The Experts below are selected from a list of 171 Experts worldwide ranked by ideXlab platform
Jhon Cores - One of the best experts on this subject based on the ideXlab platform.
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A pre-investigational new drug study of lung Spheroid Cell therapy for treating pulmonary fibrosis.
Stem cells translational medicine, 2020Co-Authors: Jhon Cores, Phuong-uyen Dinh, Taylor M. Hensley, Kenneth B. Adler, Leonard J. Lobo, Ke ChengAbstract:Idiopathic pulmonary fibrosis is a lethal interstitial lung disease with unknown etiology, no cure, and few treatment options. Herein, a therapy option is presented that makes use of a heterogeneous population of lung Cells, including progenitor Cells and supporting Cells lines, cultured in adherent and suspension conditions, the latter of which induces spontaneous Spheroid formation. Within these Spheroids, progenitor marker expression is augmented. The Cells, called lung Spheroid Cells, are isolated from fibrotic lungs, expanded, and delivered in single Cell suspensions into rat models of pulmonary fibrosis via tail-vein injections. Two bleomycin-induced fibrotic rat models are used; a syngeneic Wistar-Kyoto rat model, treated with syngeneic Cells, and a xenogeneic nude rat model, treated with human Cells. The first objective was to study the differences in fibrotic progression in the two rat models after bleomycin injury. Nude rat fibrosis formed quickly and extended for 30 days with no self-resolution. Wistar-Kyoto rat fibrosis was more gradual and began to decrease in severity between days 14 and 30. The second goal was to find the minimum effective dose of Cells that demonstrated safe and effective therapeutic value. The resultant minimum effective therapeutic dose, acquired from the nude rat model, was 3 × 106 human Cells. Histological analysis revealed no evidence of tumorigenicity, increased local immunological activity in the lungs, or an increase in liver enzyme production. These data demonstrate the safety and efficacy of lung Spheroid Cells in their application as therapeutic agents for pulmonary fibrosis, as well as their potential for clinical translation.
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inhalation of lung Spheroid Cell secretome and exosomes promotes lung repair in pulmonary fibrosis
Nature Communications, 2020Co-Authors: Phuong-uyen Dinh, Jhon Cores, Taylor M. Hensley, Dipti Paudel, Hayden N Brochu, Kristen D Popowski, Cyndell M Gracieux, Ke Huang, Erin HarrellAbstract:Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide Cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung Spheroid Cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem Cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung Spheroid Cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung Spheroid Cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem Cells.
Phuong-uyen Dinh - One of the best experts on this subject based on the ideXlab platform.
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A pre-investigational new drug study of lung Spheroid Cell therapy for treating pulmonary fibrosis.
Stem cells translational medicine, 2020Co-Authors: Jhon Cores, Phuong-uyen Dinh, Taylor M. Hensley, Kenneth B. Adler, Leonard J. Lobo, Ke ChengAbstract:Idiopathic pulmonary fibrosis is a lethal interstitial lung disease with unknown etiology, no cure, and few treatment options. Herein, a therapy option is presented that makes use of a heterogeneous population of lung Cells, including progenitor Cells and supporting Cells lines, cultured in adherent and suspension conditions, the latter of which induces spontaneous Spheroid formation. Within these Spheroids, progenitor marker expression is augmented. The Cells, called lung Spheroid Cells, are isolated from fibrotic lungs, expanded, and delivered in single Cell suspensions into rat models of pulmonary fibrosis via tail-vein injections. Two bleomycin-induced fibrotic rat models are used; a syngeneic Wistar-Kyoto rat model, treated with syngeneic Cells, and a xenogeneic nude rat model, treated with human Cells. The first objective was to study the differences in fibrotic progression in the two rat models after bleomycin injury. Nude rat fibrosis formed quickly and extended for 30 days with no self-resolution. Wistar-Kyoto rat fibrosis was more gradual and began to decrease in severity between days 14 and 30. The second goal was to find the minimum effective dose of Cells that demonstrated safe and effective therapeutic value. The resultant minimum effective therapeutic dose, acquired from the nude rat model, was 3 × 106 human Cells. Histological analysis revealed no evidence of tumorigenicity, increased local immunological activity in the lungs, or an increase in liver enzyme production. These data demonstrate the safety and efficacy of lung Spheroid Cells in their application as therapeutic agents for pulmonary fibrosis, as well as their potential for clinical translation.
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inhalation of lung Spheroid Cell secretome and exosomes promotes lung repair in pulmonary fibrosis
Nature Communications, 2020Co-Authors: Phuong-uyen Dinh, Jhon Cores, Taylor M. Hensley, Dipti Paudel, Hayden N Brochu, Kristen D Popowski, Cyndell M Gracieux, Ke Huang, Erin HarrellAbstract:Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide Cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung Spheroid Cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem Cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung Spheroid Cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung Spheroid Cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem Cells.
Rüdiger Rudolf - One of the best experts on this subject based on the ideXlab platform.
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Bone Sialoprotein Shows Enhanced Expression in Early, High-Proliferation Stages of Three-Dimensional Spheroid Cell Cultures of Breast Cancer Cell Line MDA-MB-231
Frontiers Media S.A., 2019Co-Authors: Valeh Rustamov, Florian Keller, Julia Klicks, Mathias Hafner, Rüdiger RudolfAbstract:Normally, bone sialoprotein (BSP) is an important contributor to bone micro-calcification. However, it is also highly expressed in bone-metastatic malignancies, including prostate, lung, and breast cancer. In these disorders, BSP correlates with poor prognosis. Its expression in triple-negative breast cancer Cells is enhanced by the transcription factor RUNX2, and both, BSP and RUNX2 are under control of IGF-1 and TGFβ1. Knockdown of BSP or its inactivation by specific antibodies were found to reduce the metastatic potential of MDA-MB-231 triple-negative breast cancer Cells in xenografts. While the role of BSP in bone metastasis was studied using such in vivo models, valid in vitro test systems to investigate BSP biology have been lacking since this protein is expressed at very low levels in classical 2D Cell cultures and the frequently used breast cancer Cell line MDA-MB-231 is difficult to grow in 3D. Here, we have developed a long-term 3D Spheroid culture model using MDA-MB-231 Cells in a sandwich approach using Cell embedding between a non-adherent surface and basement membrane extracts. This allowed consistent growth of Spheroids for more than 21 days. Also, co-culturing of MDA-MB-231 with CCD-1137Sk fibroblasts yielded stably growing Spheroids, suggesting the importance of extraCellular matrix (ECM) in this process. In addition, we have set up a novel and simple open source analysis tool to characterize protein expression in 2D cultures and Spheroids by immunofluorescence. Using this approach in combination with Western blot analysis, the expression profile of BSP was analyzed. BSP was enriched at the rims of Spheroids, both in mono- and co-cultures and its abundance in general correlated with that of TGFβ1 under different conditions, including Spheroid maturation, cytostatic treatment, and fibroblast co-culture. Conversely, correlation of IGF-1 and BSP was limited to mono-culture time course profiles. In conclusion, we present novel tools to study the regulation of gene expression in combination with Cell proliferation and apoptosis in a long-term 3D model of breast cancer and find dynamic abundance profiles of the metastasis-relevant protein BSP and its regulators
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Image_1_Bone Sialoprotein Shows Enhanced Expression in Early, High-Proliferation Stages of Three-Dimensional Spheroid Cell Cultures of Breast Cancer Cell Line MDA-MB-231.TIF
2019Co-Authors: Valeh Rustamov, Florian Keller, Julia Klicks, Mathias Hafner, Rüdiger RudolfAbstract:Normally, bone sialoprotein (BSP) is an important contributor to bone micro-calcification. However, it is also highly expressed in bone-metastatic malignancies, including prostate, lung, and breast cancer. In these disorders, BSP correlates with poor prognosis. Its expression in triple-negative breast cancer Cells is enhanced by the transcription factor RUNX2, and both, BSP and RUNX2 are under control of IGF-1 and TGFβ1. Knockdown of BSP or its inactivation by specific antibodies were found to reduce the metastatic potential of MDA-MB-231 triple-negative breast cancer Cells in xenografts. While the role of BSP in bone metastasis was studied using such in vivo models, valid in vitro test systems to investigate BSP biology have been lacking since this protein is expressed at very low levels in classical 2D Cell cultures and the frequently used breast cancer Cell line MDA-MB-231 is difficult to grow in 3D. Here, we have developed a long-term 3D Spheroid culture model using MDA-MB-231 Cells in a sandwich approach using Cell embedding between a non-adherent surface and basement membrane extracts. This allowed consistent growth of Spheroids for more than 21 days. Also, co-culturing of MDA-MB-231 with CCD-1137Sk fibroblasts yielded stably growing Spheroids, suggesting the importance of extraCellular matrix (ECM) in this process. In addition, we have set up a novel and simple open source analysis tool to characterize protein expression in 2D cultures and Spheroids by immunofluorescence. Using this approach in combination with Western blot analysis, the expression profile of BSP was analyzed. BSP was enriched at the rims of Spheroids, both in mono- and co-cultures and its abundance in general correlated with that of TGFβ1 under different conditions, including Spheroid maturation, cytostatic treatment, and fibroblast co-culture. Conversely, correlation of IGF-1 and BSP was limited to mono-culture time course profiles. In conclusion, we present novel tools to study the regulation of gene expression in combination with Cell proliferation and apoptosis in a long-term 3D model of breast cancer and find dynamic abundance profiles of the metastasis-relevant protein BSP and its regulators.
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Table_1_Bone Sialoprotein Shows Enhanced Expression in Early, High-Proliferation Stages of Three-Dimensional Spheroid Cell Cultures of Breast Cancer Cell Line MDA-MB-231.DOCX
2019Co-Authors: Valeh Rustamov, Florian Keller, Julia Klicks, Mathias Hafner, Rüdiger RudolfAbstract:Normally, bone sialoprotein (BSP) is an important contributor to bone micro-calcification. However, it is also highly expressed in bone-metastatic malignancies, including prostate, lung, and breast cancer. In these disorders, BSP correlates with poor prognosis. Its expression in triple-negative breast cancer Cells is enhanced by the transcription factor RUNX2, and both, BSP and RUNX2 are under control of IGF-1 and TGFβ1. Knockdown of BSP or its inactivation by specific antibodies were found to reduce the metastatic potential of MDA-MB-231 triple-negative breast cancer Cells in xenografts. While the role of BSP in bone metastasis was studied using such in vivo models, valid in vitro test systems to investigate BSP biology have been lacking since this protein is expressed at very low levels in classical 2D Cell cultures and the frequently used breast cancer Cell line MDA-MB-231 is difficult to grow in 3D. Here, we have developed a long-term 3D Spheroid culture model using MDA-MB-231 Cells in a sandwich approach using Cell embedding between a non-adherent surface and basement membrane extracts. This allowed consistent growth of Spheroids for more than 21 days. Also, co-culturing of MDA-MB-231 with CCD-1137Sk fibroblasts yielded stably growing Spheroids, suggesting the importance of extraCellular matrix (ECM) in this process. In addition, we have set up a novel and simple open source analysis tool to characterize protein expression in 2D cultures and Spheroids by immunofluorescence. Using this approach in combination with Western blot analysis, the expression profile of BSP was analyzed. BSP was enriched at the rims of Spheroids, both in mono- and co-cultures and its abundance in general correlated with that of TGFβ1 under different conditions, including Spheroid maturation, cytostatic treatment, and fibroblast co-culture. Conversely, correlation of IGF-1 and BSP was limited to mono-culture time course profiles. In conclusion, we present novel tools to study the regulation of gene expression in combination with Cell proliferation and apoptosis in a long-term 3D model of breast cancer and find dynamic abundance profiles of the metastasis-relevant protein BSP and its regulators.
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Data_Sheet_1_Bone Sialoprotein Shows Enhanced Expression in Early, High-Proliferation Stages of Three-Dimensional Spheroid Cell Cultures of Breast Cancer Cell Line MDA-MB-231.zip
2019Co-Authors: Valeh Rustamov, Florian Keller, Julia Klicks, Mathias Hafner, Rüdiger RudolfAbstract:Normally, bone sialoprotein (BSP) is an important contributor to bone micro-calcification. However, it is also highly expressed in bone-metastatic malignancies, including prostate, lung, and breast cancer. In these disorders, BSP correlates with poor prognosis. Its expression in triple-negative breast cancer Cells is enhanced by the transcription factor RUNX2, and both, BSP and RUNX2 are under control of IGF-1 and TGFβ1. Knockdown of BSP or its inactivation by specific antibodies were found to reduce the metastatic potential of MDA-MB-231 triple-negative breast cancer Cells in xenografts. While the role of BSP in bone metastasis was studied using such in vivo models, valid in vitro test systems to investigate BSP biology have been lacking since this protein is expressed at very low levels in classical 2D Cell cultures and the frequently used breast cancer Cell line MDA-MB-231 is difficult to grow in 3D. Here, we have developed a long-term 3D Spheroid culture model using MDA-MB-231 Cells in a sandwich approach using Cell embedding between a non-adherent surface and basement membrane extracts. This allowed consistent growth of Spheroids for more than 21 days. Also, co-culturing of MDA-MB-231 with CCD-1137Sk fibroblasts yielded stably growing Spheroids, suggesting the importance of extraCellular matrix (ECM) in this process. In addition, we have set up a novel and simple open source analysis tool to characterize protein expression in 2D cultures and Spheroids by immunofluorescence. Using this approach in combination with Western blot analysis, the expression profile of BSP was analyzed. BSP was enriched at the rims of Spheroids, both in mono- and co-cultures and its abundance in general correlated with that of TGFβ1 under different conditions, including Spheroid maturation, cytostatic treatment, and fibroblast co-culture. Conversely, correlation of IGF-1 and BSP was limited to mono-culture time course profiles. In conclusion, we present novel tools to study the regulation of gene expression in combination with Cell proliferation and apoptosis in a long-term 3D model of breast cancer and find dynamic abundance profiles of the metastasis-relevant protein BSP and its regulators.
Taylor M. Hensley - One of the best experts on this subject based on the ideXlab platform.
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A pre-investigational new drug study of lung Spheroid Cell therapy for treating pulmonary fibrosis.
Stem cells translational medicine, 2020Co-Authors: Jhon Cores, Phuong-uyen Dinh, Taylor M. Hensley, Kenneth B. Adler, Leonard J. Lobo, Ke ChengAbstract:Idiopathic pulmonary fibrosis is a lethal interstitial lung disease with unknown etiology, no cure, and few treatment options. Herein, a therapy option is presented that makes use of a heterogeneous population of lung Cells, including progenitor Cells and supporting Cells lines, cultured in adherent and suspension conditions, the latter of which induces spontaneous Spheroid formation. Within these Spheroids, progenitor marker expression is augmented. The Cells, called lung Spheroid Cells, are isolated from fibrotic lungs, expanded, and delivered in single Cell suspensions into rat models of pulmonary fibrosis via tail-vein injections. Two bleomycin-induced fibrotic rat models are used; a syngeneic Wistar-Kyoto rat model, treated with syngeneic Cells, and a xenogeneic nude rat model, treated with human Cells. The first objective was to study the differences in fibrotic progression in the two rat models after bleomycin injury. Nude rat fibrosis formed quickly and extended for 30 days with no self-resolution. Wistar-Kyoto rat fibrosis was more gradual and began to decrease in severity between days 14 and 30. The second goal was to find the minimum effective dose of Cells that demonstrated safe and effective therapeutic value. The resultant minimum effective therapeutic dose, acquired from the nude rat model, was 3 × 106 human Cells. Histological analysis revealed no evidence of tumorigenicity, increased local immunological activity in the lungs, or an increase in liver enzyme production. These data demonstrate the safety and efficacy of lung Spheroid Cells in their application as therapeutic agents for pulmonary fibrosis, as well as their potential for clinical translation.
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inhalation of lung Spheroid Cell secretome and exosomes promotes lung repair in pulmonary fibrosis
Nature Communications, 2020Co-Authors: Phuong-uyen Dinh, Jhon Cores, Taylor M. Hensley, Dipti Paudel, Hayden N Brochu, Kristen D Popowski, Cyndell M Gracieux, Ke Huang, Erin HarrellAbstract:Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide Cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung Spheroid Cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem Cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung Spheroid Cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung Spheroid Cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem Cells.
Erin Harrell - One of the best experts on this subject based on the ideXlab platform.
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inhalation of lung Spheroid Cell secretome and exosomes promotes lung repair in pulmonary fibrosis
Nature Communications, 2020Co-Authors: Phuong-uyen Dinh, Jhon Cores, Taylor M. Hensley, Dipti Paudel, Hayden N Brochu, Kristen D Popowski, Cyndell M Gracieux, Ke Huang, Erin HarrellAbstract:Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide Cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung Spheroid Cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem Cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung Spheroid Cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung Spheroid Cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem Cells.