No Detection of Potential Cancer Risk for Free-Viral Reprogrammed Stem Cell-Derived Dopaminergic Neurons from Adult Mice FibroblastsLiu G*
Department of Neuroscience, Carleton University, Ontario, Canada
- *Corresponding Author:
- Gele Liu, MD, PhD
Department of Neuroscience, 327 Life Sciences Research Building
Carleton University, 1125 Colonel by Drive
Ottawa, Ontario, K1S 5B6, Canada
Tel: 1613 520 2600
E-mail: [email protected]
Received date: January 27, 2015; Accepted date: June 03, 2015; Published date: June 05, 2015
Citation: Liu G (2015) No Detection of Potential Cancer Risk for Free-Viral Reprogrammed Stem Cell-Derived Dopaminergic Neurons from Adult Mice Fibroblasts. J Stem Cell Res Ther 5:286. doi:10.4172/2157-7633.1000286
Copyright: © 2015 Liu G This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Stem cell replacement therapy through the reprogramming of somatic cells is a significant prospective therapy for neurodegenerative diseases and personalized medicine. As virus-carrying reprogramming genes impart a considerable risk for tumor formation, current approaches tend to replace the viral pattern with a non-viral system. However, there is still great concern regarding the oncogenic properties of these reprogramming genes. At present no direct evidence can verify that non-viral systems do not influence genomic DNA integration and mutagenesis events in the final products after reprogramming.
Methods: We evaluated the potential cancer risk of reprogrammed stem cell-derived dopaminergic neurons using a unique non-viral vector containing four reprogramming genes. Reprogrammed stem cell-derived dopaminergic neurons were the final products after 50 days of cell culture from adult mice fibroblasts. After 6 months of culture, these cells were assessed for cancer risk.
Results: Overall cancer risk assessments were first examined using multiple stem cell biomarkers. We did not detect any overexpression of these biomarkers. Moreover, we assessed whether or not the most important neurotransmission factors were expressed after 6 months in mass cell culture. Our results determined that only robust gene expression of tyrosine hydroxylase (TH), as the rate-limiting enzyme in dopamine synthesis, was detected. Furthermore, the final product of TH-positive dopaminergic neurons was confirmed by sequencing TH genomic DNA. Our data suggested that none of the four reprogramming genes integrated into the host cell’s genomic DNA and that no other mutagenesis events occurred after gene sequencing TH genomic DNA related complete 13 coding exons with two-ended partial untranslated regions.
Conclusion: Re-programmed adult mouse fibroblasts-derived dopaminergic neurons were proven to be a safe technology and approach as a potential therapy for neurodegenerative diseases.