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: Chromaffin cell transplants have been explored since the early 1980´s as a promising alternative in different pathological states, mainly Parkinson disease and chronic pain. Advances are significant since transplants have been performed in humans. The general mechanism of these transplants relies in the capacity of chromaffin cells to act as mini-pumps that release amines and peptides. Different strategies are being used to improve the efficacy of transplants. However, a remaining hurdle is to determine the viability across time and the interaction with the microenvironment of the graft. We analyzed previous and current results finding that although there is a lot of positive evidence, also there is a lack of molecular studies that support behavioral results. The present review gives an update on recent advances of chromaffin cell transplants and their future in the clinic.Life sciences 10/2012; · 2.56 Impact Factor
Dataset: Targeted therapies for pain 2011
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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; · 4.42 Impact Factor