Abstract
The use of human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) as vehicles to deliver antinociceptive galanin (GAL) molecules into pain-processing centers represents a novel cell therapy strategy for pain management. Here, an hTERT-BMSCs/Tet-on/GAL cell line was constructed using a single Tet-on-inducible lentivirus system, and subsequent experiments demonstrated that the secretion of rat GAL from hTERT-BMSCs/Tet-on/GAL was switched on and off under the control of an inducer in a dose-dependent manner. The construction of this cell line is the first promising step in the regulation of GAL secretion from hTERT-immortalized BMSCs, and the potential application of this system may provide a stem cell-based research platform for pain.
Highlights
Treatment of chronic neuropathic pain resulting from peripheral nerve injury is one of the most difficult problems in modern clinical practice
These findings suggest that the human telomerase reverse transcriptase (hTERT) gene was integrated into the genomic DNA of rat bone mesenchymal stem cells (BMSCs) and transcribed into mRNA
The immortalized population stably displayed higher telomerase activity (2.4 ± 0.5-fold) compared with their primary counterparts (BMSCs) and the negative control, even after extensive proliferation, whereas much higher activity was observed in the positive control (HeLa cells). These results confirm the functionality of the implemented human telomerase gene in hTERT-BMSCs
Summary
Treatment of chronic neuropathic pain resulting from peripheral nerve injury is one of the most difficult problems in modern clinical practice. Current treatments, such as traditional pharmacological approaches, are often effective for limited periods, these therapies have no practical significance for the progression of pain and can even induce tolerance and unacceptable systemic side effects. Bone marrow stem cells, including the pluripotent hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs), are being considered as potential targets for cell and gene therapy-based approaches against a variety of different diseases. We hypothesized that these newly developed stem cells will serve as efficient and controllable pools for GAL expression within the CNS for further pain study
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