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      • Record: found
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      Review of the History and Current Status of Cell-Transplant Approaches for the Management of Neuropathic Pain

      review-article

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          Abstract

          Treatment of sensory neuropathies, whether inherited or caused by trauma, the progress of diabetes, or other disease states, are among the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord would be the logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the transplant of cells or a cell line to treat human disease. The history of the research and development of useful cell-transplant-based approaches offers an understanding of the advantages and problems associated with these technologies, but as an adjuvant or replacement for current pharmacological treatments, cell therapy is a likely near future clinical tool for improved health care.

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          Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.

          L A Greene, A Tischler (1976)
          A single cell clonal line which responds reversibly to nerve growth factor (NGF) has been established from a transplantable rat adrenal pheochromocytoma. This line, designated PC12, has a homogeneous and near-diploid chromosome number of 40. By 1 week's exposure to NGF, PC12 cells cease to multiply and begin to extend branching varicose processes similar to those produced by sympathetic neurons in primary cell culture. By several weeks of exposure to NGF, the PC12 processes reach 500-1000 mum in length. Removal of NGF is followed by degeneration of processes within 24 hr and by resumption of cell multiplication within 72 hr. PC12 cells grown with or without NGF contain dense core chromaffin-like granules up to 350 nm in diameter. The NGF-treated cells also contain small vesicles which accumulate in process varicosities and endings. PC12 cells synthesize and store the catecholamine neurotransmitters dopamine and norepinephrine. The levels (per mg of protein) of catecholamines and of the their synthetic enzymes in PC12 cells are comparable to or higher than those found in rat adrenals. NGF-treatment of PC12 cells results in no change in the levels of catecholamines or of their synthetic enzymes when expressed on a per cell basis, but does result in a 4- to 6-fold decrease in levels when expressed on a per mg of protein basis. PC12 cells do not synthesize epinephrine and cannot be induced to do so by treatment with dexamethasone. The PC12 cell line should be a useful model system for neurobiological and neurochemical studies.
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            Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58 transgenic mouse.

            D Kioussis, N Yannoutsos, Mogens L Larsen … (1991)
            Studies on cell lines have greatly improved our understanding of many important biological questions. Generation of cell lines is facilitated by the introduction of immortalizing oncogenes into cell types of interest. One gene known to immortalize many different cell types in vitro encodes the simian virus 40 (SV40) large tumor (T) antigen (TAg). To circumvent the need for gene insertion in vitro to generate cell lines, we created transgenic mice harboring the SV40 TAg gene. Since previous studies have shown that TAg expression in transgenic mice is associated with tumorigenesis and aberrant development, we utilized a thermolabile TAg [from a SV40 strain, tsA58, temperature sensitive (ts) for transformation] to reduce the levels of functional TAg present in vivo. To direct expression to a broad range of tissues, we used the mouse major histocompatibility complex H-2Kb promoter, which is both widely active and can be further induced by interferons. tsA58 TAg mRNA was expressed in tissues of all animals harboring the hybrid construct. Development of all tissues was macroscopically normal except for thymus, which consistently showed hyperplasia. Fibroblast and cytokeratin+ thymic epithelial cultures from these mice were readily established without undergoing crisis and were conditionally immortal in their growth; the degree of conditionality was correlated with the levels of tsA58 TAg detected. One strain of H-2Kb-tsA58 mice has been bred through several generations to homozygosity and transmits a functional copy of the transgene.
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              A shared vesicular carrier allows synaptic corelease of GABA and glycine.

              Sonja M Wojcik, Shutaro Katsurabayashi, Isabelle Guillemin … (2006)
              The type of vesicular transporter expressed by a neuron is thought to determine its neurotransmitter phenotype. We show that inactivation of the vesicular inhibitory amino acid transporter (Viaat, VGAT) leads to embryonic lethality, an abdominal defect known as omphalocele, and a cleft palate. Loss of Viaat causes a drastic reduction of neurotransmitter release in both GABAergic and glycinergic neurons, indicating that glycinergic neurons do not express a separate vesicular glycine transporter. This loss of GABAergic and glycinergic synaptic transmission does not impair the development of inhibitory synapses or the expression of KCC2, the K+ -Cl- cotransporter known to be essential for the establishment of inhibitory neurotransmission. In the absence of Viaat, GABA-synthesizing enzymes are partially lost from presynaptic terminals. Since GABA and glycine compete for vesicular uptake, these data point to a close association of Viaat with GABA-synthesizing enzymes as a key factor in specifying GABAergic neuronal phenotypes.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pain Res Treat
                Journal ID (iso-abbrev): Pain Res Treat
                Journal ID (publisher-id): PRT
                Title: Pain Research and Treatment
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-1542
                ISSN (Electronic): 2090-1550
                Publication date (Print): 2012
                Publication date (Electronic): 14 June 2012
                Volume: 2012
                Electronic Location Identifier: 263972
                Affiliations
                1Miami VA Health System Center, D806C, 1201 NW 16th Street, Miami, FL 33125, USA
                2Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
                3Department of Neurosurgery, Tripler Army Medical Center, 1 Jarrett White Road, Honolulu, HI 96859, USA
                4The Miami Project to Cure Paralysis, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
                Author notes

                Academic Editor: Steve McGaraughty

                Article
                DOI: 10.1155/2012/263972
                PMC ID: 3382629
                PubMed ID: 22745903
                SO-VID: d51f046e-93dd-44d7-877e-02e16abf5ac9
                Copyright © Copyright © 2012 Mary J. Eaton et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 8 March 2012
                Date accepted : 9 April 2012
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Anesthesiology & Pain management
                Data availability:
                ScienceOpen disciplines: Anesthesiology & Pain management

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