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  • SAGE Publications  (11)
  • English  (11)
  • 2010-2014  (11)
  • 1
    In: Journal of Child Neurology, SAGE Publications, Vol. 26, No. 8 ( 2011-08), p. 1015-1020
    Abstract: Intracranial arteriovenous fistulas are vascular malformations in which clinical suspicion and prompt diagnosis, with a subsequent appropriate therapeutic approach, are crucial to avoid the development of irreversible neurological damage or even patient death because these lesions can be associated with heavy bleeding and high mortality rates. The authors present the case of a direct pial arteriovenous fistula in an infant and its unusual presentation as a large occipital protuberance with hard consistency and an audible murmur that produced bone remodeling. The patient was successfully treated by endovascular therapy, with complete regression of the occipital protuberance during follow-up.
    Type of Medium: Online Resource
    ISSN: 0883-0738 , 1708-8283
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 2068710-2
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  • 2
    In: Cell Transplantation, SAGE Publications, Vol. 19, No. 6-7 ( 2010-06), p. 655-665
    Abstract: Cell populations derived from adult tissue and stem cells possess a great expectation for the treatment of several diseases. Great efforts have been made to generate cells with therapeutic impact from stem cells. However, it is clear that the development of systems to deliver such cells to induce efficient engraftment, growth, and function is a real necessity. Biologic and artificial scaffolds have received significant attention for their potential therapeutic application when use to form tissues in vitro and facilitate engraftment in vivo. Ultimately more sophisticated methods for decellularization of organs have been successfully used in tissue engineering and regenerative medicine applications. These decellularized tissues and organs appear to provide bioactive molecules and bioinductive properties to induce homing, differentiation, and proliferation of cells. The combination of decellularized organs and stem cells may dramatically improve the survival, engraftment, and fate control of transplanted stem cells and their ultimate clinical utility, opening the doors to a new era of organ engineering.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2020466-8
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  • 3
    In: European Journal of Ophthalmology, SAGE Publications, Vol. 21, No. 4 ( 2011-07), p. 498-502
    Abstract: TO report clinical and confocal microscopy features of late-onset Candida albicans keratitis after Descemet stripping automated keratoplasty (DSAEK). Methods We performed clinical and confocal scan on a patient who underwent DSAEK and phacoemulsification for Fuchs endothelial dystrophy and cataract. Results A 76-year-old woman who underwent uneventful DSAEK and phacoemulsification presented with white to cream deposits 3 months after DSAEK. Confocal microscopy showed a hyperintense deposit at the lenticule and interface. Confocal scan also disclosed intense haze and inflammation at the interface and clusters of hyperreflective round structures resembling epithelial cells within the interface area. No signs of hyphae-like structures were seen. Late-onset symptoms misled us into a bacterial chronic endophthalmitis diagnosis, and the patient was started on topical and systemic antibiotics. Despite intense antibiotic therapy, the patient developed severe endophthalmitis, so we performed anterior vitrectomy and the donor lenticule was removed. Microbiology results from the removed lenticule showed infection by C albicans. Antifungal therapy with systemic and topical voriconazole controlled the infection. Conclusions Candida interface keratitis is possible after DSAEK. The posterior location of infected tissue poses diagnostic and therapeutic challenges. In our case, the late onset of the symptoms and not performing corneoscleral rim cultures delayed correct diagnosis. This is the first reported case of post-DSAEK Candida keratitis with confocal microscopy images. A hyperintense granular deposit was seen at the lenticule and interface with confocal microscopy. We also observed intense haze, granular round structures resembling epithelial cells, and hyperreflective needle-shaped material at the interface. No hyphae-like structures were seen with confocal imaging.
    Type of Medium: Online Resource
    ISSN: 1120-6721 , 1724-6016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 1475018-1
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  • 4
    In: Cell Transplantation, SAGE Publications, Vol. 22, No. 2 ( 2013-02), p. 231-242
    Abstract: At this time, the only definitive treatment of hepatic failure is liver transplantation. However, transplantation has been limited by the severely limited supply of human donor livers. Alternatively, a regenerative medicine approach has been recently proposed in rodents that describe the production of three-dimensional whole-organ scaffolds for assembly of engineered complete organs. In the present study, we describe the decellularization of porcine livers to generate liver constructs at a scale that can be clinically relevant. Adult ischemic porcine livers were successfully decellularized using a customized perfusion protocol, the decellularization process preserved the ultrastructural extracellular matrix components, functional characteristics of the native microvascular and the bile drainage network of the liver, and growth factors necessary for angiogenesis and liver regeneration. Furthermore, isolated hepatocytes engrafted and reorganized in the porcine decellularized livers using a human-sized organ culture system. These results provide proof-of-principle for the generation of a human-sized, three-dimensional organ scaffold as a potential structure for human liver grafts reconstruction for transplantation to treat liver disease.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
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  • 5
    In: Cell Transplantation, SAGE Publications, Vol. 19, No. 6-7 ( 2010-06), p. 783-789
    Abstract: Elimination of galactose-α( 1 , 3 )galactose (Gal) expression in pig organs has been previously shown to prevent hyperacute xenograft rejection. However, naturally present antibodies to non-Gal epitopes activate endothelial cells, leading to acute humoral xenograft rejection. Still, it is unknown whether xenogeneic pig liver sinusoidal endothelial cells (LSECs) from α( 1 , 3 )galactosyltransferase (GalT)-deficient pigs are damaged by antibody and complement-mediated mechanisms. The present study examined the xeno-antibody response of LSECs from GalT-deficient and wild pigs. Isolated LSEC from wild-type and GalT pigs were expose to human and baboon sera; IgM and IgG binding was analyzed by flow cytometry. Complement activation (C3a and CH50) was quantified in vitro from serum-exposed LSEC cultures using Enzyme-Linked ImmunoSorbent assay (ELISA). Levels of complement-activated cytotoxicity (CAC) were also determined by a fluorescent Live-Dead Assay and by the quantification of LDH release. IgM binding to GalT knockout (KO) LSECs was significantly lower (80% human and 87% baboon) compare to wild-type pig LSEC. IgG binding was low in all groups. Moreover, complement activation (C3a and CH50) levels released following exposure to human or baboon sera were importantly reduced (42% human and 52% baboon), CAC in GalT KO LSECs was reduced by 60% in human serum and by 72% in baboon serum when compared to wild-type LSECs, and LDH release levels were reduced by 37% and 57%, respectively. LSECs from GalT KO pigs exhibit a significant protection to humoral-induced cell damage compared to LSECs from wild pigs when exposed to human serum. Although insufficient to inhibit xenogeneic reactivity completely, transgenic GalT KO expression on pig livers might contribute to a successful application of clinical xenotransplantation in combination with other protective strategies.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 6
    Online Resource
    Online Resource
    SAGE Publications ; 2010
    In:  Cell Transplantation Vol. 19, No. 6-7 ( 2010-06), p. 667-679
    In: Cell Transplantation, SAGE Publications, Vol. 19, No. 6-7 ( 2010-06), p. 667-679
    Abstract: Mesenchymal stem cell (MSC) transplantation has been explored as a new clinical approach to repair injured tissue. A growing corpus of studies have highlighted two important aspects of MSC therapy: 1) MSCs can modulate T-cell-mediated immunological responses, and ( 2 ) systemically administered MSCs home to sites of ischemia or injury. In this review, we describe the known mechanisms of immunomodulation and homing of MSCs. First, we examine the low immunogenicity of MSCs and their antigen presentation capabilities. Next, we discuss the paracrine interactions between MSCs and innate [dendritic cells (DC)] and adaptive immune cells (T lymphocytes) with a focus on prostaglandin E 2 (PGE 2 ), indoleamine 2,3-dioxygenase (IDO), and toll-like receptor (TLR) signaling pathways. We transition to outline the steps of activation, rolling/adhesion, and transmigration of MSCs into target tissues during inflammatory or ischemic conditions. These aspects of MSC grafts—immunomodulation and homing—are contextualized to understand a reported side effect of MSC therapy, cancer development.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2020466-8
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  • 7
    In: Cell Transplantation, SAGE Publications, Vol. 19, No. 6-7 ( 2010-06), p. 799-806
    Abstract: Liver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited supply, the use of porcine hepatocytes might address this problem. Regardless of the source, once isolated hepatocytes lose specific functionality due to the loss of the natural microenvironment. For this reason, we tested the ability of a self-assembling peptide nanofiber (SAPNF) to provide a provisional three-dimensional (3D) support to interact with cells to control their function in vivo. Isolated porcine hepatocytes were embedded in SAPNF, or collagen type I and transplanted by direct injection into the splenic pulp of SCID mice suffering from acute liver failure (ALF) by 90% hepatectomy. SAPNF porcine hepatocyte transplantation produced engraftment that was far superior to that obtained using collagen and prolonged the survival of mice with ALF, in contrast with controls. An ultrastructural evaluation using transmission electron microscopy indicated extensive cell–cell communication and preservation of hepatocyte architecture. The transplanted SAPNF hepatocytes showed higher expression of albumin and PAS and lower apoptotic events assessed by TUNEL staining. Hepatocytes culture in a truly 3D network allows in vivo maintaining of differentiated functions, and once transplanted between widely divergent species can function to correct acute liver failure in mice and prolong their survival.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 8
    In: Cell Transplantation, SAGE Publications, Vol. 23, No. 1 ( 2014-02), p. 27-38
    Abstract: Hepatocyte transplantation has been used to treat liver disease. The availability of cells for these procedures is quite limited. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) may be a useful source of hepatocytes for basic research and transplantation if efficient and effective differentiation protocols were developed and problems with tumorigenicity could be overcome. Recent evidence suggests that the cell of origin may affect hiPSC differentiation. Thus, hiPSCs generated from hepatocytes may differentiate back to hepatocytes more efficiently than hiPSCs from other cell types. We examined the efficiency of reprogramming adult and fetal human hepatocytes. The present studies report the generation of 40 hiPSC lines from primary human hepatocytes under feeder-free conditions. Of these, 37 hiPSC lines were generated from fetal hepatocytes, 2 hiPSC lines from normal hepatocytes, and 1 hiPSC line from hepatocytes of a patient with Crigler–Najjar syndrome, type 1. All lines were confirmed reprogrammed and expressed markers of pluripotency by gene expression, flow cytometry, immunocytochemistry, and teratoma formation. Fetal hepatocytes were reprogrammed at a frequency over 50-fold higher than adult hepatocytes. Adult hepatocytes were only reprogrammed with six factors, while fetal hepatocytes could be reprogrammed with three (OCT4, SOX2, NANOG) or four factors (OCT4, SOX2, NANOG, LIN28 or OCT4, SOX2, KLF4, C-MYC). The increased reprogramming efficiency of fetal cells was not due to increased transduction efficiency or vector toxicity. These studies confirm that hiPSCs can be generated from adult and fetal hepatocytes including those with genetic diseases. Fetal hepatocytes reprogram much more efficiently than adult hepatocytes, although both could serve as useful sources of hiPSC-derived hepatocytes for basic research or transplantation.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
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  • 9
    Online Resource
    Online Resource
    SAGE Publications ; 2010
    In:  Cell Transplantation Vol. 19, No. 6-7 ( 2010-06), p. 815-822
    In: Cell Transplantation, SAGE Publications, Vol. 19, No. 6-7 ( 2010-06), p. 815-822
    Abstract: Cell-based technologies to support/restore liver function represent one of the most promising opportunities in the treatment of acute liver failure. However, the understanding of the constituent cell types that interact to achieve liver-specific structure and function has not been achieved in the development of liver assist devices (LADs). Here we show that hepatocytes migrated toward and adhered and formed sinusoids-like structures in conjunction with liver nonparenchymal cells, and that this liver organoid formed sophisticated tissue after 7 days in an implanted LAD in rodents. Hepatocytes only or in combination with human nonparenchymal liver cell lines (endothelial, cholangiocytes, and stellate cells) were cultured in Matrigel. Ultrastructural analysis showed that the hepatocyte-decorated endothelial vascular structures resemble in vivo sinusoids containing plate-like structures, bile canaliculi, and lumen. The sinusoid-like structures retained albumin secretion and drug metabolism capabilities. In addition, LADs containing cocultures of human liver nonparenchymal cells were transplanted in animals for a week; the liver tissue formed sophisticated structures resembling the liver. These results demonstrate the importance of nonparenchymal cells in the cellular composition of LADs. The novelty of the culture's sinusoid-like organization and function strongly support the integration of liver nonparenchymal units into hepatocyte coculture-based LADs as a potential destination therapy for liver failure.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 10
    In: Cell Transplantation, SAGE Publications, Vol. 19, No. 6-7 ( 2010-06), p. 865-877
    Abstract: It has been proposed in human colorectal cancers (CRC) a minority subset of cancer cells within tumors able to initiate tumor growth, defined as cancer stem cells (CSC). Solid human primary colonic and its ovarian metastatic cancer tissues were collected from fresh surgical samples and subsequent xenografts were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The resulting tumors were disaggregated into single-cell suspensions and a CD133 - cell line (NANK) was newly established and analyzed by flow cytometry. Surface markers of progenitor cells were immunophenotypically analyzed, and expression of stem cell and cancer-related genes was characterized. Secreted angiogenesis-associated molecules were investigated by proteomic array technology. Finally, different numbers of NANK were implanted and their tumor-initiating properties were investigated in NOD/SCID mice. Intraperitoneal injection of NANK in NOD/SCID mice induced tumors with developing progressive peritoneal dissemination and ascites. NANK cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Noticeably, NANK lacked the expression of conventional CSC markers CD133 and CD44, self-renewal genes Oct-4 and Nanog, but showed the expression of an important gastrointestinal development marker CDX-2 and BMI-1 that is essential in regulating the proliferative activity of normal and leukemic stem cells. In addition, NANK secreted high amounts of important angiogeneic cytokines. These results provide a novel and extensive model in human CSC for studying the generation and maintenance of phenotypic heterogeneity in CRC.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2020466-8
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