One-year chromaffin cell allograft survival in cancer patients with chronic pain: morphological and functional evidence.
ABSTRACT The control of chronic pain through transplantation of chromaffin cells has been reported over the past few years. Analgesic effects are principally due to the production of opioid peptides and catecholamines by chromaffin cells. Clinical trials have been reported with allografts consisting of whole-tissue fragments implanted into the subarachnoid space of the lumbar spinal cord (14,19,36). In the present study, allogeneic grafts were successfully used to control chronic pain in two patients over a period of 1 yr based on patient reported pain scores, morphine intake, and CSF levels of Met-enkephalin. Macroscopic examination at autopsy located the transplanted tissue fragments in the form of multilobulated nodules at the level of the spinal axis and cauda equina. Immunocytochemical microscopy showed neuroendocrine cells are positive for chromagranin A (CGA), and enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbetaH). The results suggest that there is a relationship between analgesic effect, Met-enkephalin levels in CSF, and the presence of chromaffin cells surviving in spinal subarachnoid space.
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ABSTRACT: Transplantation of allogeneic adrenal chromaffin cells demonstrated the promise of favorable outcomes for pain relief in patients. However, there is a very limited availability of suitable human adrenal gland tissues, genetically well-match donors in particular, to serve as grafts. Xenogeneic materials, such as porcine and bovine adrenal chromaffin cells, present problems, for instance, immune rejection and possible pathogenic contamination. To overcome these challenges, we have tested the novel approach of cell reprogramming to reprogram human bone marrow (BM)-derived mesenchymal stem cells (hMSCs) using cellular extracts of porcine chromaffin cells and we produced a new type of cells, chromaffin-like cells. These chromaffin-like cells generated from the reprogrammed hMSCs displayed a significant increase in expression of human preproenkephalin (hPPE), a precursor for enkephalin opioid peptides, compared to the inherent expression of hPPE in naïve hMSCs. The resultant chromaffin-like cells not only expressed the key molecular markers of adrenal chromaffin cells, such as tyrosine hydroxylase (TH) and methionine enkephalin (Met-enkephalin), but also secreted opioid peptide Met-enkephalin in culture. In addition, intrathecal injection of chromaffin-like cells in rats produced significant analgesic effects without using immunosuppressants. These results suggest that analgesic chromaffin-like cells can be produced from an individual's own tissue-derived stem cells by targeted cell reprogramming and also that these chromaffin-like cells may serve as potential autografts for chronic pain management.Cell Transplantation 02/2013; 22(12). DOI:10.3727/096368912X662435 · 3.57 Impact Factor
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ABSTRACT: A CO2 capture and storage (CCS) retrofit strategy is compared to several repowering strategies for decarbonising existing coal power plant sites. The more promising repowering approaches analyzed seem to be a shift to natural gas via natural gas combined cycles and deployment of systems that coproduce synthetic liquid fuels plus electricity from coal and biomass with CCS. Under a wide range of plausible conditions, the latter option seems to the most promising approach for decarbonising these plant sites—exploiting simultaneously the carbon mitigation benefit of coprocessing biomass in CCS energy systems and the more general benefits offered by coproduction systems with CCS of: (i) low CO2 capture costs, (ii) high efficiency of power generation, and (iii) large credits for the sale of the synfuel coproducts at current or higher oil prices, and (iv) very low minimum dispatch costs.Energy Procedia 01/2011; 4:1843-1850. DOI:10.1016/j.egypro.2011.02.062
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ABSTRACT: Cellular transplantation is a potentially powerful approach for the alleviation of chronic pain. The strategy of cell transplantation for the treatment of pain is focused on cell-based analgesia and neural repair. (1) Adrenal medullary chromaffin cells and the PC12 cell line have been used to treat cancer pain and neuropathic pain in both animal models and human cases. As biological or living minipumps, these cells produce and secrete pain-reducing neuroactive substances if administered directly into the spinal subarachnoid space. (2) Cell implantation for pain neurorestorative therapy is a new concept and emerging research field for pain control along with neural repair. Possible neurorestorative mechanisms include neuroprotective, neurotrophic, neuroreparative, neuroregenerative, neuromodulation or neuroconstructive interventions, as well as immunomodulation and enhancing the microcirculation. These factors may ultimately restore the damaged or irritated condition of the lesioned nerves. The growing preclinical and clinical data show that neural stem / progenitor cells, olfactory ensheathing cells, mesenchymal stromal cells, and CD34⁺ cells have the capacity to manage intractable pain and improve neurological functions. Cell delivery routes include local, intrathecal or intravascular implants. Although these strategies are still in their infancy phase for Pain Neurorestoratology, cell-based therapies could open up new avenues for the relief of pain. In this review these aspects are critically analyzed based on our own investigations.Cell Transplantation 08/2013; 22(1). DOI:10.3727/096368913X672091 · 3.57 Impact Factor