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At least 379 records · Page 21Linked to original sources
PubMed2003

[Encapsulated ANP cDNA transfection cells attenuate hypertension in hypertensive rats].

OBJECTIVE: We Investigated a gene therapy delivery system based on microcapsules enclosing recombinant Chinese hamster ovary (CHO) cells engineered to secrete a therapeutic peptide-atrial natriuretic peptide (ANP). METHOD: Human atrial natriuretic peptide gene transfecting Chinese hamster ovary (CHO) cells were encapsulated in non-antigenic biocompatible polycaprolactone (PCL) capsules prior to their implantation into rats, then, the PCL-tubes were implanted into hypertensive DSS rats intraperitoneally. RESULT: The PCL-tubes 2 d post implantation caused a significant delay of blood pressure increase. The effect lasted for more than 5 months. The PCL-tubes also caused significant increases in renal blood flow, glomerular filtration rate, sodium output, urine excretion. Plasma levels of ANP in rats implanted with the PCL-tubes containing engineering cells is higher than that of the control rats. CONCLUSION: This study demonstrates encapsulated engineering cells have significant potential in treatment of hypertension.

Animals↗
PubMed2001

[Continuously perfused cultivation of genetically-engineered CHO cells producing prothrombin in a modified Super-Spinner].

A Super-Spinner was Modified by mounting a stainless steel filter(pore size 75 microns) to the impeller shaft to retain cells while fresh nutrient is perfused. Using Macroporous microcarrier Cytopore 1, continuously perfused cultivation of a recombinant CHO cell line, CHO2DS producing prothrombin was performed with the perfusion of a protein-free medium DF6S. The cell retention rate was more than 90% during the 24 days continuously perfused cultivation. The viable cell density of CHO2DS and prothrombin concentration reached 4.62 x 10(6)(cells.m/L) and 11.3(mg/L) respectively after 9 days culture.

Animals↗
PubMed2005

Nanostructured designs of biomedical materials: applications of cell sheet engineering to functional regenerative tissues and organs.

Biomaterials surface design is critical for control of cell-materials interactions. Materials surface characteristics important to cell-materials interactions are the following: (a) nonfouling surfaces where cells cannot interact; (b) surfaces that interact with cells but do not alter cell morphology or metabolism (passive adhesion processes); and (c) surfaces that strongly interact with cells and cell-surface receptors to alter cell shape after metabolic interactions (active adhesion). In this paper, we briefly discuss the relationship between materials surface characteristics and cells for biomaterials designs in these categories. We have extensively investigated the thermoresponsive polymer, poly(N-isopropylacrylamide) (PIPAAm), as grafted surfaces allowing recovery of confluent cell monolayers as contiguous living cell sheets for tissue engineering applications. Cellular interactions with PIPAAm-grafted surfaces can be regulated vertically using the thickness of the PIPAAm-grafted layers in nanometer-scale levels, as well as laterally (spatially) using nano-patterned PIPAAm chemistry on various other surface chemistries. PIPAAm-grafted surfaces with 15-20-nm thick layers exhibit temperature-dependent cell adhesion/detachment control, while surfaces with PIPAAm layer thicknesses of more than 30 nm do not support cell adhesion. These changes in cell adhesion are explained by the limited mobility of the surface grafted polymer chains as a function of grafting, hydration, and temperature.

Animals↗
PubMed2004

Enhanced antitumor immunity derived from a novel vaccine of fusion hybrid between dendritic and engineered myeloma cells.

AIM: Dendritic cell-tumor cell fusion hybrid vaccines which facilitate antigen presentation represent a new powerful strategy in cancer immunotherapy. The clinical frequency of objective responses to the conventional fusion hybrid vaccines is still quite low, indicating that the current conventional protocol of simply fusing dendritic cells (DCs) and tumor cells needs further improvement to enhance its antitumor efficiency. METHODS: In the present study, we generated a novel fusion hybrid DC/J558(CD40L) by fusing DCs and an engineered J558(CD40L) myeloma cells expressing CD40 ligand (CD40L) molecule using polyethylene glycol (PEG). The fusion efficiency was approximately 20%. We investigated the antitumor immunity derived from vaccination of the fusion hybrid DC/J558(CD40L). RESULTS: Our results showed that vaccination of mice with DC/J558(CD40L) hybrids induced more efficient cytotoxic T lymphocyte (CTL) responses and protective immunity against J558 tumor cells, than that of the conventional fusion hybrid DC/J558 from the fusion of DCs and J558 tumor cells. The antitumor immunity derived from vaccination of DC/J558(CD40L) was mainly mediated by CD4(+) and CD(8+)cT cells, but not natural killer (NK) cells. CONCLUSION: Therefore, this novel fusion hybrid vaccine which combines gene-modified tumor and DC vaccines may be an attractive strategy for cancer immunotherapy.

Animals↗
PubMed2001

A tissue engineered cell-occlusive device for hard tissue regeneration--a preliminary report.

Tissue engineering is an emerging discipline that applies engineering principles to create devices for the study, restoration, modification, and assembly of functional tissues and organs from native or synthetic sources. In the field of guided bone regeneration (GBR), cellular matter engineering has been applied, more or less successfully, to the development of biodegradable and bioresorbable devices with chemical, physical, or mechanical properties, structure, or form that permit active tissue integration with desirable cell types and tissue components. The employment of synthetic and naturally occurring polymers as well as sophisticated manufacturing technologies allow the tissue engineering of matrix configurations so that the biophysical limitations of mass transfer can be satisfied. The configuration of such a hybrid matrix can also be manipulated to vary the surface area available for cell attachment, as well as to optimize the exposure of the attached cells to nutrients. A biodegradable and bioresorbable device made of synthetic and natural polymers was engineered specifically for GBR procedures. The degradation and resorption kinetics as well as the mechanical properties give the device the potential to function as a carrier for bone growth factors. This innovative device was applied as a GBR membrane in a clinical investigation in seven patients.

Absorbable Implants↗
PubMed1996

IL-12-engineered dendritic cells serve as effective tumor vaccine adjuvants in vivo.

The recent identification of tumor-associated antigens (TAA) and TAA-derived peptides presented by MHC molecules to T cells has provided the tools to design and test clinical vaccines for treating human malignancies, such as melanoma. While the most effective adjuvant for use in vaccine formulation remains unclear, autologous dendritic cells (DC) appear to be good candidate adjuvants. We have previously shown that syngeneic bone marrow-derived DC when pulsed ex vivo with relevant TAA-derived peptides can effectively vaccinate mice against a subsequent challenge with tumor or can effectively treat animals bearing established tumors. In this report, we have engineered murine interleukin-12 (mIL-12), a potent stimulator of cell-mediated immunity, into murine DC using retroviral-mediated or plasmid-based transfection procedures. Transfectants produced up to 25 ng rIL-12/10(6) cells/48 hours. These engineered cells are capable of promoting enhanced anti-tumor, antigen-specific CTL responses compared to nontransduced DC.

Adjuvants, Immunologic↗
PubMed2006

[The cell micro-encapsulation techniques and its advancement in the field of gene therapy].

It is no doubt that the gene therapy using recombinant engineering cells provides a novel approach to many refractory diseases. However, the transplant rejection from the host's immune system against heterogeneous cells has been the main handicap of its clinical application. The modern cell micro-encapsulation technique with good immune isolation makes it possible to overcome this problem and has shown potential application foreground in clinical therapies for a lot of diseases such as Parkinson's disease and Hemophiliac disease. This article reviews mainly the relative materials and techniques in processing micro-encapsulation, the host cells used to construct the recombinant genetic engineering cells and application of cell micro-encapsulation technique in the field of gene therapy.

Biomedical Engineering↗
PubMed2005

Tissue engineering, stem cells and cloning: current concepts and changing trends.

Organ damage or loss can occur from congenital disorders, cancer, trauma, infection, inflammation, iatrogenic injuries or other conditions and often necessitates reconstruction or replacement. Replacement may take the form of organ transplant. At present, there is a severe shortage of donor organs that is worsening with the aging of the population. Tissue engineering follows the principles of cell transplantation, materials science and engineering towards the development of biological substitutes that can restore and maintain normal tissue function. Therapeutic cloning involves the introduction of a nucleus from a donor cell into an enucleated oocyte to generate embryonic stem cell lines whose genetic material is identical to that of its source. These autologous stem cells have the potential to become almost any type of cell in the adult body, and thus would be useful in tissue and organ replacement applications. This paper reviews recent advances in stem cell research and regenerative medicine, and describes the clinical applications of these technologies as novel therapies for tissue or organ loss.

Animals↗
PubMed2000

Directed evolution of a stable scaffold for T-cell receptor engineering.

Here we have constructed a single-chain T-cell receptor (scTCR) scaffold with high stability and soluble expression efficiency by directed evolution and yeast surface display. We evolved scTCRs in parallel for either enhanced resistance to thermal denaturation at 46 degrees C, or improved intracellular processing at 37 degrees C, with essentially equivalent results. This indicates that the efficiency of the consecutive kinetic processes of membrane translocation, protein folding, quality control, and vesicular transport can be well predicted by the single thermodynamic parameter of thermal stability. Selected mutations were recombined to create an scTCR scaffold that was stable for over an hour at 65 degrees C, had solubility of over 4 mg ml(-1), and shake-flask expression levels of 7.5 mg l(-1), while retaining specific ligand binding to peptide-major histocompatibility complexes (pMHCs) and bacterial superantigen. These properties are comparable to those for stable single-chain antibodies, but are markedly improved over existing scTCR constructs. Availability of this scaffold allows engineering of high-affinity soluble scTCRs as antigen-specific antagonists of cell-mediated immunity. Moreover, yeast displaying the scTCR formed specific conjugates with antigen-presenting cells (APCs), which could allow development of novel cell-to-cell selection strategies for evolving scTCRs with improved binding to various pMHC ligands in situ.

Animals↗
PubMed1996

Human dendritic cells genetically engineered to express high levels of the human epithelial tumor antigen mucin (MUC-1).

We have achieved stable high-level expression of a human tumor antigen, epithelial cell mucin (MUC-1), on human dendritic cells (DCs) by retroviral transduction of CD34+ progenitor cells and their subsequent cytokine-induced differentiation into DCs. The process of retroviral transduction did not alter the growth or differentiation of DCs from CD34+ progenitor cells. Immunofluorescence and electron microscopy studies revealed that the expression of mucin was limited to the body of the DCs and was excluded from the cytoplasmic veils of the DCs. Furthermore, the expression of mucin on DCs was similar, if not identical, to the nonpolarized expression of mucin found on carcinoma cells. In functional studies, the MUC-1(+)-transduced DCs were potent stimulators of allogeneic CD4+ T cells and, in fact, were superior to MUC-1- DCs. Thus, MUC-1+ DCs are expected to be a valuable tool in the immunotherapeutic treatment of patients with tumors that express MUC-1.

Antigens, CD34↗
PubMed2002

Marked prolongation of cardiac allograft survival by dendritic cells genetically engineered with NF-kappa B oligodeoxyribonucleotide decoys and adenoviral vectors encoding CTLA4-Ig.

Bone marrow-derived dendritic cells (DCs) can be genetically engineered using adenoviral (Ad) vectors to express immunosuppressive molecules that promote T cell unresponsiveness. The success of these DCs for therapy of allograft rejection has been limited in part by the potential of the adenovirus to promote DC maturation and the inherent ability of the DC to undergo maturation following in vivo administration. DC maturation occurs via NF-kappaB-dependent mechanisms, which can be blocked by double-stranded "decoy" oligodeoxyribonucleotides (ODNs) containing binding sites for NF-kappaB. Herein, we describe the combined use of NF-kappaB ODNs and rAd vectors encoding CTLA4-Ig (Ad CTLA4-Ig) to generate stably immature murine myeloid DCs that secrete the potent costimulation blocking agent. These Ad CTLA4-Ig-transduced ODN DCs exhibit markedly impaired allostimulatory ability and promote apoptosis of activated T cells. Furthermore, administration of Ad CTLA4-Ig ODN-treated donor DCs (C57BL10; B10(H-2b)) before transplant significantly prolongs MHC-mismatched (C3HHeJ; C3H(H-2k)) vascularized heart allograft survival, with long-term (>100 days) donor-specific graft survival in 40% of recipients. The mechanism(s) responsible for DC tolerogenicity, which may involve activation-induced apoptosis of alloreactive T cells, do not lead to skewing of intragraft Th cytokine responses. Use of NF-kappaB antisense decoys in conjunction with rAd encoding a potent costimulation blocking agent offers promise for therapy of allograft rejection or autoimmune disease with minimization of systemic immunosuppression.

Abatacept↗
PubMed1991

Functional and immunological characterization of SIV envelope glycoprotein produced in genetically engineered mammalian cells.

Retroviral envelope glycoproteins interact with cell receptors and are targets for antiviral immune responses in infected hosts. Macaque simian immunodeficiency virus (SIVmac) is a T-lymphocytopathic lentivirus which causes an AIDS-like disease in rhesus macaques. The envelope gene of SIVmac encodes a precursor glycoprotein (gp160) which is cleaved into an external domain (gp130) and a transmembrane domain (gp32). To investigate the functional and immunological properties of the SIV external envelope glycoprotein, we have used genetically engineered mammalian cells to produce recombinant gp130 (rgp130). The rgp130 has the appropriate molecular weight, is glycosylated, and has native conformation as determined by binding to the cell receptor for SIV, the CD4 antigen. Rhesus macaques immunized with purified rgp130 formulated in muramyl dipeptide adjuvant generated high titers of antienvelope antibodies. Antibodies from these macaques were tested for in vitro virus neutralization; very low or undetectable levels of neutralization were observed. In contrast, neutralizing antibodies were readily detected in sera from goats immunized with rgp130. With respect to cell-mediated immunity, proliferative responses to rgp130 were demonstrated in peripheral blood monocyte cells (PBMC) from macaques immunized with the recombinant glycoprotein as well as in PBMC from SIV-infected animals. These results show that rgp130 is functional and immunogenic; the potential of rgp130 for protective immunization remains to be determined.

Animals↗
PubMed2006

Tissue engineered epithelial cell sheets for the creation of a bioartificial trachea.

To successfully engineer a bioartificial tracheal replacement, it is believed that the regeneration of a functional epithelial lining is a key requirement. In the present study, rabbit tracheal epithelial cells were cultured on temperature-responsive culture dishes, under normal culture conditions at 37 degrees C. By simple temperature reduction to 20 degrees C, the cultured epithelial cells were noninvasively harvested as intact sheets, without the use of any proteolytic enzymes. Support Dacron grafts that had been subcutaneously implanted for 4 weeks to allow for host tissue and vessel infiltration were then opened, and the tracheal epithelial cell sheets were transplanted to the luminal surface without sutures. These fabricated constructs were then used as tracheal replacements, in a rabbit model. Four weeks after transplantation, results showed that the tracheal grafts were covered by a mature, pseudostratified columnar epithelium. In contrast, control constructs that did not receive cell sheet transplantation demonstrated only a thin, immature epithelium at the center of the replacement graft. These results therefore demonstrate that these tracheal epithelial cell sheets can create an epithelial lining on the luminal surface of a bioartificial trachea.

Animals↗
PubMed2003

Cells over-expressing EAAT2 protect motoneurons from excitotoxic death in vitro.

Amyotrophic lateral sclerosis is an incurable disease in which cerebral and spinal motoneurons degenerate, causing paralysis and death within 2-5 years. One of the pathogenic factors of motoneuron death is a chronic excess of glutamate, which exceeds its removal by astrocytes, i.e. excitotoxicity. Extra glutamate uptake in the spinal cord may slow down or prevent motoneuron death. We have engineered cells over-expressing the main glutamate transporter and tested their potential to rescue motoneurons exposed to high levels of glutamate in vitro. The engineered cells protected motoneurons in a motoneuron-astrocyte co-culture at glutamate concentrations when astrocytes were no longer capable of removing glutamate. This suggests that engineered cells, introduced into the spinal column, can help remove glutamate, thereby preventing motoneuron death.

Animals↗