Cellular and molecular bioengineering最新文献

{"title":"Pioglitazone Antagonized the Effects of Advanced Glycation End Products on Achilles Tendon Healing and Improved the Recovery of Tendon Biomechanical Properties","authors":"Gengxin Jia, Xiaoyang Jia, Juan Yang, Tianhao Shi, Minfei Qiang, Yanxi Chen","doi":"10.1007/s12195-024-00800-7","DOIUrl":"https://doi.org/10.1007/s12195-024-00800-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Advanced glycation end products (AGEs) often accumulate in the Achilles tendon during the course of diabetes. This study aims to determine the impact of AGEs on tendon repair and explore the role of pioglitazone in mitigating this impact.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Forty-eight male 8 week-old Sprague Dawley rats were selected in this study. After transection of Achilles tendon, the rats were randomly divided into four groups. The Achilles tendons of rats were injected with 1000 mmol/L D-ribose to elevate the content of AGEs within the tendons in two groups, the remaining two groups received injections of phosphate buffered saline (PBS) solution. Subsequently, the first two groups were respectively received oral administration of pioglitazone (20 mg/kg/day) and PBS. The remaining two groups were given the same treatment. The expression of the collagen-I, TNF-α, IL-6 of the repaired tendon were detected. The macroscopic, pathologic and biomechanical aspects of tendon healing were also evaluated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>AGEs accumulation in tendon during the healing process increases the expression of inflammatory factors such as TNF-α and IL-6, leading to insufficient synthesis of collagen-I and delayed recovery of the tendon's tensile strength. Pioglitazone significantly attenuated the damage caused by AGEs to the tendon healing process, effectively improving the recovery of tendon tensile strength. Pioglitazone could not inhibit the generation of AGEs in the tissue and also had no impact on the normal healing process of the tendon.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Pioglitazone could prevent the deleterious impact of AGEs on the Achilles tendon healing and improve the biomechanical properties of the tendon.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"159 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioblastoma Cells Use an Integrin- and CD44-Mediated Motor-Clutch Mode of Migration in Brain Tissue","authors":"Sarah M. Anderson, Marcus Kelly, David J. Odde","doi":"10.1007/s12195-024-00799-x","DOIUrl":"https://doi.org/10.1007/s12195-024-00799-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Glioblastoma (GBM) is an aggressive malignant brain tumor with 2 year survival rates of 6.7% (Stupp et al. in J Clin Oncol Off J Am Soc Clin Oncol 25:4127–4136, 2007; Mohammed et al. in Rep Pract Oncol Radiother 27:1026–1036, 2002). One key characteristic of the disease is the ability of glioblastoma cells to migrate rapidly and spread throughout healthy brain tissue (Lefranc et al. in J Clin Oncol Off J Am Soc Clin Oncol 23:2411–2422, 2005; Hoelzinger et al. in J Natl Cancer Inst 21:1583–1593, 2007). To develop treatments that effectively target cell migration, it is important to understand the fundamental mechanism driving cell migration in brain tissue. Several models of cell migration have been proposed, including the motor-clutch, bleb-based motility, and osmotic engine models.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Here we utilized confocal imaging to measure traction dynamics and migration speeds of glioblastoma cells in mouse organotypic brain slices to identify the mode of cell migration.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We found that nearly all cell-vasculature interactions reflected pulling, rather than pushing, on vasculature at the cell leading edge, a finding consistent with a motor-clutch mode of migration, and inconsistent with an osmotic engine model or confined bleb-based migration. Reducing myosin motor activity, a key component in the motor-clutch model, was found to decrease migration speed at high doses for all cell types including U251 and 6 low-passage patient-derived xenograft lines (3 proneural and 3 mesenchymal subtypes). Variable responses were found at low doses, consistent with a motor-clutch mode of migration which predicts a biphasic relationship between migration speed and motor-to-clutch ratio. Targeting of molecular clutches including integrins and CD44 slowed migration of U251 cells.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Overall we find that glioblastoma cell migration is most consistent with a motor-clutch mechanism to migrate through brain tissue ex vivo, and that both integrins and CD44, as well as myosin motors, play an important role in constituting the adhesive clutch.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"30 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140032501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Tumor Models to Study Cancer Stemness-Mediated Drug Resistance","authors":"Astha Lamichhane, Hossein Tavana","doi":"10.1007/s12195-024-00798-y","DOIUrl":"https://doi.org/10.1007/s12195-024-00798-y","url":null,"abstract":"<p>Solid tumors often contain genetically different populations of cancer cells, stromal cells, various structural and soluble proteins, and other soluble signaling molecules. The American Cancer society estimated 1,958,310 new cancer cases and 609,820 cancer deaths in the United States in 2023. A major barrier against successful treatment of cancer patients is drug resistance. Gain of stem cell-like states by cancer cells under drug pressure or due to interactions with the tumor microenvironment is a major mechanism that renders therapies ineffective. Identifying approaches to target cancer stem cells is expected to improve treatment outcomes for patients. Most of our understanding of drug resistance and the role of cancer stemness is from monolayer cell cultures. Recent advances in cell culture technologies have enabled developing sophisticated three-dimensional tumor models that facilitate mechanistic studies of cancer drug resistance. This review summarizes the role of cancer stemness in drug resistance and highlights the various tumor models that are used to discover the underlying mechanisms and test potentially novel therapeutics.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"138 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139917453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological Features of Colorectal Adenocarcinoma Patients Related to MLH1","authors":"","doi":"10.1007/s12195-024-00797-z","DOIUrl":"https://doi.org/10.1007/s12195-024-00797-z","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p>MLH1, one of the MMR proteins, is linked to DNA replication, its role being to repair the incorrect DNA sequences and to replace them with proper ones. The loss of the MLH1 gene expression is part of Lynch syndrome which can lead to a series of cancers like colorectal and endometrial ones. The aim of this paper is to correlate the levels of MLH1 in four different bio-logical fluids with clinicopathological features in colorectal cancer patients in order to predict them with high probability. Therefore, a mathematical model with given code in Matlab has been proposed to get the clinicopathological features with high probability by only introducing the values for MLH1 concentrations. All these data can be obtained in a very short time even before surgery which can be very helpful the surgeon and the oncologist.</p> </span> <span> <h3>Methods</h3> <p>Four types of samples (whole blood, saliva, urine and tissue) were analyzed using stochastic microsensors; concentrations of MLH1 were determined and compared with different macroscopic and micro-scopic pathological features to obtain mathematical models for early, non-invasive diagnostic of colorectal adenocarcinoma.</p> </span> <span> <h3>Results</h3> <p>There have been established criteria and mathematical models for tumor location, TNM grading system, depth of the tumor, lymphatic, vascular and perineural invasions and the presence of mucus in the tumoral mass.</p> </span> <span> <h3>Conclusions</h3> <p>By using whole blood, saliva and urine samples, the location can be approximated. The proposed mathematical models aimed to allow a minim/noninvasive characterization of the tumor and its location which can help the surgeon and the oncologist to choose faster the personalized treatment.</p> </span>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"89 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139917456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Model for Chemomechanical Coupling of Kinesin-3 Motor","authors":"Ping Xie","doi":"10.1007/s12195-024-00795-1","DOIUrl":"https://doi.org/10.1007/s12195-024-00795-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Kinesin-3 motor, which is in the monomeric and inactive form in solution, after cargo-induced dimerization can step on microtubules towards the plus end with a high velocity and a supperprocessivity, which is responsible for transporting the cargo in axons and dendrites. The kinesin-3 motor has a large initial landing rate to microtubules and spends the majority of its stepping cycle in a one-head-bound state. Under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To understand the physical origin of the peculiar features for the kinesin-3 motor, a model is presented here for its chemomechanical coupling. Based on the model the dynamics of the motor under no load, under the ramping load and under the constant load is studied analytically.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The theoretical results explain well the available experimental data under no load and under the ramping load. For comparison, the corresponding available experimental data for the kinesin-1 motor under the ramping load are also explained. The predicted results of the velocity, dissociation rate and run length versus the constant load for the kinesin-3 motor are provided.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The study has strong implications for the chemomechanical coupling mechanism of the kinesin-3 dimer. The origin of the kinesin-3 dimer in the predominant one-head-bound state is due to the fact that the rate of ATP transition to ADP in the trailing head is much larger than that of ADP release from the MT-bound head. The study shows that the kinesin-3 ADP-head has an evidently longer interaction distance with microtubule than the kinesin-1 ADP-head, explaining why in the initial ADP state the kinesin-3 motor has the much larger landing rate than the kinesin-1 motor and why under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"133 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139902865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Hematocrit Level and Integrin αIIbβIII Function on vWF-Mediated Platelet Adhesion and Shear-Induced Platelet Aggregation in a Sudden Expansion","authors":"","doi":"10.1007/s12195-024-00796-0","DOIUrl":"https://doi.org/10.1007/s12195-024-00796-0","url":null,"abstract":"&lt;h3&gt;Abstract&lt;/h3&gt; &lt;span&gt; &lt;h3&gt;Purpose&lt;/h3&gt; &lt;p&gt;Shear-mediated thrombosis is a clinically relevant phenomenon that underlies excessive arterial thrombosis and device-induced thrombosis. Red blood cells are known to mechanically contribute to physiological hemostasis through margination of platelets and vWF, facilitating the unfurling of vWF multimers, and increasing the fraction of thrombus-contacting platelets. Shear also plays a role in this phenomenon, increasing both the degree of margination and the near-wall forces experienced by vWF and platelets leading to unfurling and activation. Despite this, the contribution of red blood cells in shear-induced platelet aggregation has not been fully investigated—specifically the effect of elevated hematocrit has not yet been demonstrated.&lt;/p&gt; &lt;/span&gt; &lt;span&gt; &lt;h3&gt;Methods&lt;/h3&gt; &lt;p&gt;Here, a microfluidic model of a sudden expansion is presented as a platform for investigating platelet adhesion at hematocrits ranging from 0 to 60% and shear rates ranging from 1000 to 10,000 s&lt;sup&gt;−1&lt;/sup&gt;. The sudden expansion geometry models nonphysiological flow separation characteristic to mechanical circulatory support devices, and the validatory framework of the FDA benchmark nozzle. PDMS microchannels were fabricated and coated with human collagen. Platelets were fluorescently tagged, and blood was reconstituted at variable hematocrit prior to perfusion experiments. Integrin function of selected blood samples was inhibited by a blocking antibody, and platelet adhesion and aggregation over the course of perfusion was monitored.&lt;/p&gt; &lt;/span&gt; &lt;span&gt; &lt;h3&gt;Results&lt;/h3&gt; &lt;p&gt;Increasing shear rates at physiological and elevated hematocrit levels facilitate robust platelet adhesion and formation of large aggregates. Shear-induced platelet aggregation is demonstrated to be dependent on both α&lt;sub&gt;IIb&lt;/sub&gt;β&lt;sub&gt;III&lt;/sub&gt; function and the presence of red blood cells. Inhibition of α&lt;sub&gt;IIb&lt;/sub&gt;β&lt;sub&gt;III&lt;/sub&gt; results in an 86.4% reduction in overall platelet adhesion and an 85.7% reduction in thrombus size at 20-60% hematocrit. Hematocrit levels of 20% are inadequate for effective platelet margination and subsequent vWF tethering, resulting in notable decreases in platelet adhesion at 5000 and 10,000 s&lt;sup&gt;-1&lt;/sup&gt; compared to 40% and 60%. Inhibition of α&lt;sub&gt;IIb&lt;/sub&gt;β&lt;sub&gt;III&lt;/sub&gt; triggered dramatic reductions in overall thrombus coverage and large aggregate formation. Stability of platelets tethered by vWF are demonstrated to be α&lt;sub&gt;IIb&lt;/sub&gt;β&lt;sub&gt;III&lt;/sub&gt;-dependent, as adhesion of single platelets treated with A2A9, an anti-α&lt;sub&gt;IIb&lt;/sub&gt;β&lt;sub&gt;III&lt;/sub&gt; blocking antibody, is transient and did not lead to sustained thrombus formation.&lt;/p&gt; &lt;/span&gt; &lt;span&gt; &lt;h3&gt;Conclusions&lt;/h3&gt; &lt;p&gt;This study highlights driving factors in vWF-mediated platelet adhesion that are relevant to clinical suppression of shear-induced thrombosis and in vitro assays of platelet adhesion. Primarily, increasing hematocrit promotes platelet margination, permit","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"156 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurogenic Cell Behavior in 3D Culture Enhanced Within a Highly Compliant Synthetic Hydrogel Platform Formed via Competitive Crosslinking","authors":"","doi":"10.1007/s12195-024-00794-2","DOIUrl":"https://doi.org/10.1007/s12195-024-00794-2","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Purpose</h3> <p>Scaffold materials that better support neurogenesis are still needed to improve cell therapy outcomes for neural tissue damage. We have used a modularly tunable, highly compliant, degradable hydrogel to explore the impacts of hydrogel compliance stiffness on neural differentiation. Here we implemented competitive matrix crosslinking mechanics to finely tune synthetic hydrogel moduli within soft tissue stiffnesses, a range much softer than typically achievable in synthetic crosslinked hydrogels, providing a modularly controlled and ultrasoft 3D culture model which supports and enhances neurogenic cell behavior.</p> </span> <span> <h3>Methods</h3> <p>Soluble competitive allyl monomers were mixed with proteolytically-degradable poly(ethylene glycol) diacrylate derivatives and crosslinked to form a matrix, and resultant hydrogel stiffness and diffusive properties were evaluated. Neural PC12 cells or primary rat fetal neural stem cells (NSCs) were encapsulated within the hydrogels, and cell morphology and phenotype were investigated to understand cell-matrix interactions and the effects of environmental stiffness on neural cell behavior within this model.</p> </span> <span> <h3>Results</h3> <p>Addition of allyl monomers caused a concentration-dependent decrease in hydrogel compressive modulus from 4.40 kPa to 0.26 kPa (natural neural tissue stiffness) without influencing soluble protein diffusion kinetics through the gel matrix. PC12 cells encapsulated in the softest hydrogels showed significantly enhanced neurite extension in comparison to PC12s in all other hydrogel stiffnesses tested. Encapsulated neural stem cells demonstrated significantly greater spreading and elongation in 0.26 kPa alloc hydrogels than in 4.4 kPa hydrogels. When soluble growth factor deprivation (for promotion of neural differentiation) was evaluated within the neural stiffness gels (0.26 kPa), NSCs showed increased neuronal marker expression, indicating early enhancement of neurogenic differentiation.</p> </span> <span> <h3>Conclusions</h3> <p>Implementing allyl-acrylate crosslinking competition reduced synthetic hydrogel stiffness to provide a supportive environment for 3D neural tissue culture, resulting in enhanced neurogenic behavior of encapsulated cells. These results indicate the potential suitability of this ultrasoft hydrogel system as a model platform for further investigating environmental factors on neural cell behavior.</p> </span>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"313 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporation of ChatGPT and Other Large Language Models into a Graduate Level Computational Bioengineering Course","authors":"Michael R. King, Adam M. Abdulrahman, Mark I. Petrovic, Patricia L. Poley, Sarah P. Hall, Surat Kulapatana, Zachary E. Lamantia","doi":"10.1007/s12195-024-00793-3","DOIUrl":"https://doi.org/10.1007/s12195-024-00793-3","url":null,"abstract":"<p>The remarkable capabilities of generative artificial intelligence and large language models (LLMs) such as ChatGPT have delighted users around the world. Educators have regarded these tools as either a cause for great concern, an opportunity to educate students on cutting-edge technology, or often some combination of the two. Throughout the Fall 2023 semester, we explored the use of ChatGPT (and Bard, among other LLMs) in a graduate level numerical and statistical methods course for PhD-level bioengineers. In this article we share examples of this ChatGPT content, our observations on what worked best in our course, and speculate on how bioengineering students may be best served by this technology in the future.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"7 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relatively Rare Populations of Invasive Cells Drive Progression of Heterogeneous Tumors","authors":"Susan E. Leggett, Molly C. Brennan, Sophia Martinez, Joe Tien, Celeste M. Nelson","doi":"10.1007/s12195-023-00792-w","DOIUrl":"https://doi.org/10.1007/s12195-023-00792-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Breast tumors often display an astonishing degree of spatial and temporal heterogeneity, which are associated with cancer progression, drug resistance, and relapse. Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous subtype for which targeted therapies are scarce. Consequently, patients with TNBC have a poorer overall prognosis compared to other breast cancer patients. Within heterogeneous tumors, individual clonal subpopulations may exhibit differences in their rates of growth and degrees of invasiveness. We hypothesized that such phenotypic heterogeneity at the single-cell level may accelerate tumor progression by enhancing the overall growth and invasion of the entire tumor.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To test this hypothesis, we isolated and characterized clonal subpopulations with distinct morphologies and biomarker expression from the inherently heterogeneous 4T1 mouse mammary carcinoma cell line. We then leveraged a 3D microfluidic tumor model to reverse-engineer intratumoral heterogeneity and thus investigate how interactions between phenotypically distinct subpopulations affect tumor growth and invasion.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We found that the growth and invasion of multiclonal tumors were largely dictated by the presence of cells with epithelial and mesenchymal traits, respectively. The latter accelerated overall tumor invasion, even when these cells comprised less than 1% of the initial population. Consistently, tumor progression was delayed by selectively targeting the mesenchymal subpopulation.</p><h3 data-test=\"abstract-sub-heading\">Discussion</h3><p>This work reveals that highly invasive cells can dominate tumor phenotype and that specifically targeting these cells can slow the progression of heterogeneous tumors, which may help inform therapeutic approaches.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"12 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trisomy 21 Alters Cell Proliferation and Migration of iPSC-Derived Cardiomyocytes on Type VI Collagen","authors":"Rachel S. Reeser, Alyssa K. Salazar, Kendra M. Prutton, James R. Roede, Mitchell C. VeDepo, Jeffrey G. Jacot","doi":"10.1007/s12195-023-00791-x","DOIUrl":"https://doi.org/10.1007/s12195-023-00791-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Individuals with Down syndrome (DS) are 2000 times more likely to develop a congenital heart defect (CHD) than the typical population Freeman et al. in Am J Med Genet 80:213–217 (1998). The majority of CHDs in individuals with DS characteristically involve the atrioventricular (AV) canal, including the valves and the atrial or ventricular septum. Type VI collagen (COLVI) is the primary structural component in the developing septa and endocardial cushions, with two of the three genes encoding for COLVI located on human chromosome 21 and upregulated in Down syndrome (von Kaisenberg et al. in Obstet Gynecol 91:319–323, 1998; Gittenberger-De Groot et al. in Anatom Rec Part A 275:1109–1116, 2023).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To investigate the effect of COLVI dosage on cardiomyocytes with trisomy 21, induced pluripotent stem cells (iPSC) from individuals with DS and age- and sex-matched controls were differentiated into cardiomyocytes (iPSC-CM) and plated on varying concentrations of COLVI.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Real time quantitative PCR showed decreased expression of cardiac-specific genes of DS iPSC-CM lines compared to control iPSC-CM. As expected, DS iPSC-CM had increased expression of genes on chromosome 21, including <i>COL6A1</i>, <i>COL6A2</i>, as well as genes not located on chromosome 21, namely <i>COL6A3</i>, <i>HAS2</i> and <i>HYAL2</i>. We found that higher concentrations of COLVI result in decreased proliferation and migration of DS iPSC-CM, but not control iPSC-CM.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These results suggest that the increased expression of COLVI in DS may result in lower migration-driven elongation of endocardial cushions stemming from lower cell proliferation and migration, possibly contributing to the high incidence of CHD in the DS population.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139093636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}