hTERT-Immortalized Bone Mesenchymal Stromal Cells Expressing Rat Galanin via a Single Tetracycline-Inducible Lentivirus System

An, Kai Nan; Hui-ping, Liu; Xiao-long, Zhong; Deng, David Y.B.; Zhang, Jingjun; Liu, Zhiheng

doi:10.1155/2017/6082684

Cited by 9 publications

(17 citation statements)

References 37 publications

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“…The hTERT-BMSCs and hTERT-BMSCs//Tet-on/GAL cells have been established, identified, and cryopreserved in our department 18 . For transplantation, cells should be resuscitated and proliferated to near 70% confluence.…”

Section: Methodsmentioning

confidence: 99%

“…Fortunately, these limitations have been overcome via introducing ectopic telomerase catalytic component (human telomerase reverse transcriptase, hTERT) and single inducible tetracycline-controlled gene expression system into BMSCs 16 , 17 . The hTERT–immortalized BMSCs with controllable GAL releases (hTERT-BMSCs/Tet-on/GAL) under the transcriptional control of doxycycline (Dox) have been established and appraised in our previous work 18 . The hTERT-BMSCs/Tet-on/GAL cells are not only easily manipulated, reproducible, and nontumorigenic, but also display high inducibility and controllable release of exogenous GAL in the presence of inducer Dox in vitro .…”

Section: Introductionmentioning

confidence: 99%

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Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in Neuropathic Rats

Cui

Xiao-long

et al. 2022

Cell Transplant

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Management of chronic pain is one of the most difficult problems in modern practice. Grafted human telomerase reverse transcriptase–immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) with inducible galanin (GAL) expression have been considered to be a potentially safe and controllable approach for the alleviation of chronic pain. Therefore, in this study, we aimed to assess the feasibility of hTERT-BMSCs/Tet-on/GAL cells secreting GAL under the transcriptional control of doxycycline (Dox) for controllable pain relief. After transplanted into the subarachnoid space of neuropathic rats induced by spared nerve injury of sciatic nerve, their analgesic actions were investigated by behavioral tests. The results showed that the pain-related behaviors, mechanical allodynia, and thermal hyperalgesia were significantly alleviated during 1 to 7 weeks after grafts of hTERT-BMSCs/Tet-on/GAL cells without motor incoordination. Importantly, these effects could be reversed by GAL receptor antagonist M35 and regulated by Dox induction as compared with control. Moreover, the GAL level in cerebrospinal fluid and spinal GAL receptor 1 (GalR1) expression were correlated with Dox administration, but not GAL receptor 2 (GalR2). Meanwhile, spinal protein kinase Mζ (PKMζ) expression was also inhibited significantly. Taken together, these data suggest that inducible release of GAL from transplanted cells was able to produce controllable pain relief in neuropathic rats via inhibiting the PKMζ activation and activating its GalR1 rather than GalR2. This provides a promising step toward a novel stem cell–based strategy for pain therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in Neuropathic Rats

Cui

Xiao-long

et al. 2022

Cell Transplant

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“…The telomerase activity was measured from fresh hippocampal DG regions using the TRAP EZE ® XL Telomerase Detection Kit (#S7707; Millipore), following the manufacturer’s instruction and previously described (An et al, 2017 ) with some modifications. All samples were analyzed in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Estradiol Replacement at the Critical Period Protects Hippocampal Neural Stem Cells to Improve Cognition in APP/PS1 Mice

Qin

et al. 2020

Front. Aging Neurosci.

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It has been suggested that there is a critical window for estrogen replacement therapy (ERT) in postmenopausal women with Alzheimer's disease (AD); however, supporting evidence is lacking. To address this issue, we investigated the effective period for estradiol (E2) treatment using a mouse model of AD. Four-monthold female APPswe/PSEN1dE9 (APP/PS1) mice were ovariectomized (OVX) and treated with E2 for 2 months starting at the age of 4 months (early period), 6 months (mid-period), or 8 months (late period). We then evaluated hippocampal neurogenesis, β-amyloid (Aβ) accumulation, telomerase activity, and hippocampaldependent behavior. Compared to age-matched wild type mice, APP/PS1 mice with intact ovaries showed increased proliferation of hippocampal neural stem cells (NSCs) at 8 months of age and decreased proliferation of NSCs at 10 months of age; meanwhile, Aβ accumulation progressively increased with age, paralleling the reduced survival of immature neurons. OVX-induced depletion of E2 in APP/PS1 mice resulted in elevated Aβ levels accompanied by elevated p75 neurotrophin receptor (p75 NTR) expression and increased NSC proliferation at 6 months of age, which subsequently declined; accelerated reduction of immature neurons starting from 6 months of age, and reduced telomerase activity and worsened memory performance at 10 months of age. Treatment with E2 in the early period post-OVX, rather than in the mid or late period, abrogated these effects, and p75 NTR inhibition reduced the overproliferation of NSCs in 6-month-old OVX-APP/PS1 mice. Thus, E2 deficiency in young APP/PS1 mice exacerbates cognitive deficits and depletes the hippocampal NSC pool in later life; this can be alleviated by E2 treatment in the early period following OVX, which prevents Aβ/p75 NTR-induced NSC overproliferation and preserves telomerase activity.

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“…Overexpression of hTERT has long been used as a tool to promote cell immortalization 44 . Although there are many successful cases 45 , 46 , 47 , this method is confronted with similar problems to the use of viral oncogenes 10 , 48 .…”

Section: An Overview Of Cr Technologymentioning

confidence: 99%

Conditional reprogramming: next generation cell culture

Wang

et al. 2020

Acta Pharmaceutica Sinica B

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Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

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hTERT-Immortalized Bone Mesenchymal Stromal Cells Expressing Rat Galanin via a Single Tetracycline-Inducible Lentivirus System

Cited by 9 publications

References 37 publications

Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in Neuropathic Rats

Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in Neuropathic Rats

Estradiol Replacement at the Critical Period Protects Hippocampal Neural Stem Cells to Improve Cognition in APP/PS1 Mice

Conditional reprogramming: next generation cell culture

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