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At least 37 records · Page 2Linked to original sources
PubMed2002

The future of reproductive cellular engineering in male infertility.

Understanding of the pathophysiology of defective spermatogenesis, spermatozoa, and germ cell function must be advanced so that appropriate rational treatment, such as gene therapy, can be developed. Despite the dramatic advances in ART, one ultimate goal must be to develop treatment so that the couple can conceive naturally. Because such treatment will not be possible in all cases, a complementary step will be the ability to induce the production of haploid, functionally competent germ cells that can be used for ART. The achievement of these goals will be based on advances in many other disciplines. Whatever the future holds, it promises to be exciting.

Biomedical Engineering↗
PubMed1999

Evaluation of protein-modulated macrophage behavior on biomaterials: designing biomimetic materials for cellular engineering.

Macrophage is a central cell type in directing host inflammatory and immune processes; hence, its response to biomaterials (i.e. adhesion and giant cell formation) has a direct impact on material biostability and biocompatibility. In this paper, several in vitro and in vivo techniques from previously published results and current investigations are highlighted and presented to demonstrate means of delineating a part of the complex molecular mechanisms involved in the interaction between biomaterials and macrophages. Complement component C3 was found critical in mediating the initial adhesion of human macrophages on medical-grade polyetherurethaneureas. From radioimmunoassay studies, the presence of a diphenolic antioxidant additive in polyetherurethaneureas increased the propensity for complement upregulation but did not affect adherent macrophage density. The subcutaneous cage-implant system was utilized to confirm the role of interleukin-4 in the fusion of adherent macrophages to form foreign body giant cells on polyurethanes in vivo. To probe the function-structural relationship of macrophage-active proteins, fibronectin was employed as a model in the formulation of synthetic oligopeptide mimetics. Peptides were grafted onto previously developed, non-cell adhesive polyethyleneglycol-based networks. The results indicate that grafted tripeptide RGD sequence supported higher adherent macrophage density than surfaces grafted with other peptides such as PHSRN and PRRARV sequences. However, the formation of foreign body giant cells on peptide-grafted networks was highly dependent on the relative orientation between PHSRN and RGD sequences located in a single peptide.

Biocompatible Materials↗
PubMed2002

Apoptosome: the cellular engine for the activation of caspase-9.

Characterization of the apoptosome by cryo-EM reveals a wheel-shaped heptameric assembly involving Apaf-1 and cytochrome c. This structure provides a framework for understanding the activation mechanisms of caspase-9, an important initiator caspase in apoptosis.

Apoptosis↗
PubMed2001

Cellular engineering: molecular repair of membranes to rescue cells of the damaged nervous system.

PURPOSE: The acute administration of hydrophilic polymers (polyethylene glycol) can immediately seal nerve membranes, preventing their continuing dissolution and secondary axotomy. Polymer application can even be used to reconnect, or fuse, the proximal and distal segments of severed axons in completely transected adult mammalian spinal cord. CONCEPT: The sealing or fusion of damaged nerve membranes leads to a very rapid (minutes or hours) recovery of excitability in severely damaged nerve fibers, observed as a rapid return of nerve impulse conduction in vitro, as well as an in vivo recovery of spinal cord conduction and behavioral loss in spinal cord-injured adult guinea pigs. RATIONALE: Surfactant application produces a rapid repair of membrane breaches through mechanisms of interaction between the polymers and the aqueous phase of damaged membranes, and their ability to insert into, or seal, the hydrophobic core of the axolemma exposed by mechanical damage. DISCUSSION: This new technology applied to severe neurotrauma offers a clinically safe and practical means to rescue significant populations of spinal cord nerve fibers within 8 hours after damage--preventing their continued dissolution and secondary axotomy by secondary injury mechanisms. Application of this novel technology to other injuries to the peripheral and central nervous system is discussed, as well as a general application to soft tissue trauma.

Animals↗
PubMed1994

Cellular engineering and gene therapy strategies for insulin replacement in diabetes.

In diabetes, insulin secretion is either completely absent (insulin-dependent diabetes mellitus [IDDM]) or inappropriately regulated (non-insulin-dependent diabetes mellitus [NIDDM]). In recent years, new insights into the molecular and biochemical mechanism(s) of fuel-mediated insulin release coupled with advances in gene transfer technology have led to the investigation of molecular strategies for replacement of normal insulin delivery function. Such initiatives have included attempts to engineer glucose-stimulated insulin secretion in cell lines that might serve as surrogates for islets in IDDM. The development of DNA virus gene transfer systems of remarkable efficiency also has suggested ways in which the beta-cell dysfunction of NIDDM might ultimately be repaired by gene therapy. The emerging work in these areas and implications for the future are summarized in this perspective.

Cell Line↗
PubMed1989

Biotechnology of plasma proteins. Fractionation and applications.

Without discussing all of the current problems of industrial plasma fractionation, this INSERM International Symposium emphasized the importance of the technological progress of the last ten years. Although Cohn's classical technique of alcohol precipitation is still the most widely used, new techniques are rapidly being developed based on more selective methods with high extraction yields. However, it is certain that, given the growth in biotechnologies with the industrial applications of genetic engineering and cellular engineering, various problems will eventually be raised concerning plasma fractionation. It is probable that in the relatively near future certain fractions such as F VIII will no longer be prepared from plasma; but can the other fractions be reasonably replaced in the foreseeable future? Furthermore, the problems of purification will always be the crux of the development of biotechnologies. The technical committee of the OECD has recently drawn the attention of European governments to the considerable importance for the future of bioindustries of 'downstream processings' and the need to develop research on methods of extraction and purification. Human plasma is certainly the ideal model for the development of new methods of protein purification which could subsequently be applied to other industrial fields such as cellular engineering or genetic engineering. European countries definitely have an edge in this field as a result of their industries and fractionation centers.

Biotechnology↗
PubMedDate not supplied

A genetically engineered, nonthrombogenic cellular lining for LVADs: in vitro preconditioning before in vivo implantation.

Because of the clinical success of left ventricular assist devices (LVADs) used for short-term "bridge to transplant" and the limited availability of donor organs, heart assist devices are being considered for long-term implantation as an alternative to heart transplantation. In an effort to improve biocompatibility, our laboratory has developed a nonthrombogenic cellular lining from genetically engineered smooth muscle cells (GE-SMC) for the Thermocardiosystems Heartmate LVAD. Smooth muscle cells have been transduced with the gene for endothelial nitric oxide synthase (NOS III) and produce NO at concentrations that reduce platelet deposition and smooth muscle cell proliferation when tested in vitro. In this investigation, the adhesive capabilities of GE-SMC linings were examined. An in vitro circulatory loop was designed to expose cell lined LVADs to in vivo operating conditions. Cumulative cell loss from cell lined LVADs was less than 10% after 24 hours of flow. Using a protocol for "preconditioning" the cell lining within the mock circulatory loop, the first implantation of an LVAD containing a genetically engineered SMC lining was successfully implemented in a bovine model. Results from this 24 hour study indicate that the flow-conditioned cellular lining remained intact with no evidence of thromboembolization and only minimal changes in coagulation studies.

Animals↗
PubMed2001

[Assembly and evaluation of tissue engineered human cellular alveolar bony implanting materials in vitro].

OBJECTIVE: To assembly human cellular alveolar bony implanting materials in vitro and evaluate their osteogenic activities. METHODS: Human alveolar bone cells were separated from alveolar bone around the third impacted teeth of 3 patients by enzyme digestion and cultured in alpha-MEM containing beta-glycerophosphate and Dexamethasone at 5% CO2, 37 degrees C for 21-28 days. Confirmed osteoblasts-like cells were then seeded onto 3 kinds of degradable biomaterials of polyglycolic acid scaffold, collagen sponge, and L-lactic acid/epsilon-caprolactone to form the cell-scaffold complexes. The 3 types of complexes were continued to culture for 21-28 days at the same conditions. The cell proliferation, morphological changes, ALPase activity and mineral nodule formation on scaffolds were measured and observed at 3 days intervals. RESULTS: The results indicated that the cultured human alveolar bone origin cells from 3 patients could successfully express the osteoblasts phenotype in single layered culturing after stimulated by beta-glycerophosphate and Dexamethasone. The cultured osteoblast-like cells seeded on PGAS matrix had the highest attachment, proliferative and osteogenic activities, suggesting a good bio-affinity between the human alveolar osteoblast-like cells and the PGAS matrix. The statistical analysis (ANOVA) showed that there were significant differences between PGAS- osteoblasts complex and CLGS or LACT complexes on osteogenic activities (P < 0.05). CONCLUSION: PGAS-osteoblast complex is worth to be further developed into a tissue-engineered cellular artificial bony implant for reconstructing the oral-maxillofacial bony defects.

Absorbable Implants↗
PubMed2007

Permeability issues in whole-cell bioprocesses and cellular membrane engineering.

Nutrient uptake and waste excretion are among the many important functions of the cellular membrane. While permitting nutrients into the cell, the cellular membrane system evolves to guide against noxious agents present in the environment from entering the intracellular milieu. The semipermeable nature of the membrane is at odds with biomolecular engineers in their endeavor of using microbes as cell factory. The cellular membrane often retards the entry of substrate into the cellular systems and prevents the product from being released from the cellular system for an easy recovery. Consequently, productivities of whole-cell bioprocesses such as biocatalysis, fermentation, and bioremediations are severely compromised. For example, the rate of whole-cell biocatalysis is usually 1-2 orders of magnitude slower than that of the isolated enzymes. When product export cannot keep pace with the production rate, intracellular product accumulation quickly leads to a halt of production due to product inhibition. While permeabilization via chemical or physical treatment of cell membrane is effective in small-scale process, large-scale implementation is problematic. Molecular engineering approach recently emerged as a much better alternative. Armed with increasingly sophisticated tools, biomolecular engineers are following nature's ingenuity to derive satisfactory solutions to the permeability problem. This review highlights these exciting molecular engineering achievements.

Biodegradation, Environmental↗