Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer ... more Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC.
Development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (... more Development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a clinical issue in EGFR mutated non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the potential of combining gefitinib and pemetrexed in preventing the acquisition of EGFR-TKI-resistance in NSCLC cell lines harboring EGFR exon 19 deletion. The effect of different combinatorial schedules of gefitinib and pemetrexed on cell proliferation, cell cycle, apoptosis and acquisition of gefitinib-resistance in PC9 and HCC827 NSCLC cell lines and in PC9 xenograft models was investigated. A simultaneous treatment with gefitinib and pemetrexed enhanced cell growth inhibition and cell death and prevented the appearance of gefitinib-resistance mediated by T790M mutation or epithelial to mesenchymal transition (EMT) in PC9 and HCC827, respectively. In PC9 cells and in PC9 xenografts the combination of gefitinib and pemetrexed, with different schedules, prevented gefitinib-resistance only when pemetrexed was the first treatment, given alone or together with gefitinib. Conversely, when gefitinib alone was firstly administered and pemetrexed sequentially alternated, a negative interaction was observed and no prevention of gefitinib-resistance was documented. The mechanisms of resistance developed in vivo included T790M mutation and EMT. The induction of EMT was a feature of tumors treated with gefitinib when given before pemetrexed, while T790M was recorded only in tumors treated with gefitinib alone. The combination of gefitinib and pemetrexed is effective in preventing gefitinib-resistance; the application of intermittent treatments requires that gefitinib is not administered before pemetrexed.
A prominent role in the pathogenesis of squamous cell carcinoma of the lung (SQCLC) has been attr... more A prominent role in the pathogenesis of squamous cell carcinoma of the lung (SQCLC) has been attributed to the aberrant activation of the phosphoinositide 3-kinase (PI3K) signaling pathway, due to amplification or mutations of the p110α subunit of class I phosphatidylinositol 3-kinase (PIK3CA) gene. The aim of our study was to determine whether different genetic alterations of PIK3CA affect the biological properties of SQCLC and to evaluate the response to specific targeting agents in vitro and in vivo. The effects of NVP-BEZ235, NVP-BKM120 and NVP-BYL719 on 2D/3D cellular growth, epithelial-to-mesenchymal transition and invasiveness were evaluated in E545K or H1047R PIK3CA mutated SQCLC cells and in new-generated clones carrying PIK3CA alterations, as well as in a xenograft model. PIK3CA mutated/amplified cells showed increased growth rate and enhanced migration and invasiveness, associated to an increased activity of RhoA family proteins and to the acquisition of a mesenchymal phe...
Characterization of lymphatic endothelial cells from the respiratory system may be crucial to inv... more Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy.
Interactive CardioVascular and Thoracic Surgery, 2014
The aim of the present study was to characterize the biological properties and in vivo tumourigen... more The aim of the present study was to characterize the biological properties and in vivo tumourigenic potential of mesenchymal stem cells (MSC) obtained from human non-small-cell lung cancers (NSCLC). Methods: Specimens of NSCLC (33 adenocarcinomas, 12 squamous-cell carcinomas) surgically removed from 35 males and 20 females were processed to identify mesenchymal cells from human lung cancer (hLc-MSC). hLc-MSC were separated from neoplastic epithelial cells, frequently growing together with adherent stromal cells, expanded and extensively characterized. Subsequently, female BALB/c nude mice were subcutaneously injected with either 10 6 Calu-3 (human adenocarcinoma cell-line able to reproducibly induce xenografted tumours) alone or in combination with 10 6 hLc-MSCs. Control animals were injected with different doses of hLc-MSCs or Calu-3. Results: Primary cultures of hLc-MSC were obtained from all NSCLC samples. The typical MSC immunophenotype was documented by the expression of CD90, CD105, CD73, CD13, CD44 at FACS analysis. These cells were negative for epithelial antigens, CD45, CD14, CD34. CD117 (c-kit) and CD133 (prominin) were expressed in a limited fraction of cells. Interestingly, the nuclear transcription factors OCT 3/4 and SOX2 involved in stemness, TTF1 (bronchoalveolar), p63 (squamous lineage commitment) were expressed in hLc-MSC isolated from adeno-or squamous-cell carcinomas. In vivo experiments showed that the addition of hLc-MSC to Calu-3 injection was able to increase by 12-fold the dimension of subcutaneous tumours when compared to those induced by Calu-3 alone. Injected cells were detected on sections of xenografted tumours by fluorescence and FISH-analysis of human-specific-sex chromosomes combined with immunohistochemistry: Calu-3-derived cytokeratin-positive adenocarcinoma structures surrounded by hLc-MSC-derived cells were documented. Cytokines and growth-factors network implicated in the cross-talk between tumour cells and hLc-MSC is under intense scrutiny using a transwell system, specific conditioned media and co-cultures. Conclusions: Tumour propagating cells require the inductive interaction with mesenchymal stroma for the in vivo development of lung cancer. Disclosure: No significant relationships.
Cardiovascular & hematological agents in medicinal chemistry, 2010
Cardiovascular diseases and cancer represent respectively the first and second cause of death in ... more Cardiovascular diseases and cancer represent respectively the first and second cause of death in industrialized countries. These two conditions may become synergistic when cardiovascular complications of anti-cancer therapy are considered. More than 70% of childhood and 50% of adult cancer patients can be cured, however this important success obtained by the biological and medical research is obfuscated by emerging findings of early and late morbidity due to cardiovascular events. Although anthracyclines are effective drugs against cancer a dose-dependent cardiotoxic effects whose mechanism has not been elucidated resulting in failure of therapeutic interventions limit their use. Unexpectedly, tyrosine/kinase inhibitors (TKIs) aimed at molecularly interfering with oncogenic pathways, have been implicated in cardiac side effects. Possible explanations of this phenomenon have been ambiguous, further strengthening the need to deepen our understanding on the mechanism of cardiotoxicity....
The adult heart has the capacity to generate new myocytes that is markedly enhanced in acute and ... more The adult heart has the capacity to generate new myocytes that is markedly enhanced in acute and chronic heart failure of ischemic and non-ischemic origin. In addition, a pool of blood trafficking progenitor cells able to sense myocardial damage may home to the sites of injury participating to cardiac repair. This new view of myocardial biology leads to an expanding long-term research and therapeutic goals for cardioprotection. A fundamental concept to be analyzed is whether cardiac diseases are influenced by changes in the properties of tissue specific and circulating progenitors. Loss of self-renewal capacity, impaired growth or increased susceptibility to death may lead to a reduction of progenitors and leave myocardial damage unrepaired. Cardiac progenitors generate all myocardial cell lineages, thus impairment in their growth is expected to be critically involved in the structural and functional modifications of the heart. The fact that, in addition to well known effects of ant...
In humans, there is a documented association between anxiety disorders and cardiovascular disease... more In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease.
Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer ... more Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC.
In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch appli... more In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch application. The rationale was that such matrices would provide conducive environment for the seeded cells at the interphase with PGS. From the microstructural standpoint, PGS was fabricated into dense films and porous PGS scaffolds. From the biological aspect, biomimetic PGS membranes were developed via covalently binding peptides Tyr-Ile-Gly-Ser-Arg (YIGSR) and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), corresponding to the epitope sequences of laminin and fibronectin, respectively onto the surface. To improve and enhance homogenous binding of peptides onto the PGS surface, chemical modification of its surface was carried out. A sequential regime of alkaline hydrolysis with 0.01 M NaOH for 5 min and acidification with 0.01 M HCl for 25 s was optimal. More COOH chemical group was exposed without causing deleterious effect on the bulk properties of the polymer as revealed by the physicochemical analysis carried out. HPLC analysis, chemical imaging and ToF-SIMS were able to establish the successful homogenous functionalization of PGS membranes with the peptides. Finally, the developed biomimetic membranes supported the adhesion and growth of rat and human cardiac progenitor cells.
A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress co... more A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spher-oids. By adopting simple technological solutions and avoiding rotating components, the bio-reactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary in vitro biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection , increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future.
Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer ... more Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC.
Development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (... more Development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a clinical issue in EGFR mutated non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the potential of combining gefitinib and pemetrexed in preventing the acquisition of EGFR-TKI-resistance in NSCLC cell lines harboring EGFR exon 19 deletion. The effect of different combinatorial schedules of gefitinib and pemetrexed on cell proliferation, cell cycle, apoptosis and acquisition of gefitinib-resistance in PC9 and HCC827 NSCLC cell lines and in PC9 xenograft models was investigated. A simultaneous treatment with gefitinib and pemetrexed enhanced cell growth inhibition and cell death and prevented the appearance of gefitinib-resistance mediated by T790M mutation or epithelial to mesenchymal transition (EMT) in PC9 and HCC827, respectively. In PC9 cells and in PC9 xenografts the combination of gefitinib and pemetrexed, with different schedules, prevented gefitinib-resistance only when pemetrexed was the first treatment, given alone or together with gefitinib. Conversely, when gefitinib alone was firstly administered and pemetrexed sequentially alternated, a negative interaction was observed and no prevention of gefitinib-resistance was documented. The mechanisms of resistance developed in vivo included T790M mutation and EMT. The induction of EMT was a feature of tumors treated with gefitinib when given before pemetrexed, while T790M was recorded only in tumors treated with gefitinib alone. The combination of gefitinib and pemetrexed is effective in preventing gefitinib-resistance; the application of intermittent treatments requires that gefitinib is not administered before pemetrexed.
A prominent role in the pathogenesis of squamous cell carcinoma of the lung (SQCLC) has been attr... more A prominent role in the pathogenesis of squamous cell carcinoma of the lung (SQCLC) has been attributed to the aberrant activation of the phosphoinositide 3-kinase (PI3K) signaling pathway, due to amplification or mutations of the p110α subunit of class I phosphatidylinositol 3-kinase (PIK3CA) gene. The aim of our study was to determine whether different genetic alterations of PIK3CA affect the biological properties of SQCLC and to evaluate the response to specific targeting agents in vitro and in vivo. The effects of NVP-BEZ235, NVP-BKM120 and NVP-BYL719 on 2D/3D cellular growth, epithelial-to-mesenchymal transition and invasiveness were evaluated in E545K or H1047R PIK3CA mutated SQCLC cells and in new-generated clones carrying PIK3CA alterations, as well as in a xenograft model. PIK3CA mutated/amplified cells showed increased growth rate and enhanced migration and invasiveness, associated to an increased activity of RhoA family proteins and to the acquisition of a mesenchymal phe...
Characterization of lymphatic endothelial cells from the respiratory system may be crucial to inv... more Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy.
Interactive CardioVascular and Thoracic Surgery, 2014
The aim of the present study was to characterize the biological properties and in vivo tumourigen... more The aim of the present study was to characterize the biological properties and in vivo tumourigenic potential of mesenchymal stem cells (MSC) obtained from human non-small-cell lung cancers (NSCLC). Methods: Specimens of NSCLC (33 adenocarcinomas, 12 squamous-cell carcinomas) surgically removed from 35 males and 20 females were processed to identify mesenchymal cells from human lung cancer (hLc-MSC). hLc-MSC were separated from neoplastic epithelial cells, frequently growing together with adherent stromal cells, expanded and extensively characterized. Subsequently, female BALB/c nude mice were subcutaneously injected with either 10 6 Calu-3 (human adenocarcinoma cell-line able to reproducibly induce xenografted tumours) alone or in combination with 10 6 hLc-MSCs. Control animals were injected with different doses of hLc-MSCs or Calu-3. Results: Primary cultures of hLc-MSC were obtained from all NSCLC samples. The typical MSC immunophenotype was documented by the expression of CD90, CD105, CD73, CD13, CD44 at FACS analysis. These cells were negative for epithelial antigens, CD45, CD14, CD34. CD117 (c-kit) and CD133 (prominin) were expressed in a limited fraction of cells. Interestingly, the nuclear transcription factors OCT 3/4 and SOX2 involved in stemness, TTF1 (bronchoalveolar), p63 (squamous lineage commitment) were expressed in hLc-MSC isolated from adeno-or squamous-cell carcinomas. In vivo experiments showed that the addition of hLc-MSC to Calu-3 injection was able to increase by 12-fold the dimension of subcutaneous tumours when compared to those induced by Calu-3 alone. Injected cells were detected on sections of xenografted tumours by fluorescence and FISH-analysis of human-specific-sex chromosomes combined with immunohistochemistry: Calu-3-derived cytokeratin-positive adenocarcinoma structures surrounded by hLc-MSC-derived cells were documented. Cytokines and growth-factors network implicated in the cross-talk between tumour cells and hLc-MSC is under intense scrutiny using a transwell system, specific conditioned media and co-cultures. Conclusions: Tumour propagating cells require the inductive interaction with mesenchymal stroma for the in vivo development of lung cancer. Disclosure: No significant relationships.
Cardiovascular & hematological agents in medicinal chemistry, 2010
Cardiovascular diseases and cancer represent respectively the first and second cause of death in ... more Cardiovascular diseases and cancer represent respectively the first and second cause of death in industrialized countries. These two conditions may become synergistic when cardiovascular complications of anti-cancer therapy are considered. More than 70% of childhood and 50% of adult cancer patients can be cured, however this important success obtained by the biological and medical research is obfuscated by emerging findings of early and late morbidity due to cardiovascular events. Although anthracyclines are effective drugs against cancer a dose-dependent cardiotoxic effects whose mechanism has not been elucidated resulting in failure of therapeutic interventions limit their use. Unexpectedly, tyrosine/kinase inhibitors (TKIs) aimed at molecularly interfering with oncogenic pathways, have been implicated in cardiac side effects. Possible explanations of this phenomenon have been ambiguous, further strengthening the need to deepen our understanding on the mechanism of cardiotoxicity....
The adult heart has the capacity to generate new myocytes that is markedly enhanced in acute and ... more The adult heart has the capacity to generate new myocytes that is markedly enhanced in acute and chronic heart failure of ischemic and non-ischemic origin. In addition, a pool of blood trafficking progenitor cells able to sense myocardial damage may home to the sites of injury participating to cardiac repair. This new view of myocardial biology leads to an expanding long-term research and therapeutic goals for cardioprotection. A fundamental concept to be analyzed is whether cardiac diseases are influenced by changes in the properties of tissue specific and circulating progenitors. Loss of self-renewal capacity, impaired growth or increased susceptibility to death may lead to a reduction of progenitors and leave myocardial damage unrepaired. Cardiac progenitors generate all myocardial cell lineages, thus impairment in their growth is expected to be critically involved in the structural and functional modifications of the heart. The fact that, in addition to well known effects of ant...
In humans, there is a documented association between anxiety disorders and cardiovascular disease... more In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease.
Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer ... more Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC.
In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch appli... more In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch application. The rationale was that such matrices would provide conducive environment for the seeded cells at the interphase with PGS. From the microstructural standpoint, PGS was fabricated into dense films and porous PGS scaffolds. From the biological aspect, biomimetic PGS membranes were developed via covalently binding peptides Tyr-Ile-Gly-Ser-Arg (YIGSR) and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), corresponding to the epitope sequences of laminin and fibronectin, respectively onto the surface. To improve and enhance homogenous binding of peptides onto the PGS surface, chemical modification of its surface was carried out. A sequential regime of alkaline hydrolysis with 0.01 M NaOH for 5 min and acidification with 0.01 M HCl for 25 s was optimal. More COOH chemical group was exposed without causing deleterious effect on the bulk properties of the polymer as revealed by the physicochemical analysis carried out. HPLC analysis, chemical imaging and ToF-SIMS were able to establish the successful homogenous functionalization of PGS membranes with the peptides. Finally, the developed biomimetic membranes supported the adhesion and growth of rat and human cardiac progenitor cells.
A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress co... more A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spher-oids. By adopting simple technological solutions and avoiding rotating components, the bio-reactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary in vitro biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection , increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future.
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Papers by Denise Madeddu