Targeted cell reprogramming produces analgesic chromaffin-like cells from human mesenchymal stem cells

Cell Transplant. 2013;22(12):2257-66. doi: 10.3727/096368912X662435. Epub 2013 Feb 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Analgesics / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology
  • Cell Extracts / pharmacology
  • Cells, Cultured
  • Cellular Reprogramming
  • Chromaffin Cells / chemistry
  • Chromaffin Cells / metabolism
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Pain / metabolism
  • Pain / pathology
  • Pain / surgery*
  • Rats
  • Rats, Sprague-Dawley
  • Swine
  • Transplantation, Autologous
  • Young Adult

Substances

  • Analgesics
  • Biomarkers
  • Cell Extracts