{"title":"Primary Human Cell-Derived Extracellular Matrix from Decellularized Fibroblast Microtissues with Tissue-Dependent Composition and Microstructure","authors":"Vera C. Fonseca, Vivian Van, Blanche C. Ip","doi":"10.1007/s12195-024-00809-y","DOIUrl":"https://doi.org/10.1007/s12195-024-00809-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Human extracellular matrix (ECM) exhibits complex protein composition and architecture depending on tissue and disease state, which remains challenging to reverse engineer. One promising approach is based on cell-secreted ECM from primary human fibroblasts that can be decellularized into acellular biomaterials. However, fibroblasts cultured on rigid culture plastic or biomaterial scaffolds can experience aberrant mechanical cues that perturb the biochemical, mechanical, and the efficiency of ECM production.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Here, we demonstrate a method for preparing decellularized ECM using primary human fibroblasts with tissue and disease-specific features with two case studies: (1) cardiac fibroblasts; (2) lung fibroblasts from healthy or diseased donors. Cells aggregate into engineered microtissues in low adhesion microwells that deposited ECM and can be decellularized. We systematically investigate microtissue morphology, matrix architecture, and mechanical properties, along with transcriptomic and proteomic analysis.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Microtissues exhibited tissue-specific gene expression and proteomics profiling, with ECM complexity similar to native tissues. Healthy lung microtissues exhibited web-like fibrillar collagen compared to dense patches in healthy heart microtissues. Diseased lung exhibited more disrupted collagen architecture than healthy. Decellularized microtissues had tissue-specific mechanical stiffness that was physiologically relevant. Importantly, decellularized microtissues supported viability and proliferation of human cells.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>We show that engineered microtissues of primary human fibroblasts seeded in low-adhesion microwells can be decellularized to produce human, tissue and disease-specific ECM. This approach should be widely applicable for generating personalized matrix that recapitulate tissues and disease states, relevant for culturing patient cells ex vivo as well as implantation for therapeutic treatments.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550963","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 Label-Free Colorimetric AuNP-Aptasensor for the Rapid Detection of Vibrio cholerae O139","authors":"Masilamani Karthikeyan, Pasupathi Rathinasabapathi","doi":"10.1007/s12195-024-00804-3","DOIUrl":"https://doi.org/10.1007/s12195-024-00804-3","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141342373","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}
Chloe P. Whitworth, W. Y. Aw, Elizabeth L. Doherty, Chenchen Handler, Y. Ambekar, Aanya Sawhney, G. Scarcelli, W. Polacheck
{"title":"P300 Modulates Endothelial Mechanotransduction of Fluid Shear Stress","authors":"Chloe P. Whitworth, W. Y. Aw, Elizabeth L. Doherty, Chenchen Handler, Y. Ambekar, Aanya Sawhney, G. Scarcelli, W. Polacheck","doi":"10.1007/s12195-024-00805-2","DOIUrl":"https://doi.org/10.1007/s12195-024-00805-2","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141357791","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}
A. Denisin, Honesty Kim, Ingmar H. Riedel-Kruse, Beth l. Pruitt
{"title":"Field Guide to Traction Force Microscopy","authors":"A. Denisin, Honesty Kim, Ingmar H. Riedel-Kruse, Beth l. Pruitt","doi":"10.1007/s12195-024-00801-6","DOIUrl":"https://doi.org/10.1007/s12195-024-00801-6","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140671309","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":"Perspectives on Incorporating a Large Language Model into a Cellular and Molecular Bioengineering Graduate Course","authors":"David A. Rubenstein, Carsi Kim","doi":"10.1007/s12195-024-00802-5","DOIUrl":"https://doi.org/10.1007/s12195-024-00802-5","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688327","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":"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}