Slowing Down of the Cell Cycle During Fibroblast Proliferation

Macieira‐Coelho, A.

doi:10.1007/978-3-319-26239-0_3

Cited by 3 publications

(3 citation statements)

References 104 publications

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“…The transient increase in EPO concentration for approximately 10 days stems from the fact that the cellular immune response can develop against viral proteins expressed by the adenovirus (Lippin et al 2005). Besides, terminally differentiated broblasts which were used as cell vehicle has some limitations such as the non-sustained release of the desired secretory protein due to inactivation of vector sequence following transplantation, and also depend on donor's age the expansion capability of normal broblasts may be restricted because they ultimately reach a stage when the cell division cycle slow down leading to cell aging which limits their clinical applications (Macieira-Coelho 2016). In contrast, hWJMSCs used in this study are attractive candidates due to their potential expansion ability, an immuno-privileged status, and easy access for collection, which afford us high-e ciency lentiviral engineering cells, culture, and utilization in vivo of selected modi ed cells (Sironi et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Breast Cancer-related Anemia in Mice Model

Estiri¹,

Estiri²,

Fallah³

et al. 2021

Preprint

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Cancer-related anemia (CRA) negatively influences cancer patients’ survival, disease progression, treatment efficacy, and quality of life. Therefore, development of long-lasting and curative therapies is highly required. In this study, we developed cell and gene therapy strategy for in-vivo delivery of EPO cDNA via genetic engineering human Wharton’s jelly mesenchymal stem cells (hWJMSCs) to long-term produce human EPO protein after transplantation into the mice model of CRA. To evaluate CRA's treatment in cancer-free and cancerous conditions, we designed recombinant breast cancer cell line 4T1 expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) by a lentiviral vector encoding HSV1-TK and injected into mice. After confirming CRA in mice by blood analysis, half of them received ganciclovir for 10 days to clear cancer cells. Meanwhile, we designed another lentiviral vector encoding EPO to transduce hWJMSCs. Following implantation of rhWJMSCs-EPO, the whole peripheral blood samples were collected once per week for 10 weeks. The blood analyzing showed that plasma EPO, hemoglobin (Hb), and hematocrit (Hct) concentration significantly increased and remained at a therapeutic level for >10 weeks in the both treatment groups which indicate that the rhWJMSCs-EPO could improve CRA in both cancer-free and cancerous mice model.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Breast Cancer-related Anemia in Mice Model

Estiri¹,

Estiri²,

Fallah³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…The transient increase in EPO concentration for approximately 10 days stems from the fact that the cellular immune response can develop against viral proteins expressed by the adenovirus [46]. Besides, terminally differentiated broblasts which were used as cell vehicle has some limitations such as the non-sustained release of the desired secretory protein due to inactivation of vector sequence following transplantation, and also, depending on the donor's age the expansion capability of normal broblasts may be restricted because they ultimately reach a stage when the cell division cycle slow down leading to cell aging which limits their clinical applications [47]. In contrast, hWJMSCs used in this study are attractive candidates due to their potential expansion ability, an immuno-privileged status, and easy access for collection, which afford us high-e ciency lentiviral engineering cells, culture, and utilization in vivo of selected modi ed cells[48-50].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Breast Cancer-related Anemia in Mice Model

Estiri¹,

Estiri²,

Fallah³

et al. 2021

Preprint

View full text Add to dashboard Cite

Cancer-related anemia (CRA) negatively influences cancer patients’ survival, disease progression, treatment efficacy, and quality of life (QOL). Current treatments such as iron therapy, red cell transfusion, and erythropoietin-stimulating agents (ESAs) may cause severe adverse effects including hemolytic transfusion reaction and the possibility of host immunity against rhEPO. Therefore, development of long-lasting and curative therapies is highly required. Combined cell and gene therapy platform can introduce a new route for permanent production of erythropoietin (EPO) in the body with various degrees of clinical benefits and avoiding the need for repeat treatments. In this study, we developed cell and gene therapy strategy for in-vivo delivery of EPO cDNA via genetic engineering human Wharton’s jelly mesenchymal stem cells (hWJMSCs) to long-term produce and secret human EPO protein after transplantation into the mice model of CRA. To evaluate CRA's treatment in cancer-free and cancerous conditions, at first, we designed recombinant breast cancer cell line 4T1 expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) by a lentiviral vector encoding HSV1-TK and injected into mice. After 3 weeks, all mice develop metastatic breast cancer associated with acute anemia. Then, we administrated ganciclovir (GCV) for 10 days in half of the mice to clear cancer cells. Meanwhile, we designed another lentiviral vector encoding EPO to transduce hWJMSCs. Following implantation of rhWJMSCs-EPO, the whole peripheral blood samples were collected from the tail vein once per week for 10 weeks which were immediately analyzed for the measurements of EPO, hemoglobin (Hb), and hematocrit (Hct) plasma levels. The blood analysis showed that plasma EPO, hemoglobin (Hb), and hematocrit (Hct) concentration significantly increased and remained at a therapeutic level for >10 weeks in both treatment groups which indicates that the rhWJMSCs-EPO could improve CRA in both cancer-free and cancerous mice model.

show abstract

“…The transient increase in EPO concentration for approximately 10 days stems from the fact that the cellular immune response can develop against viral proteins expressed by the adenovirus (53). Besides, terminally differentiated broblasts which were used as cell vehicle has some limitations such as the non-sustained release of the desired secretory protein due to inactivation of vector sequence following transplantation, and also depend on donor's age the expansion capability of normal broblasts may be restricted because they ultimately reach a stage when the cell division cycle slow down leading to cell aging which limits their clinical applications (54). In contrast, hWJMSCs used in this study are attractive candidates due to their potential expansion ability, an immuno-privileged status, and easy access for collection, which afford us high-e ciency lentiviral engineering cells, culture, and utilization in vivo of selected modi ed cells (55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Cancer-related Anemia in Mice Model

Estiri¹,

Estiri²,

Fallah³

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundCancer-related anemia (CRA) negatively influences cancer patients’ survival, disease progression, treatment efficacy, and quality of life (QOL). Current treatments such as iron therapy, red cell transfusion, and erythropoietin-stimulating agents (ESAs) may cause severe adverse effects. Therefore, development of long-lasting and curative therapies is highly required. Combined cell and gene therapy platform can introduce a new route for permanent production of erythropoietin (EPO) in the body with various degrees of clinical benefits and avoiding the need for repeat treatments.MethodsIn this study, we developed cell and gene therapy strategy for in-vivo delivery of EPO cDNA via genetic engineering human Wharton’s jelly mesenchymal stem cells (hWJMSCs) to long-term produce and secret human EPO protein after transplantation into the mice model of CRA. To evaluate CRA's treatment in cancer-free and cancerous conditions, at first, we designed recombinant breast cancer cell line 4T1 expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) by a lentiviral vector encoding HSV1-TK and injected into mice. After 3 weeks, all mice develop the metastatic breast cancer associated to the acute anemia. Then, we administrated ganciclovir (GCV) for 10 days in half of the mice to clear cancer cells. Meanwhile, we designed another lentiviral vector encoding EPO to transduce hWJMSCs. Following implantation of rhWJMSCs-EPO, the whole peripheral blood samples were collected from the tail vein once per week which were immediately analyzed for the measurements of EPO, hemoglobin (Hb), and hematocrit (Hct) plasma levels. Results We found that after implantation of rhWJMSCs-EPO, plasma EPO, Hb, and Hct concentration significantly increased which rose to a peak in the fourth week and remained at a therapeutic level for >17 weeks in the cancer-free group and >10 weeks in the cancerous group.ConclusionOur data indicate that the EPO-transduced hWJMSCs could improve the anemia of cancer in both cancer-free and cancerous mice model. This significant difference in length of time that Hb and Hct are in therapeutic levels in both treatment groups indicates that developing a precise targeted-therapy to eliminate cancer cells along with an effective treatment for CRA, as we presented here, could bring important clinical benefits.

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Slowing Down of the Cell Cycle During Fibroblast Proliferation

Cited by 3 publications

References 104 publications

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Breast Cancer-related Anemia in Mice Model

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Breast Cancer-related Anemia in Mice Model

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Breast Cancer-related Anemia in Mice Model

Therapeutic Effects of Genetically Modified Wharton’s Jelly Mesenchymal Stem Cells Expressing Erythropoietin on Cancer-related Anemia in Mice Model

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