Adrenal medullary explants as an efficient tool for pain control: Adhesivebiomolecular components are involved in graft function ex vivo

Adrenal medullary (AM) tissue transplantation into the central nervous syst em has been reported as a potential source of opioid peptides and catechola mines, which have analgesic effects useful in the control of chronic pain, Clinical trials, involving allogeneic graft of whole tissue explants into t he subarachnoid space of the lumbar spinal cord, have already been reported . The aim of the present study was to determine whether adhesion and functi on of AM explants were related in some extent and how this relationship cou ld account for improvement of AM tissue in terms of analgesic activity befo re grafting. Our experiments demonstrated a significant correlation between the adherent state of AM organoids during culture and a sustained secretio n of Met-enkephalin and catecholamines by chromaffin cells (CC). These find ings suggest that optimal culture condition for AM organoid adhesion can be defined for maintenance of tissue, prior to transplantation. Using immunoc ytochemistry, flow cytometry, and ELISA assays we showed that different cel l adhesion molecules (CAMs) and extracellular matrix ECM proteins were expr essed and released by AM cells during culture, Adherent AM organoids expres sed increased levels of specific neural CAMs (NCAM and HNK-1 epitope) and i ntegrin chains (beta 1, alpha 1, alpha 2, alpha 4, alpha 5) and deposited m arkedly higher levels of fibronectin, but also laminin and collagen IV, Tho se molecules and probably adhesion processes they control might be involved in the maintenance of the CC-secreting neuroendocrine phenotype through ce llular signaling pathways, (C) 2000 Academic Press.