In Vitro Cellular & Developmental Biology - Animal

, Volume 48, Issue 9, pp 562–569

Exploring the enkephalinergic differentiation potential in adult stem cells for cell therapy and drug screening implications


DOI: 10.1007/s11626-012-9546-4

Cite this article as:
Hafizi, M., Bakhshandeh, B., Soleimani, M. et al. In Vitro Cell.Dev.Biol.-Animal (2012) 48: 562. doi:10.1007/s11626-012-9546-4


Stem cell therapy is one of the most promising treatments in neuroregenerative medicine. Considering the role of the endogenous opioid system in controlling the pathophysiology of neurological disorders and behavioral aberrations, current studies have focused on enkephalins as a part of the opioid system. Due to high capability of unrestricted somatic stem cells (USSCs) and human mesenchymal stem cells (hMSCs) for cell therapy and transplantation; here, we examined their enkephalinergic differentiation potential through Ikaros-related pathways in order to develop in vitro models to help drug screening and stem cell therapy for the opioid-related disorders. The authenticity of the stem cells was verified by differentiation experiments along with flow cytometry for surface markers. Later, we confirmed their neurogenic differentiation with semiquantitative and quantitative transcriptional and translational evaluations of the enkephalinergic-related genes such as proenkephalin, CREBZF, Ikaros, and prodynorphin. Our findings supported the enkephalinergic differentiation of these stem cells. Noteworthy, USSCs showed higher potential for differentiating into enkephalinergic neurons under Ikaros activation than hMSCs, which makes them appropriate for neurological therapeutic applications. In conclusion, this study suggests a powerful in vitro model for neurogenesis that may help clarification of enkephalinergic differentiation and related signaling networks along with neural drug screening. Such investigations may be beneficial to ameliorate the neural-related therapeutic approaches.


Unrestricted somatic stem cellsHuman mesenchymal stem cellsEnkephalinergic differentiationDrug screeningCell therapy

Supplementary material

11626_2012_9546_Fig8_ESM.jpg (76 kb)
Figure 1

Osteogenic (Alizarin Red), Adipogenic (Oil Red), and chondrogenic (Alcian Blue) differentiation of stem cells after 21 d of in vitro induction. Bars 100 μm (JPEG 75 kb)

11626_2012_9546_MOESM1_ESM.tif (6.2 mb)
High-resolution image file (TIFF 6,355 kb)

Copyright information

© The Society for In Vitro Biology 2012

Authors and Affiliations

  1. 1.Stem Cell Biology DepartmentStem Cell Technology Research CenterTehranIran
  2. 2.Department of Biotechnology, College of ScienceUniversity of TehranTehranIran
  3. 3.Department of Hematology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran