title: Targeted cell reprogramming produces analgesic chromaffin-like cells from human mesenchymal stem cells.
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-matched 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 are potential issues. 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. We produced a new type of cell, chromaffin-like cells, generated from the reprogrammed hMSCs, which displayed a significant increase in expression of human preproenkephalin (hPPE), a precursor for enkephalin opioid peptides, compared to the inherent expression of hPPE in naive 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.
authors: Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors: T
authors: T
authors: Qu
authors: G
authors: G
authors: Shi
authors: K
authors: K
authors: Ma
authors: H N
authors: HN
authors: Yang
authors: W M
authors: WM
authors: Duan
authors: G D
authors: GD
authors: Pappas
mesh_terms: D000328:Adult; D000700:Analgesics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002457:Cell Extracts / Q000494:pharmacology; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D019439:Chromaffin Cells / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010146:Pain / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D000700:Analgesics; D015415:Biomarkers; D002457:Cell Extracts