Targeted Cell Reprogramming Produces Analgesic Chromaffin-Like Cells from Human Mesenchymal Stem Cells

Cell Transplantation

Article

W. M. Duan¹  H. N. Yang²  K. Ma³  G. Shi³  T. Qu³  G. D. Pappas³ 

[1] Department of Anatomy, Capital Medical University, Youanmenwai, Fengtai District, Beijing, China;Department of Neural Medicine, The Second Hospital of Shandong University, Jinan, Shandong, China;Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA;

关键词: Mesenchymal stem cells;    Adrenal chromaffin cells;    Cell reprogramming;    Pain management;    Autologous stem cells;   

DOI  :  10.3727/096368912X662435

 received in 2012-03-29, accepted in 2012-11-10,  发布年份 2013

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2013 Cognizant Comm. Corp.

【 图 表 】

Figure 10.