Abstract:
:Currently, different techniques to expand human hepatocytes in vitro are being investigated to generate enough cells for liver-directed cell therapies. However, based on observations in fibroblasts and other cell types, telomere attrition limits the proliferative capacity of normal somatic cells. Therefore, we explored whether telomere-dependent replicative aging restricts the in vitro proliferation of human hepatocytes. Subpopulations of cells isolated from a neonatal liver and characterized as hepatocyte derived by RT-PCR and flow cytometry started to proliferate 5-7 days after plating and were termed proliferating human hepatocytes (PHH). Following retroviral-mediated transduction of the catalytic telomerase subunit, telomerase reverse transcriptase (hTERT), telomerase activity increased from almost undetectable levels to levels as high as in HepG2 and other telomerase-positive cell lines. As expected, untransduced PHH progressively lost telomeric repeats and arrested after 30-35 cell divisions with telomeres of less than 5 kilo bases. In comparison, telomerase-reconstituted PHH maintained elongated telomeres and continued to proliferate as shown by colorimetric assays and cell counts. In this study, telomere stabilization extended the proliferative capacity of in vitro proliferating human neonatal hepatocytes. Therefore, telomere attrition needs to be addressed when developing techniques to expand human hepatocytes.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Wege H,Chui MS,Le HT,Strom SC,Zern MAdoi
10.3727/000000003771000138subject
Has Abstractpub_date
2003-01-01 00:00:00pages
897-906issue
8eissn
0963-6897issn
1555-3892journal_volume
12pub_type
杂志文章abstract::Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients w...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689718823206
更新日期:2019-06-01 00:00:00
abstract::Development of a tissue-engineered neo-kidney augment (NKA) requires evaluation of defined, therapeutically relevant cell and cell/biomaterial composites (NKA constructs) for regenerative potential in mammalian kidney. Previous work identified primary renal cell populations that extended survival and improved renal f...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368911X566172
更新日期:2011-01-01 00:00:00
abstract::The transplantation of porcine islets of Langerhans to treat type 1 diabetes may provide a solution to the demand for insulin-producing cells. Porcine islets encapsulated in agarose-agarose macrobeads have been shown to function in nonimmunosuppressed xenogeneic models of both streptozotocin-induced and autoimmune typ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368913X667033
更新日期:2014-01-01 00:00:00
abstract::Stem cell-based therapy shows great potential in stroke patients. Intra-artery infusion exhibits greater biological distribution compared to intravenous delivery. In addition, umbilical cord mesenchymal stem cells (UCMSCs) have several advantages compared with other types of stem cells. The aim of this study was to ev...
journal_title:Cell transplantation
pub_type: 临床试验,杂志文章
doi:10.3727/096368912X658818
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Extracellular vesicles (EVs) released from mesenchymal stem/stromal cells (MSCs) mediate their paracrine effect, but their efficacy to protect the microcirculation of the kidney is unknown. Using a novel swine model of unilateral renovascular disease (RVD) complicated by metabolic syndrome (MetS), we tested ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689718780942
更新日期:2018-07-01 00:00:00
abstract::The recent advent of endoscopy has enabled the endoscopic submucosal dissection (ESD) of superficial nonampullary duodenal epithelial tumors. However, the substantially thin wall and presence of bile and pancreatic juice make it technically difficult to perform duodenal ESD without perforation, which leads to lethal c...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689720963882
更新日期:2020-01-01 00:00:00
abstract::Electrostimulation represents a well-known trophic factor for different tissues. In vitro electrostimulation of non-stem and stem cells induces myogenic predifferentiation and may be a powerful tool to generate cells with the capacity to respond to local areas of injury. We evaluated the effects of in vivo electrostim...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368912X652977
更新日期:2013-01-01 00:00:00
abstract::Isolation of islets from market-sized pigs is costly, with considerable islet losses from fragmentation occurring during isolation and tissue culture. Fetal and neonatal pigs yield insulin unresponsive islet-like cell clusters that become glucose-responsive after extended periods of time. Both issues impact clinical a...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368912X662372
更新日期:2014-03-01 00:00:00
abstract::The third-generation NOD/LtSz-scid/IL2Rγ(null) (NOD/SCID IL2Rγ(null)) mouse represents a significantly improved xenograft model allowing high levels of human leukocyte engraftment over extended follow up. One remaining limitation of this mouse model, however, is the low level of circulating human erythrocytes. We esta...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368910X314161
更新日期:2010-01-01 00:00:00
abstract::There are conflicting reports on the survival and immune reaction to allografts and xenografts of cultured skin substitutes (CSS). In this study, we investigated the allogeneic and xenogeneic responses to CSS of human keratinocytes and genetically engineered CSS expressing keratinocyte growth factor (KGF) that forms a...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000004783983594
更新日期:2004-01-01 00:00:00
abstract::The use of regenerative medicine to treat nervous system disorders like ataxia has been proposed to either replace or support degenerating neurons. In this study, we assessed the ability of human neural progenitor cells (hNPCs) to repair and restore the function of dying neurons within the spastic Han-Wistar rat (sHW)...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689717723637
更新日期:2017-11-01 00:00:00
abstract::The integrity of the blood-brain barrier (BBB) plays a vital role in affecting the prognosis of subarachnoid hemorrhage (SAH). This study aimed to investigate activation of the Tropomyosin-related kinase receptor B (TrkB) and its downstream signaling pathway on preserving BBB breakdown after experimental SAH. An endov...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689719857649
更新日期:2019-08-01 00:00:00
abstract::Cell-based therapy for the bladder has its beginnings in the 1990s with the successful isolation and culture of bladder smooth muscle cells. Since then, several attempts have been made to artificially implant native cell types and stem cell-derived cells into damaged bladders in the form of single-cell injectables or ...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.3727/096368914X685050
更新日期:2015-01-01 00:00:00
abstract::It is difficult to normalize plasma glucose for a prolonged period of time by s.c. injection in experimental animals. The goal of this study was to determine the feasibility and the dosage of insulin needed to maintain 24-h normoglycemia in streptozotocin-diabetic Syrian hamsters with a s.c.-implanted osmotic minipump...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368979900800511
更新日期:1999-09-01 00:00:00
abstract::Huntington's disease (HD) is a devastating neurodegenerative disorder that occurs in patients with a mutation in the huntingtin or IT15 gene. Patients are plagued by early cognitive signs, motor deficits, and psychiatric disturbances. Symptoms are attributed to cell death in the striatum and disruption of cortical-str...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.3727/000000007783464687
更新日期:2007-01-01 00:00:00
abstract::Rare cells are present in human umbilical cord blood that do not express the hematopoietic marker CD45 and in culture do not produce cells of hematopoietic lineage. These umbilical cord multipotent stem cells (UC-MC) behave as multilineage progenitor cells (stem cells) and can be expanded in tissue culture. Exposure t...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096020197390022
更新日期:2002-04-01 00:00:00
abstract::Efficient maintenance of the undifferentiated status of embryonic stem cells (ESCs) may be important for preparation of high-quality cell sources that can be successfully used for stem cell research and therapy. Here we tried to identify a compound that can enhance the quality of pluripotent stem cells. Treatment of E...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368914X683511
更新日期:2015-01-01 00:00:00
abstract::Recently, animal studies have demonstrated the efficacy of endothelial progenitor cell (EPC) therapy for diabetic wound healing. Based on these preclinical studies, we performed a prospective clinical trial phase I/IIa study of autologous G-CSF-mobilized peripheral blood (PB) CD34(+) cell transplantation for nonhealin...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368912X658007
更新日期:2014-02-01 00:00:00
abstract::Previously, we found that hepatocyte growth factor receptor (c-Met)-and alpha-fetoprotein (AFP)-expressing cells were present in adult rat bone marrow, and that these cells also expressed hematopoietic stem cell markers, such as CD34, Thy-1, and c-Kit. When bone marrow cells were cultured in a hepatocyte growth medium...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000004783983800
更新日期:2004-01-01 00:00:00
abstract::Several previous studies, suggesting the potential use of embryonic xenografts in the treatment of neurological disorders, indicate that neural growth and axonal guidance factors may function across species. In this light, blocks of fetal porcine neocortex were grafted into small cortical lesion cavities made in newbo...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000003108747343
更新日期:2003-01-01 00:00:00
abstract::Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689720978219
更新日期:2021-01-01 00:00:00
abstract::The revascularization of islets of Langerhans transplanted in heterotopic sites like the liver by portal vein embolization or the renal subcapsular space is a major process necessary for the viability of grafted cells. This process has been extensively studied by different techniques and the results have shown that is...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1016/s0963-6897(97)00099-7
更新日期:1997-11-01 00:00:00
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journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368915X686995
更新日期:2015-01-01 00:00:00
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::Hematopoietic stem and progenitor cells reside within the bone marrow (BM) microenvironment. By a well-balanced interplay between self-renewal and differentiation, they ensure a lifelong supply of mature blood cells. Physiologically, multiple different cell types contribute to the regulation of stem and progenitor cel...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.1177/0963689717745890
更新日期:2018-05-01 00:00:00
abstract::Testis-derived Sertoli cells have been used to create an immune "privileged" site outside of the testis to facilitate cell transplantation protocols for diabetes and neurodegenerative diseases. In addition to secreting immunoprotective factors, Sertoli cells also secrete growth and trophic factors that appear to enhan...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1016/s0963-6897(97)00022-5
更新日期:1997-03-01 00:00:00
abstract::Insufficient oxygenation can limit the long-term survival of encapsulated islets in subcutaneous tissue. Transplantation of coencapsulated pig islets with adipose or bone marrow mesenchymal stem cells (AMSCs or BM-MSCs, respectively) was investigated with regard to implant vascularization, oxygenation, and diabetes co...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368913X663550
更新日期:2014-01-01 00:00:00
abstract::Grafting autologous cultured satellite cells in irreversibly injured rat extensor digitorum longus EDL muscle leads to myofiber regeneration at the grafting site. In this study, we investigated whether cell grafts induced functional improvement and correlated mechanophysiological findings with histological observation...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368979400300103
更新日期:1994-01-01 00:00:00
abstract::Ex vivo embryonic liver explant culture is a novel and attractive approach to obtain abundant hepatic and hematopoietic stem cells. Gene therapy of autologous hepatic and hematopoietic stem cells represents an alternative therapeutic approach to liver transplantation for genetic and metabolic disorders. In this study ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000001783986945
更新日期:2001-01-01 00:00:00
abstract::Membrane integrity fluorescent staining is used routinely to evaluate islet viability. Results are used as one of the determining factors in islet product release criteria, and are used to assess the efficacy of different culture conditions. Recently, it has been observed that there is variation in the viability stain...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000004783983701
更新日期:2004-01-01 00:00:00