author_facet Chulpanova, Daria S.
Solovyeva, Valeriya V.
James, Victoria
Arkhipova, Svetlana S.
Gomzikova, Marina O.
Garanina, Ekaterina E.
Akhmetzyanova, Elvira R.
Tazetdinova, Leysan G.
Khaiboullina, Svetlana F.
Rizvanov, Albert A.
Chulpanova, Daria S.
Solovyeva, Valeriya V.
James, Victoria
Arkhipova, Svetlana S.
Gomzikova, Marina O.
Garanina, Ekaterina E.
Akhmetzyanova, Elvira R.
Tazetdinova, Leysan G.
Khaiboullina, Svetlana F.
Rizvanov, Albert A.
author Chulpanova, Daria S.
Solovyeva, Valeriya V.
James, Victoria
Arkhipova, Svetlana S.
Gomzikova, Marina O.
Garanina, Ekaterina E.
Akhmetzyanova, Elvira R.
Tazetdinova, Leysan G.
Khaiboullina, Svetlana F.
Rizvanov, Albert A.
spellingShingle Chulpanova, Daria S.
Solovyeva, Valeriya V.
James, Victoria
Arkhipova, Svetlana S.
Gomzikova, Marina O.
Garanina, Ekaterina E.
Akhmetzyanova, Elvira R.
Tazetdinova, Leysan G.
Khaiboullina, Svetlana F.
Rizvanov, Albert A.
Bioengineering
Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
Bioengineering
author_sort chulpanova, daria s.
spelling Chulpanova, Daria S. Solovyeva, Valeriya V. James, Victoria Arkhipova, Svetlana S. Gomzikova, Marina O. Garanina, Ekaterina E. Akhmetzyanova, Elvira R. Tazetdinova, Leysan G. Khaiboullina, Svetlana F. Rizvanov, Albert A. 2306-5354 MDPI AG Bioengineering http://dx.doi.org/10.3390/bioengineering7020059 <jats:p>High-dose recombinant interleukin 2 (IL2) therapy has been shown to be successful in renal cell carcinoma and metastatic melanoma. However, systemic administration of high doses of IL2 can be toxic, causing capillary leakage syndrome and stimulating pro-tumor immune response. One of the strategies to reduce the systemic toxicity of IL2 is the use of mesenchymal stem cells (MSCs) as a vehicle for the targeted delivery of IL2. Human adipose tissue-derived MSCs were transduced with lentivirus encoding IL2 (hADSCs-IL2) or blue fluorescent protein (BFP) (hADSCs-BFP). The proliferation, immunophenotype, cytokine profile and ultrastructure of hADSCs-IL2 and hADSCs-BFP were determined. The effect of hADSCs on activation of peripheral blood mononuclear cells (PBMCs) and proliferation and viability of SH-SY5Y neuroblastoma cells after co-culture with native hADSCs, hADSCs-BFP or hADSCs-IL2 on plastic and Matrigel was evaluated. Ultrastructure and cytokine production by hADSCs-IL2 showed modest changes in comparison with hADSCs and hADSCs-BFP. Conditioned medium from hADSC-IL2 affected tumor cell proliferation, increasing the proliferation of SH-SY5Y cells and also increasing the number of late-activated T-cells, natural killer (NK) cells, NKT-cells and activated T-killers. Conversely, hADSC-IL2 co-culture led to a decrease in SH-SY5Y proliferation on plastic and Matrigel. These data show that hADSCs-IL2 can reduce SH-SY5Y proliferation and activate PBMCs in vitro. However, IL2-mediated therapeutic effects of hADSCs could be offset by the increased expression of pro-oncogenes, as well as the natural ability of hADSCs to promote the progression of some tumors.</jats:p> Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro Bioengineering
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title Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_unstemmed Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_full Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_fullStr Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_full_unstemmed Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_short Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_sort human mesenchymal stem cells overexpressing interleukin 2 can suppress proliferation of neuroblastoma cells in co-culture and activate mononuclear cells in vitro
topic Bioengineering
url http://dx.doi.org/10.3390/bioengineering7020059
publishDate 2020
physical 59
description <jats:p>High-dose recombinant interleukin 2 (IL2) therapy has been shown to be successful in renal cell carcinoma and metastatic melanoma. However, systemic administration of high doses of IL2 can be toxic, causing capillary leakage syndrome and stimulating pro-tumor immune response. One of the strategies to reduce the systemic toxicity of IL2 is the use of mesenchymal stem cells (MSCs) as a vehicle for the targeted delivery of IL2. Human adipose tissue-derived MSCs were transduced with lentivirus encoding IL2 (hADSCs-IL2) or blue fluorescent protein (BFP) (hADSCs-BFP). The proliferation, immunophenotype, cytokine profile and ultrastructure of hADSCs-IL2 and hADSCs-BFP were determined. The effect of hADSCs on activation of peripheral blood mononuclear cells (PBMCs) and proliferation and viability of SH-SY5Y neuroblastoma cells after co-culture with native hADSCs, hADSCs-BFP or hADSCs-IL2 on plastic and Matrigel was evaluated. Ultrastructure and cytokine production by hADSCs-IL2 showed modest changes in comparison with hADSCs and hADSCs-BFP. Conditioned medium from hADSC-IL2 affected tumor cell proliferation, increasing the proliferation of SH-SY5Y cells and also increasing the number of late-activated T-cells, natural killer (NK) cells, NKT-cells and activated T-killers. Conversely, hADSC-IL2 co-culture led to a decrease in SH-SY5Y proliferation on plastic and Matrigel. These data show that hADSCs-IL2 can reduce SH-SY5Y proliferation and activate PBMCs in vitro. However, IL2-mediated therapeutic effects of hADSCs could be offset by the increased expression of pro-oncogenes, as well as the natural ability of hADSCs to promote the progression of some tumors.</jats:p>
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author Chulpanova, Daria S., Solovyeva, Valeriya V., James, Victoria, Arkhipova, Svetlana S., Gomzikova, Marina O., Garanina, Ekaterina E., Akhmetzyanova, Elvira R., Tazetdinova, Leysan G., Khaiboullina, Svetlana F., Rizvanov, Albert A.
author_facet Chulpanova, Daria S., Solovyeva, Valeriya V., James, Victoria, Arkhipova, Svetlana S., Gomzikova, Marina O., Garanina, Ekaterina E., Akhmetzyanova, Elvira R., Tazetdinova, Leysan G., Khaiboullina, Svetlana F., Rizvanov, Albert A., Chulpanova, Daria S., Solovyeva, Valeriya V., James, Victoria, Arkhipova, Svetlana S., Gomzikova, Marina O., Garanina, Ekaterina E., Akhmetzyanova, Elvira R., Tazetdinova, Leysan G., Khaiboullina, Svetlana F., Rizvanov, Albert A.
author_sort chulpanova, daria s.
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description <jats:p>High-dose recombinant interleukin 2 (IL2) therapy has been shown to be successful in renal cell carcinoma and metastatic melanoma. However, systemic administration of high doses of IL2 can be toxic, causing capillary leakage syndrome and stimulating pro-tumor immune response. One of the strategies to reduce the systemic toxicity of IL2 is the use of mesenchymal stem cells (MSCs) as a vehicle for the targeted delivery of IL2. Human adipose tissue-derived MSCs were transduced with lentivirus encoding IL2 (hADSCs-IL2) or blue fluorescent protein (BFP) (hADSCs-BFP). The proliferation, immunophenotype, cytokine profile and ultrastructure of hADSCs-IL2 and hADSCs-BFP were determined. The effect of hADSCs on activation of peripheral blood mononuclear cells (PBMCs) and proliferation and viability of SH-SY5Y neuroblastoma cells after co-culture with native hADSCs, hADSCs-BFP or hADSCs-IL2 on plastic and Matrigel was evaluated. Ultrastructure and cytokine production by hADSCs-IL2 showed modest changes in comparison with hADSCs and hADSCs-BFP. Conditioned medium from hADSC-IL2 affected tumor cell proliferation, increasing the proliferation of SH-SY5Y cells and also increasing the number of late-activated T-cells, natural killer (NK) cells, NKT-cells and activated T-killers. Conversely, hADSC-IL2 co-culture led to a decrease in SH-SY5Y proliferation on plastic and Matrigel. These data show that hADSCs-IL2 can reduce SH-SY5Y proliferation and activate PBMCs in vitro. However, IL2-mediated therapeutic effects of hADSCs could be offset by the increased expression of pro-oncogenes, as well as the natural ability of hADSCs to promote the progression of some tumors.</jats:p>
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spelling Chulpanova, Daria S. Solovyeva, Valeriya V. James, Victoria Arkhipova, Svetlana S. Gomzikova, Marina O. Garanina, Ekaterina E. Akhmetzyanova, Elvira R. Tazetdinova, Leysan G. Khaiboullina, Svetlana F. Rizvanov, Albert A. 2306-5354 MDPI AG Bioengineering http://dx.doi.org/10.3390/bioengineering7020059 <jats:p>High-dose recombinant interleukin 2 (IL2) therapy has been shown to be successful in renal cell carcinoma and metastatic melanoma. However, systemic administration of high doses of IL2 can be toxic, causing capillary leakage syndrome and stimulating pro-tumor immune response. One of the strategies to reduce the systemic toxicity of IL2 is the use of mesenchymal stem cells (MSCs) as a vehicle for the targeted delivery of IL2. Human adipose tissue-derived MSCs were transduced with lentivirus encoding IL2 (hADSCs-IL2) or blue fluorescent protein (BFP) (hADSCs-BFP). The proliferation, immunophenotype, cytokine profile and ultrastructure of hADSCs-IL2 and hADSCs-BFP were determined. The effect of hADSCs on activation of peripheral blood mononuclear cells (PBMCs) and proliferation and viability of SH-SY5Y neuroblastoma cells after co-culture with native hADSCs, hADSCs-BFP or hADSCs-IL2 on plastic and Matrigel was evaluated. Ultrastructure and cytokine production by hADSCs-IL2 showed modest changes in comparison with hADSCs and hADSCs-BFP. Conditioned medium from hADSC-IL2 affected tumor cell proliferation, increasing the proliferation of SH-SY5Y cells and also increasing the number of late-activated T-cells, natural killer (NK) cells, NKT-cells and activated T-killers. Conversely, hADSC-IL2 co-culture led to a decrease in SH-SY5Y proliferation on plastic and Matrigel. These data show that hADSCs-IL2 can reduce SH-SY5Y proliferation and activate PBMCs in vitro. However, IL2-mediated therapeutic effects of hADSCs could be offset by the increased expression of pro-oncogenes, as well as the natural ability of hADSCs to promote the progression of some tumors.</jats:p> Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro Bioengineering
spellingShingle Chulpanova, Daria S., Solovyeva, Valeriya V., James, Victoria, Arkhipova, Svetlana S., Gomzikova, Marina O., Garanina, Ekaterina E., Akhmetzyanova, Elvira R., Tazetdinova, Leysan G., Khaiboullina, Svetlana F., Rizvanov, Albert A., Bioengineering, Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro, Bioengineering
title Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_full Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_fullStr Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_full_unstemmed Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_short Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
title_sort human mesenchymal stem cells overexpressing interleukin 2 can suppress proliferation of neuroblastoma cells in co-culture and activate mononuclear cells in vitro
title_unstemmed Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro
topic Bioengineering
url http://dx.doi.org/10.3390/bioengineering7020059