Abstract:
:Traumatic brain injury (TBI), a major cause of mortality and morbidity, affects 10 million people worldwide, with limited treatment options. We have previously shown that (-)-phenserine (Phen), an acetylcholinesterase inhibitor originally designed and tested in clinical phase III trials for Alzheimer's disease, can reduce neurodegeneration after TBI and reduce cognitive impairments induced by mild TBI. In this study, we used a mouse model of moderate to severe TBI by controlled cortical impact to assess the effects of Phen on post-trauma histochemical and behavioral changes. Animals were treated with Phen (2.5 mg/kg, IP, BID) for 5 days started on the day of injury and the effects were evaluated by behavioral and histological examinations at 1 and 2 weeks after injury. Phen significantly attenuated TBI-induced contusion volume, enlargement of the lateral ventricle, and behavioral impairments in motor asymmetry, sensorimotor functions, motor coordination, and balance functions. The morphology of microglia was shifted to an active from a resting form after TBI, and Phen dramatically reduced the ratio of activated to resting microglia, suggesting that Phen also mitigates neuroinflammation after TBI. While Phen has potent anti-acetylcholinesterase activity, its (+) isomer Posiphen shares many neuroprotective properties but is almost completely devoid of anti-acetylcholinesterase activity. We evaluated Posiphen at a similar dose to Phen and found similar mitigation in lateral ventricular size increase, motor asymmetry, motor coordination, and balance function, suggesting the improvement of these histological and behavioral tests by Phen treatment occur via pathways other than anti-acetylcholinesterase inhibition. However, the reduction of lesion size and improvement of sensorimotor function by Posiphen were much smaller than with equivalent doses of Phen. Taken together, these results show that post-injury treatment with Phen over 5 days significantly ameliorates severity of TBI. These data suggest a potential development of this compound for clinical use in TBI therapy.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Hsueh SC,Lecca D,Greig NH,Wang JY,Selman W,Hoffer BJ,Miller JP,Chiang YHdoi
10.1177/0963689719854693subject
Has Abstractpub_date
2019-09-01 00:00:00pages
1183-1196issue
9-10eissn
0963-6897issn
1555-3892journal_volume
28pub_type
杂志文章abstract::It is widely believed that human embryonic stem (huES) cells may represent a valid alternative to donor pancreata as a source of islets for transplantation. Much is known about the transcription factors whose sequential activation results in the generation of islets during pancreatic development. This knowledge has be...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000006783982359
更新日期:2006-01-01 00:00:00
abstract::Oligodendrocyte (OL) replacement can be a promising strategy for spinal cord injury (SCI) repair. However, the poor posttransplantation survival and inhibitory properties to axonal regeneration are two major challenges that limit their use as donor cells for repair of CNS injuries. Therefore, strategies aimed at enhan...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368912X661373
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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::Sepsis is a life-threatening disease that results in excessive stimulation of the host's immune cells. In the animal study, the purpose was to investigate the roles of fresh frozen plasma (FFP) transfusion in shaping the CD4+ T lymphocytes immune response through modulating the secreted exosome protein Galectin-9 in m...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689720947347
更新日期:2020-01-01 00:00:00
abstract::International standards for stem cell treatment of neurological disorders have not yet been established. In particular, specific quantitative methods have not yet been adopted to assess the effectiveness of stem cell treatment. The aim of this study is to evaluate the functional changes detectable by conventional neu...
journal_title:Cell transplantation
pub_type: 临床试验,杂志文章
doi:10.3727/096368912x633761
更新日期:2012-01-01 00:00:00
abstract::Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells characterized by their self-renewal and differentiation potential. Accumulating clinical and preclinical evidence indicate MSCs are a promising cell source for regenerative medical therapies. However, undesirable immortalization, spontaneous trans...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368909788534906
更新日期:2009-01-01 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::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
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::The use of biomaterials has been demonstrated as a viable strategy to promote cell survival and cardiac repair. However, limitations on combinational cell-biomaterial therapies exist, as cellular behavior is influenced by the microenvironment and physical characteristics of the material. Among the different scaffolds ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368915X689794
更新日期:2016-01-01 00:00:00
abstract::Multiple sclerosis (MS) is a severe debilitating disorder characterized by progressive demyelination and axonal damage of the central nervous system (CNS). Current therapies for MS inhibit the immune response and demonstrate reasonable benefits if applied during the early phase of relapsing–remitting MS (RRMS) while t...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368912X657404
更新日期:2013-01-01 00:00:00
abstract::Hepatocyte transplantation is dependent on the availability of good quality human hepatocytes isolated from donor liver tissue. Hepatocytes obtained from livers rejected for transplantation on the grounds of steatosis are often of low viability and not suitable for clinical use. The aim of this study was to evaluate t...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368910X514620
更新日期:2010-01-01 00:00:00
abstract::The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the primate brain in the ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368970000900519
更新日期:2000-09-01 00:00:00
abstract::Transplanted embryonic stem (ES) cells, following myocardial infarction (MI), contribute to limited cardiac repair and regeneration with improved function. Therefore, novel strategies are still needed to understand the effects of genetically modified transplanted stem cells on cardiac remodeling. The present study ev...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368911X627561
更新日期:2012-01-01 00:00:00
abstract::Cerebral palsy (CP) is a common disability which results in permanent chronic motor disability appearing in early childhood. Recently human umbilical cord blood mesenchymal stem cell (hUCB-MSC) infusion has emerged as a promising therapeutic strategy for CP, and the treatment efficacy remains to be confirmed by clinic...
journal_title:Cell transplantation
pub_type: 杂志文章,随机对照试验
doi:10.1177/0963689717729379
更新日期:2018-02-01 00:00:00
abstract::Pancreatic beta cell lines may offer an abundant source of cells for beta-cell replacement in type I diabetes. Using regulatory elements of the bacterial tetracycline (tet) operon for conditional expression of SV40 T antigen oncoprotein in transgenic mouse beta cells, we have shown that reversible immortalization is a...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Traumatic brain injury (TBI), a major contributor to deaths and permanent disability worldwide, has been recently described as a progressive cell death process rather than an acute event. TBI pathophysiology is complicated and can be distinguished by the initial primary injury and the subsequent secondary injury that ...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.3727/096368915X686913
更新日期:2015-01-01 00:00:00
abstract::Neurodegenerative disorders, chronic diseases that can severely affect the patient's daily life, include amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's diseases. However, these diseases all have the common characteristic that they are due to degenerative irreversibility, and thus no efficien...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
doi:10.3727/096368914X678445
更新日期:2014-01-01 00:00:00
abstract::Liver transplantation is the only existing modality for treating decompensated liver cirrhosis. Several factors, such as nonavailability of donors, combined with operative risks, complications associated with rejection, usage of immunosuppressive agents, and cost intensiveness, make this strategy available to only a f...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368910X498241
更新日期:2010-01-01 00:00:00
abstract::This study aimed to explore the characteristics of TGFBR1-epidermal growth factor receptor (EGFR)-CTNNB1-CDH1 axis in regulating the invasion and migration in lung cancer. Using the small interfering RNA technology, EGFR was silenced in H2170 and H1299 cells. Then, the colony formation, migration, and invasion abiliti...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/0963689720969167
更新日期:2020-01-01 00:00:00
abstract::Prairie voles show strong pair bonding with their mating partners, and they demonstrate parental behavior toward their infants, indicating that the prairie vole is a unique animal model for analysis of molecular mechanisms of social behavior. Until a recent study, the signaling pathway of oxytocin was thought to be cr...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368916X690502
更新日期:2016-01-01 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
abstract::In human neonates, immature GABAergic interneurons are markedly affected by an excitotoxic insult. While in adults the interest of cell transplantation has been demonstrated in several neurological disorders, few data are available regarding the immature brain. The low survival rate constitutes a strong limitation in ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368913X670174
更新日期:2014-01-01 00:00:00
abstract::Large-scale sterile methods for isolating hepatocytes are desirable for the development of bioartificial liver support systems. In this study the traditional centrifuge method was compared with the use of a Baylor Rapid Autologous Transfusion (BRAT) machine for isolating large quantities of porcine hepatocytes. After ...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000005783983007
更新日期:2005-01-01 00:00:00
abstract::Transplantation of human cells after isolation and culture has become an important alternative for treatment of acute or chronic skin wounds. To increase the efficacy and reduce cost for transplantation of skin cells, more efficient and accurate techniques for evaluation of cell proliferation are needed. Hemocytometer...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000006783982115
更新日期:2006-01-01 00:00:00
abstract::Porcine islets show notoriously low insulin secretion levels in response to glucose stimulation. While this is somehow expected in the case of immature islets isolated from fetal and neonatal pigs, disappointingly low secretory responses are frequently reported in studies using in vitro-maturated fetal and neonatal is...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368916X693798
更新日期:2017-05-09 00:00:00
abstract::The choice of enzyme blend is critical for successful islet isolation. Islet yield, viability, integrity, and function are important factors that influence the outcome of islet transplantation. Liberase HI has been used as a standard enzyme for pancreas digestion and has successfully produced islets that reversed dia...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368911X623826
更新日期:2012-01-01 00:00:00
abstract::Several clinical trials of bone marrow cell infusion in patients with liver cirrhosis (LC) have shown clinical improvement, despite conflicting results from animal models. We investigated serial pathological features and the clinical impact after autologous bone marrow infusion (ABMI) in patients with advanced LC. Ten...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368910X506863
更新日期:2010-01-01 00:00:00
abstract::Islet-like cell clusters generated from human fetal pancreases between 18-24 wk gestation were able to grow and mature both morphologically and functionally after transplantation under the kidney capsule of athymic nude mice. Grafted tissue, predominantly ductal in appearance was unresponsive to glucose 2 wk after gra...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368979400300509
更新日期:1994-09-01 00:00:00
abstract::A new extracorporeal bioartificial liver using alginate-entrapped hepatocytes was developed and evaluated for its ability to correct the lack of bilirubin conjugation in the Gunn rat. Hepatocytes were harvested from Sprague-Dawley rats by the two-step collagenase perfusion method and then immobilized in Ca(++)-alginat...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368979300200603
更新日期:1993-11-01 00:00:00
abstract::The estimated frequency of MSCs in BM is about 0.001-0.01% of total nucleated cells. Most commonly, one applied therapeutic cell dose is about 1-5 million MSCs/kg body weight, necessitating a reliable, fast, and safe expansion system. The limited availability of MSCs demands for an extensive ex vivo amplification step...
journal_title:Cell transplantation
pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00