Stem cell-based therapeutic strategy in delaying prion disease

2021 ◽  
pp. 271-280
Author(s):  
Sanjay Kisan Metkar ◽  
Koyeli Girigoswami ◽  
Agnishwar Girigoswami
Keyword(s):  
Stem Cell ◽  
Prion Disease ◽  
Therapeutic Strategy

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

2020 ◽  
Vol 20 (17) ◽  
pp. 2074-2081
Author(s):  
Onur Tokgun ◽  
Pervin E. Tokgun ◽  
Kubilay Inci ◽  
Hakan Akca
Keyword(s):  
Lung Cancer ◽  
Stem Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Strategy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Shrna Vector

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

scholarly journals Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Prakash Chinnaiyan ◽  
Alexander ARA Anderson ◽  
Anita Hjelmeland ◽  
David Basanta
Keyword(s):  
Stem Cell ◽  
Therapeutic Strategy ◽  
Tissue Growth ◽  
Genetic Mutations ◽  
Phenotypic Traits ◽  
Cell Behaviour ◽  
New Information ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Direct Feedback

Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non- specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

scholarly journals Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2746
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cell ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Therapeutic Strategy ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Effective Therapeutic Strategy ◽  
Cancer Types ◽  
The Brain

The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.

Stem cell transplantation as a therapeutic strategy for traumatic brain injury

2005 ◽  
Vol 15 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Luca Longhi ◽  
Elisa R. Zanier ◽  
Nicolas Royo ◽  
Nino Stocchetti ◽  
Tracy K. McIntosh
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cell ◽  
Brain Injury ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Strategy

scholarly journals Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Prakash Chinnaiyan ◽  
Alexander ARA Anderson ◽  
Anita Hjelmeland ◽  
David Basanta
Keyword(s):  
Stem Cell ◽  
Therapeutic Strategy ◽  
Tissue Growth ◽  
Genetic Mutations ◽  
Phenotypic Traits ◽  
Cell Behaviour ◽  
New Information ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Direct Feedback

Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non- specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

scholarly journals Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shobha Regmi ◽  
Shiva Pathak ◽  
Tung Pham Thanh ◽  
Tiep Tien Nguyen ◽  
Jong-Hyuk Sung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Therapeutic Strategy ◽  
Hanging Drop ◽  
Immunomodulatory Effects ◽  
Promising Alternative ◽  
Hanging Drop Method ◽  
Transplantation Outcomes ◽  
3D Spheroids

Abstract Background Systemic inflammatory response syndrome (SIRS) is common in severe fulminant hepatic failure (FHF) and has a high mortality rate (20–50%) due to irreversible cerebral edema or sepsis. Stem cell-based treatment has emerged as a promising alternative therapeutic strategy to prolong the survival of patients suffering from FHF via the inhibition of SIRS due to their immunomodulatory effects. Methods 3D spheroids of adipose-derived mesenchymal stem cells (3D-ADSC) were prepared by the hanging drop method. The efficacy of the 3D-ADSC to rescue FHF was evaluated in a d-galactosamine/lipopolysaccharide (GalN/LPS)-induced mouse model of FHF via intraportal transplantation of the spheroids. Results Intraportally delivered 3D-ADSC better engrafted and localized into the damaged livers compared to 2D-cultured adipose-derived mesenchymal stem cells (2D-ADSC). Transplantation of 3D-ADSC rescued 50% of mice from FHF-induced lethality, whereas only 20% of mice survived when 2D-ADSC were transplanted. The improved transplantation outcomes correlated with the enhanced immunomodulatory effect of 3D-ADSC in the liver microenvironment. Conclusion The study shows that the transplantation of optimized 3D-ADSC can efficiently ameliorate GalN/LPS-induced FHF due to improved viability, resistance to exogenous ROS, and enhanced immunomodulatory effects of 3D-ADSC.

Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell–derived exosomes

2021 ◽  
pp. 1-10
Author(s):  
Motoshi Kozakai ◽  
Yuji Narita ◽  
Aika Yamawaki-Ogata ◽  
Kazuro L Fujimoto ◽  
Masato Mutsuga ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Therapeutic Strategy ◽  
Aortic Aneurysms
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