, ESC were phenotypically examined for protein and gene expression of immunosuppressive and immunostimulatory molecules. Finally, ESC were functionally examined for their effects on monocyte differentiation into macrophages. ESCcystand ESCendoexpressed MSC markers, formed colonies, and differentiated into osteoblasts and adipocytes. Phenotypically, ESCcystwere more immunosuppressive, with significantly higher expression of immunosuppressive molecules. Functionally, ESCcystinduced more spindle-shaped macrophages, with significantly higher expression of CD14 and CD163, both features of M2 macrophages. The results suggest that ESCcystmay be more immunosuppressive than ESCendoand may promote immunosuppressive M2 macrophages that may support growth and reduce immunosurveillance of ectopic lesions.
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| 2. |
- Abomaray, F, et al.
(författare)
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Mesenchymal Stromal Cells Support Endometriotic Stromal Cells In Vitro
- 2018
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2018, s. 7318513-
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Tidskriftsartikel (refereegranskat)abstract
- Endometriosis is an inflammatory disease marked by ectopic growth of endometrial cells. Mesenchymal stromal cells (MSC) have immunosuppressive properties that have been suggested as a treatment for inflammatory diseases. Therefore, the aim herein was to examine effects of allogeneic MSC on endometriosis-derived cellsin vitroas a potential therapy for endometriosis. MSC from allogeneic adipose tissue (Ad-MSC) and stromal cells from endometrium (ESCendo) and endometriotic ovarian cysts (ESCcyst) from women with endometriosis were isolated. The effects of Ad-MSC on ESCendoand ESCcystwere investigated usingin vitroproliferation, apoptosis, adhesion, tube formation, migration, and invasion assays. Ad-MSC significantly increased proliferation of ESC compared to untreated controls. Moreover, Ad-MSC significantly decreased apoptosis and increased survival of ESC. Ad-MSC significantly increased adhesion of ESCendoand not ESCcyston fibronectin. Conditioned medium from cocultures of Ad-MSC and ESC significantly increased tube formation of human umbilical vein endothelial cells on matrigel. Ad-MSC may significantly increase migration of ESCcystand did not increase invasion of both cell types. The data suggest that allogeneic Ad-MSC should not be considered as a potential therapy for endometriosis, because they may support the pathology by maintaining and increasing growth of ectopic endometrial tissue.
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| 3. |
- Abomaray, FM, et al.
(författare)
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Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells from Decidua Basalis of Human Term Placenta
- 2016
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2016, s. 5184601-
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cell (MSC) therapies for the treatment of diseases associated with inflammation and oxidative stress employ primarily bone marrow MSCs (BMMSCs) and other MSC types such as MSC from the chorionic villi of human term placentae (pMSCs). These MSCs are not derived from microenvironments associated with inflammation and oxidative stress, unlike MSCs from thedecidua basalisof the human term placenta (DBMSCs). DBMSCs were isolated and then extensively characterized. Differentiation of DBMSCs into three mesenchymal lineages (adipocytes, osteocytes, and chondrocytes) was performed. Real-time polymerase chain reaction (PCR) and flow cytometry techniques were also used to characterize the gene and protein expression profiles of DBMSCs, respectively. In addition, sandwich enzyme-linked immunosorbent assay (ELISA) was performed to detect proteins secreted by DBMSCs. Finally, the migration and proliferation abilities of DBMSCs were also determined. DBMSCs were positive for MSC markers and HLA-ABC. DBMSCs were negative for hematopoietic and endothelial markers, costimulatory molecules, and HLA-DR. Functionally, DBMSCs differentiated into three mesenchymal lineages, proliferated, and migrated in response to a number of stimuli. Most importantly, these cells express and secrete a distinct combination of cytokines, growth factors, and immune molecules that reflect their unique microenvironment. Therefore, DBMSCs could be attractive, alternative candidates for MSC-based therapies that treat diseases associated with inflammation and oxidative stress.
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| 4. |
- Aguila, JC, et al.
(författare)
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Cellular programming and reprogramming: sculpting cell fate for the production of dopamine neurons for cell therapy
- 2012
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-9678 .- 1687-966X. ; 2012, s. 412040-
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Tidskriftsartikel (refereegranskat)abstract
- Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be appliedin vitroto induce, select, and reprogram cells to the mesostriatal dopamine fate.
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| 5. |
- Akhmanova, M, et al.
(författare)
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Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research
- 2015
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2015, s. 167025-
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems.
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| 6. |
- Albalushi, H, et al.
(författare)
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Laminin 521 Stabilizes the Pluripotency Expression Pattern of Human Embryonic Stem Cells Initially Derived on Feeder Cells
- 2018
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Ingår i: Stem cells international. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2018, s. 7127042-
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem (hES) cells represent an important tool to study early cell development. The previously described use of human recombinant laminin (LN) 521 represented a step forward in generating clinically safe culture conditions. To test the short-term effect of LN521 on cultured hES cells, five male hES cell lines were cultured on human foreskin fibroblasts (hFFs), Matrigel, LN521, and LN121 and characterized by qPCR, immunofluorescence analysis, as well as their potential for three-germ layer differentiation. Variations in gene expression related to pluripotency, stemness, and testicular cells at different passages and culture conditions were evaluated by qPCR. All cell lines expressed pluripotency markers at protein and RNA level and were able to differentiate into cell types of the three germ layers after being cultured on LN521 for nine passages. Reduction in variation of pluripotency marker expression could be observed after culturing the cells on LN521 for nine passages. hES cells cultured on LN521 exhibited less differentiation, faster cell growth, and attachment when compared to hES cells cultured on LN121 or Matrigel. Our results indicate a positive effect of LN521 in stabilizing pluripotency gene expression and might be the first step towards more controllable and robust culture conditions for hES cells.
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| 7. |
- Avaliani, Natalia, et al.
(författare)
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Directly Converted Human Fibroblasts Mature to Neurons and Show Long-Term Survival in Adult Rodent Hippocampus
- 2017
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Ingår i: Stem Cells International. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2017
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Tidskriftsartikel (refereegranskat)abstract
- Direct conversion of human somatic cells to induced neurons (iNs), using lineage-specific transcription factors has opened new opportunities for cell therapy in a number of neurological diseases, including epilepsy. In most severe cases of epilepsy, seizures often originate in the hippocampus, where populations of inhibitory interneurons degenerate. Thus, iNs could be of potential use to replace these lost interneurons. It is not known, however, if iNs survive and maintain functional neuronal properties for prolonged time periods in in vivo. We transplanted human fibroblast-derived iNs into the adult rat hippocampus and observed a progressive morphological differentiation, with more developed dendritic arborisation at six months as compared to one month. This was accompanied by mature electrophysiological properties and fast high amplitude action potentials at six months after transplantation. This proof-of-principle study suggests that human iNs can be developed as a candidate source for cell replacement therapy in temporal lobe epilepsy.
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| 8. |
- Basit, Farhan, et al.
(författare)
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The MYC/Max/MxD network is a target of mutated FLT3 signaling in hematopoietic stem cells in FLT3-ITD-induced myeloproliferative disease
- 2018
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Ingår i: Stem Cells International. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2018
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) has poor prognosis due to various mutations, e.g., in the FLT3 gene. Therefore, it is important to identify pathways regulated by the activated Flt3 receptor for the discovery of new therapeutic targets. The Myc network of oncogenes and tumor suppressor genes is involved in mechanisms regulating proliferation and survival of cells, including that of the hematopoietic system. In this study, we evaluated the expression of the Myc oncogenes and Mxd antagonists in hematopoietic stem cell and myeloid progenitor populations in the Flt3-ITD-knockin myeloproliferative mouse model. Our data shows that the expression of Myc network genes is changed in Flt3-ITD mice compared with the wild type. Mycn is increased in multipotent progenitors and in the pre-GM compartment of myeloid progenitors in the ITD mice while the expression of several genes in the tumor suppressor Mxd family, including Mxd1, Mxd2, and Mxd4, is concomitantly downregulated, as well as the expression of the Mxd-related gene Mnt and the transcriptional activator Miz-1. LSKCD150 + CD48 − hematopoietic long-term stem cells are decreased in the Flt3-ITD cells while multipotent progenitors are increased. Of note, PKC412-mediated inhibition of Flt3-ITD signaling results in downregulation of cMyc and upregulation of the Myc antagonists Mxd1, Mxd2, and Mxd4. Our data provides new mechanistic insights into downstream alterations upon aberrant Flt3 signaling and rationale for combination therapies for tyrosine kinase inhibitors with Myc antagonists in treating AML.
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| 9. |
- Berglund, Sofia, et al.
(författare)
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Expansion of Gammadelta T Cells from Cord Blood : A Therapeutical Possibility
- 2018
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Ingår i: STEM CELLS INTERNATIONAL. - : HINDAWI LTD. - 1687-966X .- 1687-9678.
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Tidskriftsartikel (refereegranskat)abstract
- Gammadelta (gamma delta) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of gamma delta T cells in umbilical cord blood (UCB) is low, and the majority express delta 1, in contrast to blood, whereas the main subset is delta 2 gamma 9 T cells. UCB gamma delta T cells are functionally immature, which together with their scarcity complicates the development of UCB gamma delta T cell therapies. We aimed to develop an effective expansion protocol for UCB gamma delta T cells based on zoledronate and IL-2. We found that culture with 5 mu M zoledronate and 200 IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were gamma 9 delta 2 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal gamma delta T cell repertoire and the main memory subset was central memory (CD45RO(+) CD27(+)). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of in vitro expanded UCB gamma delta T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.
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| 10. |
- Bergström, Tomas F.
(författare)
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Assessment of Hereditary Retinal Degeneration in the English Springer Spaniel Dog and Disease Relationship to an RPGRIP1 Mutation
- 2012
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Ingår i: Stem Cells International. - : Hindawi Limited. - 1687-966X .- 1687-9678.
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Tidskriftsartikel (refereegranskat)abstract
- Intensive breeding and selection on desired traits have produced high rates of inherited diseases in dogs. Hereditary retinal degeneration, often called progressive retinal atrophy (PRA), is prevalent in dogs with disease entities comparable to human retinitis pigmentosa (RP) and Leber's congenital amaurosis (LCA). Recent molecular studies in the English Springer Spaniel (ESS) dog have shown that PRA cases are often homozygous for a mutation in the RPGRIP1 gene, the defect also causing human RP, LCA, and cone rod dystrophies. The present study characterizes the disease in a group of affected ESS in USA, using clinical, functional, and morphological studies. An objective evaluation of retinal function using electroretinography (ERG) is further performed in a masked fashion in a group of American ESS dogs, with the examiner masked to the genetic status of the dogs. Only 4 of 6 homozygous animals showed clinical signs of disease, emphasizing the need and importance for more precise studies on the clinical expression of molecular defects before utilizing animal models for translational research, such as when using stem cells for therapeutic intervention.
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