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PubMedDate not supplied

Transplants of neuronal cells bioengineered to synthesize GABA alleviate chronic neuropathic pain.

The use of cell lines utilized as biologic "minipumps" to provide antinociceptive molecules, such as GABA, in animal models of pain is a newly developing area in transplantation biology. The neuronal cell line, RN33B, derived from E13 brain stem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat GAD67 cDNA (glutamate decarboxylase, the synthetic enzyme for GABA), and the GABAergic cell line, 33G10.17, was isolated. The 33G10.17 cells transfected with the GAD67 gene expressed GAD67 protein and synthesized low levels of GABA at permissive temperature (33 degrees C), when the cells were proliferating, and increased GAD67 and GABA during differentiation at nonpermissive temperature (39 degrees C) in vitro, because GAD67 protein expression was upregulated with differentiation. A control cell line, 33V1, transfected with the vector alone, contained no GAD67 or GABA at either temperature. These cell lines were used as grafts in a model of chronic neuropathic pain induced by unilateral chronic constriction injury (CCI) of the sciatic nerve. Pain-related behaviors, including cold and tactile allodynia and thermal and tactile hyperalgesia, were evaluated after CCI in the affected hind paw. When 33G10.17 and 33V1 cells were transplanted in the lumbar subarachnoid space of the spinal cord 1 week after CCI, they survived greater than 7 weeks on the pia mater around the spinal cord. Furthermore, the tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI was significantly reduced during the 2-7-week period after grafts of 33G10.17 cells. The maximal effect on chronic pain behaviors with the GABAergic grafts occurred 2-3 weeks after transplantation. Transplants of 33V1 control cells had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that a chronically applied, low local dose of GABA presumably supplied by transplanted cells near the spinal dorsal horn was able to reverse the development of chronic neuropathic pain following CCI. The use of neural cell lines that are able to deliver inhibitory neurotransmitters, such as GABA, in a model of chronic pain offers a novel approach to pain management.

Animals↗
PubMed1996

Detection of antibodies against foot-and-mouth disease virus using a liquid-phase blocking sandwich ELISA (LPBE) with a bioengineered 3D protein.

A liquid-phase blocking sandwich enzyme-linked immunosorbent assay (ELISA-3D) was developed to detect specific antibodies to the 3D protein in sera from foot-and-mouth disease (FMD) virus (FMDV)-infected animals. The assay uses a nonstructural 3D recombinant protein and two polyclonal antisera, one for capture (bovine) and the other for detector (guinea pig). The specificity of the assay was demonstrated by negative results with 101 sera of cattle from the FMD-free zone in Argentina and with bovine and porcine sera raised against various RNA and DNA viruses. The ELISA-3D was able to detect antibodies in cattle after natural or experimental infection with FMDV of A, O, or C types as early as 5 days postinfection and at later stages in persistently infected animals. Comparison of the results with those obtained with the routinely used agar gel immunodiffusion test and a previously described ELISA, both employing a partially purified virus-infection-associated antigen, shows that the ELISA-3D is highly sensitive and specific and gives reproducible results. Its use as a tool for monitoring viral activity and for certification of FMDV-free animals is recommended.

Animals↗
PubMed2002

Biointerventional cardiology: the future interface of interventional cardiovascular medicine and bioengineering.

Major advances in cardiovascular intervention for chronic disease are underway. These innovations lie at the interface of minimally invasive catheter-based technologies and biologic approaches for the management of complex cardiovascular diseases. This review highlights key areas where such 'biointerventional' cardiovascular therapies are envisioned to occur: cardiac cell transplantation, myocardial gene therapy, genetic and photodynamic endovascular interventions, and vascular tissue engineering.

Biomedical Engineering↗
PubMed1991

Bioengineering activities at the New York Orthopaedic Hospital Research Laboratory.

The studies described above are representative of the Laboratory's long-standing dedication to the philosophy of multi-disciplinary research. Results from these studies will continue to provide new insights as to the function of diarthrodial joints, articular cartilage and other hydrated soft tissues. It appears reasonable to expect that in the years ahead we will have a better understanding of the mechanisms behind histomorphogenesis, growth, functional adaptation, regeneration, ageing and degeneration of connective tissues and osteoarthritis resulting from these investigations being conducted at the New York Orthopaedic Hospital Research Laboratory.

Biomechanical Phenomena↗
PubMed2002

Stem Cell Plasticity and Tissue Bioengineering: Great Expectations and Some Concerns.

"Stem cells" are by definition cells that self-renew and that have the capacity to differentiate into several lineages. A recent series of studies has challenged fundamental concepts of stem cell biology by suggesting that the functional potential of stem cells is not restricted to the tissue source from which they are derived. The ability for cells of one tissue to produce cells of other developmentally unrelated tissues has been defined as cellular plasticity. Therefore, the utility of stem cell plasticity in cell replacement therapy should be unlimited. Multipotent stem cells may be used to develop replacement tissues for congenital or degenerative disorders, either on their own or in combination with other therapeutic approaches such us gene therapy. There are, however, several concerns regarding the concept of stem cell plasticity and the methods used to evaluate the starting population. (c) 2002 Prous Science. All rights reserved.

Journal Article↗
PubMed1996

Bioengineering: alpha 1-proteinase inhibitor site-specific mutagenesis. The prospect for improving the inhibitor.

alpha 1-Proteinase inhibitor (alpha 1-PI) augmentation therapy has been licensed for treatment of alpha 1-PI-deficient individuals with pulmonary emphysema. The currently available product is purified from pooled human plasma. To obtain larger amounts of protein free from possible unknown plasma contaminants, human alpha 1-PI has been produced by recombinant DNA. Since wild-type alpha 1-PI is susceptible to oxidative impairment, several alpha 1-PI variants in which the active site oxidation-sensitive residue is replaced by inert residues have been constructed. This article is aimed at reviewing the history, biological efficacy, advantages, disadvantages, and concerns linked to alpha 1-PI recombinant DNA and site-specific mutagenesis technology.

Humans↗