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1

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Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model

Ferrari, Daniela ; Zalfa, Cristina ; Rota Nodari, Laura ; [et al.]

Springer Science and Business Media LLC ; 2012

In: Cellular and Molecular Life Sciences Vol. 69, No. 7 ( 2012-4), p. 1193-1210

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In: Cellular and Molecular Life Sciences, Springer Science and Business Media LLC, Vol. 69, No. 7 ( 2012-4), p. 1193-1210

Type of Medium: Online Resource

ISSN: 1420-682X , 1420-9071

URL: Article

DOI: 10.1007/s00018-011-0873-5

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2012

detail.hit.zdb_id: 1458497-9

SSG: 12

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2

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Modulation of Experimental Allergic Encephalomyelitis in Lewis Rats by Administration of a Peptide of Fas Ligand

Ciusani, Emilio ; Gelati, Maurizio ; Frigerio, Simona ; [et al.]

Elsevier BV ; 2001

In: Journal of Autoimmunity Vol. 17, No. 4 ( 2001-12), p. 273-280

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In: Journal of Autoimmunity, Elsevier BV, Vol. 17, No. 4 ( 2001-12), p. 273-280

Type of Medium: Online Resource

ISSN: 0896-8411

URL: Article

DOI: 10.1006/jaut.2001.0554

RVK:

XA 52099

Language: English

Publisher: Elsevier BV

Publication Date: 2001

detail.hit.zdb_id: 1468989-3

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3

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Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats

Zalfa, Cristina ; Rota Nodari, Laura ; Vacchi, Elena ; [et al.]

Springer Science and Business Media LLC ; 2019

In: Cell Death & Disease Vol. 10, No. 5 ( 2019-04-25)

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In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 10, No. 5 ( 2019-04-25)

Abstract: Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS.

Type of Medium: Online Resource

ISSN: 2041-4889

URL: Article

DOI: 10.1038/s41419-019-1582-5

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2541626-1

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4

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Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Perciballi, Elisa ; Bovio, Federica ; Rosati, Jessica ; [et al.]

MDPI AG ; 2022

In: Antioxidants Vol. 11, No. 5 ( 2022-04-22), p. 815-

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In: Antioxidants, MDPI AG, Vol. 11, No. 5 ( 2022-04-22), p. 815-

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism.

Type of Medium: Online Resource

ISSN: 2076-3921

URL: Article

DOI: 10.3390/antiox11050815

Language: English

Publisher: MDPI AG

Publication Date: 2022

detail.hit.zdb_id: 2704216-9

SSG: 15,3

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Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Mazzini, Letizia ; Gelati, Maurizio ; Profico, Daniela Celeste ; [et al.]

Oxford University Press (OUP) ; 2019

In: Stem Cells Translational Medicine Vol. 8, No. 9 ( 2019-09-01), p. 887-897

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In: Stem Cells Translational Medicine, Oxford University Press (OUP), Vol. 8, No. 9 ( 2019-09-01), p. 887-897

Abstract: The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. Stem Cells Translational Medicine 2019;8:887–897

Type of Medium: Online Resource

ISSN: 2157-6564 , 2157-6580

URL: Article

DOI: 10.1002/sctm.18-0154

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2019

detail.hit.zdb_id: 2642270-0

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6

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Transforming Growth Factor-β1 and CD105 Promote the Migration of Hepatocellular Carcinoma–Derived Endothelium

Benetti, Anna ; Berenzi, Angiola ; Gambarotti, Marco ; [et al.]

American Association for Cancer Research (AACR) ; 2008

In: Cancer Research Vol. 68, No. 20 ( 2008-10-15), p. 8626-8634

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In: Cancer Research, American Association for Cancer Research (AACR), Vol. 68, No. 20 ( 2008-10-15), p. 8626-8634

Abstract: Hepatocellular carcinoma (HCC) is one of most malignant and aggressive human tumors. Transforming growth factor-β1 (TGF-β1) and its coreceptor CD105 have been shown to contribute to HCC malignant progression. TGF-β1 and CD105 have also been implicated in angiogenesis, but their role in the vascularization of HCC has not been investigated. To fill this gap, we studied the effect of TGF-β1 and CD105 on HCC-derived endothelium. By using immunomagnetic beads, we isolated and cultured endothelial cells (ECs) from HCC (HCC-EC) and adjacent nonneoplastic tissue (nNL-ECs) obtained from 24 liver biopsies. HCC and nNL biopsies were also analyzed by immunohistochemistry for the expression of CD105, TGF-β1, Ve-cadherin (Ve-cad), CD44, β-catenin, and E-cadherin. Compared with nNL-ECs, HCC-ECs had higher expression of CD105, enhanced spontaneous motility, and greater capacity to migrate in response to TGF-β1 (5 ng/mL), particularly in the presence of a fibronectin matrix. The chemotactic effect of TGF-β1 was blocked by anti-CD105 antibodies and correlated with the grade of HCC malignancy. Histologic examination of HCC biopsies showed that HCCs with the worse malignant features had the highest expression of TGF-β1, CD105, and angiogenic markers (Ve-cad and CD44). Because CD105 was highly expressed in microvessels at the tumor periphery and TGF-β1 staining was only found in neoplastic hepatocytes, we conclude that HCC-derived TGF-β1 may act as a chemoattractant for CD105-expressing ECs and as a promoter of tumor angiogenesis. Thus, drugs that selectively target the TGF-β1/CD105 axis may interfere with HCC-related angiogenesis and HCC progression. [Cancer Res 2008;68(20):8626–34]

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/0008-5472.CAN-08-1218

RVK:

XA 36000

RVK:

XA 10000

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2008

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

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7

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Regulation of Postangiogenic Neovessel Survival by β〈sub〉1〈/sub〉 and β〈sub〉3 〈/sub〉Integrins in Collagen and Fibrin Matrices

Carnevale, Edvige ; Fogel, Eric ; Aplin, Alfred C. ; [et al.]

S. Karger AG ; 2007

In: Journal of Vascular Research Vol. 44, No. 1 ( 2007), p. 40-50

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In: Journal of Vascular Research, S. Karger AG, Vol. 44, No. 1 ( 2007), p. 40-50

Abstract: We used the aortic ring model of angiogenesis to investigate the role of β 〈 sub 〉 1 〈 /sub 〉 and β 〈 sub 〉 3 〈 /sub 〉 integrins in postangiogenic vascular survival in collagen and fibrin matrices. Confocal microscopy studies showed that both β 〈 sub 〉 1 〈 /sub 〉 and β 〈 sub 〉 3 〈 /sub 〉 integrins were expressed in endothelial cells and pericytes of sprouting neovessels. Antibody blocking experiments demonstrated that β 〈 sub 〉 1 〈 /sub 〉 integrins but not β 〈 sub 〉 3 〈 /sub 〉 integrins were required for angiogenic sprouting in collagen. Conversely, in fibrin, blockade of both integrins was needed to inhibit angiogenesis whereas treatment with either antibody alone was ineffective. Antibody-mediated blockade of β 〈 sub 〉 1 〈 /sub 〉 but not β 〈 sub 〉 3 〈 /sub 〉 integrins accelerated vascular regression in collagen. In contrast, both anti-β 〈 sub 〉 1 〈 /sub 〉 and -β 〈 sub 〉 3 〈 /sub 〉 integrin antibodies were required to promote neovessel breakdown in fibrin. These results demonstrate that angiogenic sprouting and postangiogenic neovessel survival in collagen are critically dependent on β 〈 sub 〉 1 〈 /sub 〉 integrins. They also indicate that these processes involve a redundant repertoire of β 〈 sub 〉 1 〈 /sub 〉 and β 〈 sub 〉 3 〈 /sub 〉 integrins when angiogenesis occurs in fibrin. Thus, pharmacologic targeting of integrin receptors aimed at blocking neovessel formation and survival must be tailored to the specific extracellular matrix environment in which angiogenesis takes place.

Type of Medium: Online Resource

ISSN: 1018-1172 , 1423-0135

URL: Article

DOI: 10.1159/000097976

Language: English

Publisher: S. Karger AG

Publication Date: 2007

detail.hit.zdb_id: 1482726-8

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8

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Angiopoietin-1 and vascular endothelial growth factor induce expression of inflammatory cytokines before angiogenesis

Aplin, Alfred C. ; Gelati, Maurizio ; Fogel, Eric ; [et al.]

American Physiological Society ; 2006

In: Physiological Genomics Vol. 27, No. 1 ( 2006-09), p. 20-28

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In: Physiological Genomics, American Physiological Society, Vol. 27, No. 1 ( 2006-09), p. 20-28

Abstract: The purpose of this study was to identify novel transcriptional events occurring in the aortic wall before angiogenesis. We used a defined tissue culture system that takes advantage of the capacity of rat aortic rings to generate neovessels ex vivo in response to angiogenic factor stimulation. Total RNA isolated from aortic rings 18 h posttreatment with angiopoietin (Ang)-1 or vascular endothelial growth factor (VEGF) was used to probe oligonucleotide microarrays. Many genes were up- or downregulated by either Ang-1 or VEGF, with a subset being affected by treatment with both growth factors. Grouping of genes by biological function revealed that Ang-1 and VEGF both upregulated a host of immune-related genes including many inflammatory cytokines. A mixture of the Ang-1- and VEGF-induced cytokines stimulated the spontaneous angiogenic response of aortic rings and was synergistic with a low dose of recombinant VEGF. This effect was associated with enhanced recruitment of adventitial macrophages and dendritic cells in the angiogenic outgrowths. Thus Ang-1 and VEGF activate the innate immune system of the vessel wall, stimulating the production of proangiogenic inflammatory cytokines before the emergence of neovessels. This hitherto unreported feature of the angiogenic response might represent an important early component of the cellular and molecular cascade responsible for the angiogenic response of the aortic wall.

Type of Medium: Online Resource

ISSN: 1094-8341 , 1531-2267

URL: Article

DOI: 10.1152/physiolgenomics.00048.2006

Language: English

Publisher: American Physiological Society

Publication Date: 2006

detail.hit.zdb_id: 2031330-5

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9

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Novel Prion Protein Conformation and Glycotype in Creutzfeldt-Jakob Disease

Zanusso, Gianluigi ; Polo, Alberto ; Farinazzo, Alessia ; [et al.]

American Medical Association (AMA) ; 2007

In: Archives of Neurology Vol. 64, No. 4 ( 2007-04-01), p. 595-

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In: Archives of Neurology, American Medical Association (AMA), Vol. 64, No. 4 ( 2007-04-01), p. 595-

Type of Medium: Online Resource

ISSN: 0003-9942

URL: Article

DOI: 10.1001/archneur.64.4.595

RVK:

XA 10000

Language: English

Publisher: American Medical Association (AMA)

Publication Date: 2007

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Differential effects on angiogenesis of two antimalarial compounds, dihydroartemisinin and artemisone: Implications for embryotoxicity

D’Alessandro, Sarah ; Gelati, Maurizio ; Basilico, Nicoletta ; [et al.]

Elsevier BV ; 2007

In: Toxicology Vol. 241, No. 1-2 ( 2007-11), p. 66-74

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In: Toxicology, Elsevier BV, Vol. 241, No. 1-2 ( 2007-11), p. 66-74

Type of Medium: Online Resource

ISSN: 0300-483X

URL: Article

DOI: 10.1016/j.tox.2007.08.084

Language: English

Publisher: Elsevier BV

Publication Date: 2007

detail.hit.zdb_id: 1500781-9

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Kooperativer Bibliotheksverbund

Berlin Brandenburg