- Pancreatic function and diabetes
- Virus-based gene therapy research
- Lysosomal Storage Disorders Research
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Trypanosoma species research and implications
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Animal Genetics and Reproduction
- Tissue Engineering and Regenerative Medicine
- Cancer Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Xenotransplantation and immune response
- Calcium signaling and nucleotide metabolism
- Graphene research and applications
- Plasma and Flow Control in Aerodynamics
- Glycosylation and Glycoproteins Research
- Research on Leishmaniasis Studies
- Cellular transport and secretion
- Metabolism and Genetic Disorders
- Erythrocyte Function and Pathophysiology
- Nerve injury and regeneration
- Estrogen and related hormone effects
Intel (United States)
2024
Xi'an Medical University
2016
Rice University
2013-2015
McMaster University Medical Centre
1979-2008
McMaster University
1998-2007
Health Sciences Centre
1998-2006
University of Michigan
2002
GTx (United States)
1997
Jackson Laboratory
1994
National Center for Infectious Diseases
1992
The richly functionalized basal plane bonded to polar organic moieties makes graphene oxide (GO) innately hydrophilic. Here, a methodology synthesize fluorinated by oxidizing the of graphite, allowing for tunable hydrophobicity GO, is reported. Fluorine exists as tertiary alkyl fluorides covalently graphitic carbons, and using magic‐angle spinning (MAS) 13 C NMR primary tool chemical structures two types synthesized oxides (FGOs) with significantly different fluorine contents are proposed....
If established cultured cell lines genetically modified to secrete desired gene products could be implanted in different allogeneic recipients without immune rejection, novel would delivered more cost effectively. We tested this strategy by encapsulating mouse Ltk¯ cells transfected with the human growth hormone (hGH) immunoprotective permselective alginate microcapsules. Allogeneic mice these microcapsules demonstrated hGH their circulation (0.1–1.5 ng/ml serum) within first 2 weeks....
Virulent Treponema pallidum reacts poorly with the specific antibodies present in human and rabbit syphilitic sera, a phenomenon often attributed to an outer coat of host serum proteins. Here we additional evidence that limited antigenicity virulent organisms actually is due paucity proteins membrane. Initially, used electron microscopy demonstrate membrane highly susceptible damage from physical manipulation (i.e., centrifugation resuspension) nonionic detergents. Organisms disrupted...
Deficiency of clotting factor IX (FIX) causes hemophilia B in humans. We propose a novel approach to its treatment by engineering FIX-secreting cell lines suitable for implantation different allogeneic hosts. To prevent graft rejection following implantation, the recombinant cells can be protected with biocompatible membranes that permit exit FIX but not entry cellular immune mediators. explore feasibility this approach, we now report on creation mouse Ltk¯ fibroblast deliver through such...
Most of the currently approved human gene therapy protocols depend on genetic modification autologous cells. We propose an alternate and potentially more cost-effective approach by implanting genetically modified "universal" cell lines to deliver desired products nonautologous recipients. The recombinant allogeneic cells are protected from rejection after implantation enclosure within immuno-protective alginate-poly-l-lysine-alginate microcapsules. clinical efficacy this strategy is now...
Microencapsulation of recombinant “universal” cells with immunoprotective membranes is an alternate approach to somatic gene therapy. Therapeutic products secreted by these can be delivered different patients without immunosuppression or genetic modification the host's cells. The encapsulation mammalian cell types (epithelial cells, fibroblasts, and myoblasts) compared among three alginate-based microcapsules: (1) calcium-linked alginate microcapsules a solubilized core...
Most lysosomal enzyme deficiencies are catastrophic illnesses with no generally available treatments. We have used the β-glucuronidase-deficient mouse model of mucopolysaccharidosis type VII (MPS VII) to develop an alternative approach therapy. A "universal" cell line engineered secrete missing is implanted in all recipients requiring same replacement. The cells, although nonautologous, rendered immunologically tolerant by encapsulation microcapsules that provide protection from immune...
Implantation of microencapsulated, nonautologous cells and tissues is an effective method to deliver therapeutic proteins in vivo. Its success depends on the maintenance immunoisolating barrier provided by microcapsule. Thus, one goal development this technology create mechanically stable microcapsules. We have developed osmotic pressure test quantify strength microcapsules exposing alginate a graded series hypotonic solutions quantifying percentage broken The was validated confirming...
A novel approach to cancer gene therapy is implant microcapsules containing nonautologous cells engineered secrete molecules with antineoplastic properties. The efficacy of this treatment now tested in a mouse model bearing HER-2/neu-positive tumors. Nonautologous myoblasts (C2C12) were genetically modified interleukin-2 linked the Fv region humanized antibody affinity HER-2/neu. resulting fusion protein, sFvIL-2, would encompass immune-stimulatory cytokine activity targeted...
To develop a novel strategy of nonautologous somatic gene therapy, we now demonstrate the feasibility culturing genetically modified fibroblasts within an immunoprotective environment and optimal conditions required for their continued survival in vitro. When mouse Ltk(-) transfected with human growth hormone were enclosed permselective microcapsules fabricated from alginate-polylysine-alginate, they to secrete at same rates as nonencapsulated cells. They also proliferate vitro least 1 month...
SUMMARY: About 25% of the total cellular invertase and trehalase activity were found in a purified Neurospora wall preparation. Attempts made to dissociate these enzymes from walls with chemical reagents hydrolytic enzymes. A detergent (Triton X-100), sulphydryl reducing agent (β-mercaptoethanol), chelating (ethylenediaminetetraacetate), concentrated salt solution (1 m-KCl), buffers ranging pH 3 10 did not release them significantly. Snail-gut juice released more than 90% both...
Inhibition of angiogenesis has led to tumor suppression in several cancer models. Although administering purified recombinant antiangiogenic product is effective, alternative approaches through genetic manipulation may be more cost-effective. We propose implant nonautologous cells secreting angiostatin for systemic delivery treatment. These are protected from graft rejection alginate microcapsules function as "micro-organs" deliver vivo. This approach was tested by implanting encapsulated...
Abstract Implanting recombinant cells encapsulated in alginate microcapsules to secrete therapeutic proteins has been proven clinically effective treating several murine models of human diseases. However, once implanted, these cannot be assessed without invasive surgery. We now report the preparation and characterization a novel ferrofluid render visible with magnetic resonance imaging (MRI). The was prepared as colloidal iron oxide stabilized water by alginate. presence particles verified...
The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII caused by deficient beta-glucuronidase activity. Bone marrow transplantation has been shown to correct some their biochemical and pathological abnormalities but its efficacy in correcting neurological functional deficits unknown. We transplanted neonatal mice normal controls evaluated central nervous system function with two behavioral tests: grooming test, developmentally regulated...
Severe hemophilia B is a life-threatening, life long condition caused by absence of or defective coagulation factor IX. Gene therapy could provide an alternative treatment to repeated injection plasma-derived concentrate recombinant We have previously described the use implantable microcapsules containing myoblasts deliver human IX in mice. This study reports generation improved myoblast-specific expression vectors. Mouse myoblast clones transfected with various vectors secreted vitro, at...
Somatic gene therapy using nonautologous recombinant cells immunologically protected with alginate migenetic crocapsules has been successfully used to treat rodent diseases. We now report the delivery of re- combinant products brain in rodents by implanting microencapsulated for purpose eventually treating neurodegenerative diseases this technology. Alginate-poly-L-lysine-alginate micro- capsules enclosing mouse C2C12 myoblasts expressing marker human growth hormone (hGH) at 95 +/- 20...
An alternative and potentially cost-effective approach to somatic gene therapy is engineer a universal cell line secreting the desired product suitable for implantation into different patients without immune rejection. Encapsulating these cells in immunoprotective alginate microcapsules showed that this was effective treating murine models of human diseases. We now report also delivering recombinant products large animals. Canine MDCK encapsulated were able deliver growth hormone...
Abstract A novel form of gene therapy using encapsulated recombinant cells in alginate microcapsules has proven effective treating several animal models human diseases. For neurological deficits rodents with this technology, the size to be reduced for implantation central nervous system (CNS) bypass blood–brain barrier. This article reports development small suitable into mouse CNS. By varying encapsulation protocol, could ranging diameter from 5 2000 μm. The optimal was determined 100–200...