Abstract:
:In a companion article, we describe the engineering and characterization of pituitary GH3 cell clones stably transfected with a furin-cleavable human insulin cDNA (InsGH3 cells). This article describes the performance of InsGH3 (clones 1 and 7) cell grafts into streptozotocin (STZ)-induced diabetic nude mice. Subcutaneous implantation of 2 x 10(6) InsGH3 cells resulted in the progressive reversal of hyperglycemia and diabetic symptoms, even though the progressive growth of the transplanted cells (clone 7) eventually led to glycemic levels below the normal mouse range. Proinsulin transgene expression was maintained in harvested InsGH3 grafts that, conversely, lose the expression of the prolactin (PRL) gene. Elevated concentrations of circulating mature human insulin were detected in graft recipients, demonstrating that proinsulin processing by InsGH3 cells did occur in vivo. Histologic analysis showed that transplanted InsGH3 grew in forms of encapsulated tumors composed of cells with small cytoplasms weakly stained for the presence of insulin. Conversely, intense insulin immunoreactivity was detected in graft-draining venules. Compared to pancreatic betaTC3 cells, InsGH3 cells showed in vitro a higher rate of replication, an elevate resistance to apoptosis induced by serum deprivation and proinflammatory cytokines, and significantly higher antiapoptotic Bcl-2 protein levels. Moreover, InsGH3 cells were resistant to the streptozotocin toxicity that, in contrast, reduced betaTC3 cell viability to 50-60% of controls. In conclusion, proinsulin gene expression and mature insulin secretion persisted in transplanted InsGH3 cells that reversed hyperglycemia in vivo. InsGH3 cells might represent a potential beta-cell surrogate because they are more resistant than pancreatic beta cells to different apoptotic insults and might therefore be particularly suitable for encapsulation.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Davalli AM,Galbiati F,Bertuzzi F,Polastri L,Pontiroli AE,Perego L,Freschi M,Pozza G,Folli F,Meoni Cdoi
10.1177/096368970000900610subject
Has Abstractpub_date
2000-11-01 00:00:00pages
841-51issue
6eissn
0963-6897issn
1555-3892journal_volume
9pub_type
杂志文章abstract::Experiments on spinal cord injury (SCI) have largely focused on the transplantation of stem cells into injured spinal cords for motor recovery while neglecting to investigate bladder dysfunction. The present study was performed to investigate the effect of B10 human mesenchymal stem cells (hMSCs) directly transplanted...
journal_title:Cell transplantation
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abstract::Cell therapy has attracted considerable interest as a promising therapeutic alternative for patients with Parkinson's disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited an...
journal_title:Cell transplantation
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abstract::Acute myocardial infarction (AMI) results in ischemic damage and death of cardiomyocytes and loss of vasculature. Stem cell therapy has emerged as a potentially promising strategy for maximizing cardiac function following ischemic injury. Issues of cell source, delivery, and quantification of response have challenged...
journal_title:Cell transplantation
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journal_title:Cell transplantation
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abstract::Pancreas procurement for islet isolation and transplantation is limited by concerns for the detrimental effects of postmortem ischemia. Hypothermic machine perfusion (HMP) preservation technology has had a major impact in circumventing ischemic injury in clinical kidney transplantation and is applied here to the prese...
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abstract::Maintenance of freshly isolated porcine liver cells in vitro is limited for a short period of time. Therefore, establishment of easy handling cell lines is extremely important for in vitro study for liver cells and their possible utilization for cell differentiation and growth of stem cells. Porcine liver cells were t...
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abstract::Osteoarthritis (OA) is degenerative disease, leading to pain and functional disability. It is reported that polydeoxyribonucleotide (PDRN) is a suitable therapy for OA. However, the therapeutic mechanisms of PDRN in OA are not fully understood. To investigate the effect of PDRN in an in vitro model of OA, interleukin ...
journal_title:Cell transplantation
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abstract::Near infrared fluorescence (NIRF) optical imaging is a technique particularly powerful when studying in vivo processes at the molecular level in preclinical animal models. We recently demonstrated liver irradiation under the additional stimulus of partial hepatectomy as being an effective primer in the rat liver repop...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
abstract::Cardiac cell therapy with mesenchymal stem cells (MSCs) represents a promising treatment approach for end-stage heart failure. However, little is known about the underlying mechanisms and the fate of the transplanted cells. The objective of the presented work is to determine the feasibility of magnetic resonance imagi...
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abstract::Hypoxia is an adverse condition that can jeopardize the function of a bioartificial pancreatic construct. In this study we have investigated the effects of short-term hypoxic exposure (up to 24 h) on the bioenergetic status, metabolism, and insulin secretion of perfused pancreatic constructs composed of alginate/poly-...
journal_title:Cell transplantation
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doi:10.1177/096368970000900312
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abstract::Human islets are subjected to a number of stresses before and during their isolation that may influence their survival and engraftment after transplantation. Apoptosis is likely to be activated in response to these stresses. Apoptosis due to intrinsic stresses is regulated by pro- and antiapoptotic members of the Bcl...
journal_title:Cell transplantation
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abstract::The therapeutic use of stem cells to treat diseases and injuries is a promising tool in regenerative medicine. The umbilical cord provides a rich source of stem cells; we have previously reported a population of stem cells isolated from Wharton's jelly. In this report, we aimed to isolate a novel cell population that ...
journal_title:Cell transplantation
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doi:10.3727/096368912X655064
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abstract::Fetal rat kidney cells produce high levels of glial-derived neurotrophic factor (GDNF) and exert neuroprotective effects when transplanted into the brain in animal models of Parkinson's disease and stroke. The purpose of the present experiment was to produce kidney cell lines that secrete GDNF. Genes encoding two trun...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::The effect of tensile stress on the orientation and phenotype of arterial smooth muscle cells (SMCs) cultured in three-dimensional (3D) type I collagen gels was morphologically investigated. Ring-shaped hybrid tissues were prepared by thermal gelation of a cold mixed solution of type I collagen and SMCs derived from b...
journal_title:Cell transplantation
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abstract::Testicular germ cell tumors (TGCTs) are highly prevalent in young men aged 20-40 years and are one of the most common lethal solid tumors in men of this age. Due to the current unclear mechanism of tumor development, there is a lack of effective treatment, and therefore in-depth research of the molecular mechanism of ...
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journal_title:Cell transplantation
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journal_title:Cell transplantation
pub_type: 杂志文章,评审
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abstract::Expression of a fluorescent reporter gene has been studied using two alternate promoters to transcribe the green fluorescent protein (gfp) from Aequorea victoria. The human cytomegalovirus (CMV) enhancer/ promoter or the human muscle-specific creatine kinase promoter (CKM) were inserted along with the gfp cDNA into a ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1016/0963-6897(95)02026-8
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abstract::In this study, we assessed the ability of miR-26b-5p to regulate T cell factor 4 (TCF-4) expression and thereby control human adipose-derived mesenchymal stem cell (hADMSC) adipogenic differentiation. Adipogenic medium was used to induce hADMSC differentiation over a 6-d period. The ability of miR-26b-5p to interact w...
journal_title:Cell transplantation
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abstract::Current good manufacturing practice (cGMP) islet processing facilities provide an ultraclean environment for the safe production of clinical grade islets for transplantation into immunosuppressed diabetic recipients. The objective of this study was to monitor the rate of microbial contamination in islet products after...
journal_title:Cell transplantation
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abstract::Despite recent advances and promising results in children, liver cell transplantation (LCT) should still be regarded as an experimental therapy. Several substantial complications are known from animal studies and individual patients. However, safety data on liver cell infusion in children are scarce. We used LCT in fo...
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pub_type: 临床试验,杂志文章
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abstract::Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited myopathy. We previously demonstrated that mesoangioblasts can be efficiently isolated from FSHD muscles, although their differentiation ability into skeletal muscle was variably impaired. This correlates with overall disease severity a...
journal_title:Cell transplantation
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journal_title:Cell transplantation
pub_type: 杂志文章,评审
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更新日期:1998-11-01 00:00:00
abstract::Ten mongrel dogs were used in this study. Diabetes was chemically induced in 7 dogs, and 3 dogs served as normal controls. For each diabetic dog, 5 million human bone marrow-derived mesenchymal stem cells/kg were differentiated to form insulin-producing cells using a trichostatin-based protocol. Cells were then loaded...
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