Meg A Schaefer, Adrian R Black, R Katherine Hyde, Daniel A Kuppers, Kyle J Hewitt
{"title":"Applications of the Human Bone Marrow Organoid System to Study Hematopoiesis and Anemia Stress.","authors":"Meg A Schaefer, Adrian R Black, R Katherine Hyde, Daniel A Kuppers, Kyle J Hewitt","doi":"10.1177/19373384261463760","DOIUrl":"10.1177/19373384261463760","url":null,"abstract":"<p><p>Hematopoietic stem and progenitor cells (HSPCs) are precisely organized within specialized bone marrow niches containing hematopoietic and nonhematopoietic cell types. Physiologically accurate human models of this niche environment that include functional HSPCs have been lacking until recently. Using induced pluripotent stem cells (iPSCs) grown in mixed-matrix hydrogels, vascularized three-dimensional human bone marrow organoids (hBMOs) can now be generated that contain mesenchymal, endothelial, and hematopoietic cells, all vital components of the bone marrow niche. While hBMOs have been shown to support engraftment of normal and malignant cells, there are numerous opportunities to use hBMOs for developing a wider experimental toolkit to test gene functions and stress responses. Here, we establish two new applications for the hBMO platform. First, we demonstrate successful engraftment of gene-edited CD34<sup>+</sup> cells from healthy donors, enabling direct investigation of gene-specific effects on human hematopoiesis in a defined microenvironment. Gene-edited engrafted HSPCs are maintained in hBMOs for 7 days and undergo multilineage differentiation. Second, we adapted a method to induce stress erythropoiesis-a response to acute anemia in mice and humans-in hBMOs, resulting in robust expansion of immunophenotypically defined hematopoietic progenitors and erythroid populations. These two advances expand the laboratory uses for hBMOs and establish this system as a versatile platform for studying human hematopoiesis and erythropoiesis, stress responses, and gene functions within a physiologically relevant bone marrow microenvironment.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"267-276"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424411","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}
MeyLign Long, Anita Touch, You Yang, Xiaohong Li, Zhun Xiao
{"title":"0.1% Peracetic Acid Treatment Is the Optimal Process for Ovarian Decellularized Extracellular Matrix.","authors":"MeyLign Long, Anita Touch, You Yang, Xiaohong Li, Zhun Xiao","doi":"10.1177/19373384261448318","DOIUrl":"10.1177/19373384261448318","url":null,"abstract":"<p><p>This research aimed to find the optimal sterilization process for ovarian decellularized extracellular matrix (OV-dECM). OV-dECM was prepared. Four different sterilization processes, such as ultraviolet ray, 1 mg/L CuCl<sub>2</sub> + 0.5% H<sub>2</sub>O<sub>2</sub>, 70% ethanol, and 0.1% peracetic acid (PAA), were evaluated. The sterilization efficiency and the <i>in vitro</i> and <i>in vivo</i> biocompatibility were assessed. Hematoxylin and eosin, 4',6-diamidino-2-phenylindole staining, and DNA quantitation indicated the successful production of OV-dECM. 0.1% PAA and 70% ethanol achieved better sterilization. The sterilized OV-dECM in the 70% ethanol and 0.1% PAA groups could integrate with human umbilical cord mesenchymal stem cell (between them: 7 days: <i>p</i> = 0.187; 10 days: <i>p</i> = 0.293; both <i>p</i> > 0.05) and keep the cell viability (CCK-8, cell counting kit-8) and cell morphology (F-actin staining). The sterilized OV-dECM in both 70% ethanol and 0.1% PAA groups had good CD31 (a neovascularization maker) fusion indexes (between them: <i>p</i> = 0.288; <i>p</i> > 0.05), while α-smooth muscle actin (another neovascularization maker) in the 0.1% PAA group was higher than that in the 70% ethanol group (between them: <i>p</i> = 0.012; <i>p</i> < 0.05). The assessment of CD68, CD86, and CD206 (macrophage phenotype makers) demonstrated that the 0.1% PAA group had better chance to promote the M1-M2 transformation of macrophage than 70% ethanol after the implantation of OV-dECM in mice. In conclusion, 0.1% PAA is the optimal sterilization process for OV-dECM with better sterilization capacity and biocompatibility.Impact StatementThis study identifies 0.1% peracetic acid as the optimal sterilization method for ovarian decellularized extracellular matrix (OV-dECM), resolving a critical barrier to artificial ovary (AO) development. It ensures OV-dECM sterility while preserving biocompatibility, promoting macrophage M1-to-M2 polarization to reduce inflammation. This advances AO translational potential, offering hope for fertility preservation in patients with cancer/leukemia and guiding standardized OV-dECM sterilization in regenerative medicine.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"215-229"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857262","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}
Muhammad Abid Sheikh, Ekhlass Mohammed, Tanya Golani, Mohammad El Mehairi, Bright Starling Emerald, Elhadi H Aburawi, Suraiya Anjum Ansari
{"title":"Generation and Characterization of Induced Pluripotent Stem Cell Line UAEUi001-A from an Emirati Patient with Ventricular Septal Defect.","authors":"Muhammad Abid Sheikh, Ekhlass Mohammed, Tanya Golani, Mohammad El Mehairi, Bright Starling Emerald, Elhadi H Aburawi, Suraiya Anjum Ansari","doi":"10.1177/19373384261458011","DOIUrl":"10.1177/19373384261458011","url":null,"abstract":"<p><p>The absence of induced pluripotent stem cell (iPSC) lines derived from Emirati patients with developmental disease hampers region-specific disease modeling and therapeutic research. Herein, we describe the creation of an iPSC line from peripheral blood mononuclear cells obtained from a 21-year-old Emirati female patient with ventricular septal defect (VSD) using Sendai virus-mediated delivery of reprogramming factors. The resulting line, UAEUi001-A, exhibited typical colony morphology, was mycoplasma negative, successfully generated embryoid bodies), and demonstrated strong alkaline phosphatase activity. These iPSCs were further characterized for pluripotency potential and their differentiation potential into the three germ layers under <i>in vitro</i> culture conditions through immunostaining using stage-specific markers. To the best our knowledge, this is the first reported generation of an iPSC line from an Emirati patient with VSD. Overall, this iPSC line may serve as a valuable model for establishing an Emirati-specific iPSC repository, supporting disease modeling and drug discovery relevant to the Emirati population.Impact StatementThis study establishes the first induced pluripotent stem cell (iPSC) line derived from an Emirati patient with ventricular septal defect, addressing a critical gap in region-specific disease models. It provides a valuable platform for understanding developmental cardiac disorders in underrepresented populations and supports the development of precision medicine and targeted therapeutic strategies relevant to the Emirati population.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"240-247"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240183","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}
Selina Banerjee, Ryan Brady, Lina Abu-Absi, Dylan Miller, Bryan Schellberg, Guohao Dai, Abigail Koppes, Ryan Koppes
{"title":"Design and Fabrication of Demountable 3D Microphysiological Systems.","authors":"Selina Banerjee, Ryan Brady, Lina Abu-Absi, Dylan Miller, Bryan Schellberg, Guohao Dai, Abigail Koppes, Ryan Koppes","doi":"10.1177/19373384261457992","DOIUrl":"10.1177/19373384261457992","url":null,"abstract":"<p><p>Several recent advances in microphysiological systems or organ-on-chip technology have demonstrated its potential for replacing traditional <i>in vitro</i> and animal models in the coming years. Despite the physiological relevance and cost-effectiveness of organ chips, there are several hurdles that must be overcome for widespread adoption for biological studies. Many manufacturing and scalability challenges have been overcome by a transition from polydimethylsiloxane to thermoplastics. However, challenges have arisen in these sealed, brittle systems related to end-point tissue analyses, harvest, and high-resolution imaging, which is particularly difficult for multilayer organ chips. Here, we present low-cost organ chips that are fluidically sealed but demountable, fabricated using a cut-and-assemble method without the need for cleanroom technologies. We have validated the capabilities of this method by demonstrating the culture of human aortic smooth muscle cells and induced pluripotent stem cell-derived neural cells, encapsulated in gelatin methacryloyl (GelMA) hydrogel on chip, for up to 27 days. The three-dimensional (3D) culture layer of the organ chip was removed, and high-resolution images were obtained following immunostaining. Furthermore, these organ chips facilitate rapid redesign and manufacture for alternative tissue and/or interface systems. To the best of our knowledge, this is the first innervated organ chip with multiple removable cell culture layers, as well as the first humanized nerve-artery model that includes a 3D hydrogel culture. In future work, these unique features of our platform can be utilized for investigating the crosstalk mechanisms between different cell types in coculture.Impact StatementWe present here a new method for fabricating low-cost demountable organ-on-a-chip platforms. This method leverages our recent cut-and-assemble method for layered three-dimensional organ chips comprised of gas impermeable thermoplastics.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"230-239"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240217","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}
Joshua Paciocco, Ahmed Hasan, Jason Chan, Daisuke Taniguchi, Satoshi Kamata, Cristina Amon, Golnaz Karoubi, Aimy Bazylak
{"title":"Automated Abnormal Vessel Detection in Re-Endothelialized Mouse Lungs: A Proof of Concept.","authors":"Joshua Paciocco, Ahmed Hasan, Jason Chan, Daisuke Taniguchi, Satoshi Kamata, Cristina Amon, Golnaz Karoubi, Aimy Bazylak","doi":"10.1177/19373384261458003","DOIUrl":"10.1177/19373384261458003","url":null,"abstract":"<p><p>Semantic segmentation was performed on 177 large histological images of re-endothelialized mouse lung vasculatures. Specifically, patch-based semantic segmentation algorithms were used to classify pixels corresponding to two classes: organ tissue, which includes lung and heart tissue; and ruptured and/or dilated vessels, which are abnormal vessels formed during re-endothelialization. Semantic segmentation is a potential means to automate the end-to-end analysis of these images, circumventing denoising and enhancement operations to visualize tissue and bypassing the manual diagnosis of ruptured and/or dilated vessels. To increase data quantity, images were compressed to sizes 1024 × 1024, 768 × 768, and 512 × 512 and then divided into nonoverlapping 256 × 256 patches. To benchmark the performance of the patch-based models, a vanilla model trained on complete images compressed to size 256 × 256 was also evaluated. The U-Net and LinkNet architectures were used to train and test each model using a data augmentation and transfer learning approach, and their results were ensembled. The loss of image context in the 3 × 3 and 4 × 4 patch-based models negatively impacted performance, generating many false positive predictions for target classes, whereas the low-image quantity of the vanilla model hindered performance. The 2 × 2 ensemble patch-based model returned the best performance, classifying organ tissue with a precision, recall, and intersection over union (IOU) of 88.0% ± 5.7%, 84.7% ± 9.2%, and 76.3% ± 10.9%, respectively, and classifying ruptured/dilated vessels with a precision, recall, and IOU of 78.4% ± 5.2%, 60.2% ± 11.4%, and 51.0% ± 8.4%, respectively.Impact StatementTo evaluate re-endothelization quality, the absence of ruptured and dilated vessels must be confirmed in the resultant re-endothelialized lung scaffold through subjective, work-intensive, and time-consuming per-image manual analysis. In this study, we apply computer vision to detect the ruptured and/or dilated vessels from re-endothelialized histology images via end-to-end semantic segmentation. We also investigate the viability of a patch-based semantic segmentation approach to detect ruptured and/or dilated vessels and generate high-resolution masks. Through this work, the potential of computer vision to automate and standardize the characterization of recellularized lung histology is demonstrated.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"248-259"},"PeriodicalIF":2.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206241","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":"Tissue-Engineered Brain-Mimetic Niches to Model Braintropic Triple-Negative Breast Cancer Metastasis.","authors":"Sam Freeman, John Slater","doi":"10.1177/19373384251404201","DOIUrl":"10.1177/19373384251404201","url":null,"abstract":"<p><p>Brain metastases of triple-negative breast cancer (TNBC) rapidly progress, causing severe neurological decline with a median survival of less than 6 months. This tragic disease is often difficult to identify with sufficient time for treatment and is exacerbated by a lack of effective pharmacological intervention. Replicating the biochemical and mechanical properties of the premetastatic niche <i>in vitro</i> is a critical step in expediting the development of new therapeutics. However, a high-fidelity and reproducible model system is needed. To quantify the influence of a brain-mimetic microenvironment on brain metastatic TNBC, we encapsulated and cultured the TNBC cell line, MDA-MB-231 (P231), and its braintropic subline, MDA-MB-231-BrM2a-831 (BrM2a), in three premetastatic niches: a highly cell-adhesive and highly cell-degradable permissive niche, a highly adhesive but less degradable niche, and a nonadhesive but highly degradable niche. To mimic brain extracellular matrix, we functionalized the adhesive formulations with a brain-mimetic peptide cocktail and compared the cell responses to a \"generic\" RGDS-functionalization. This suite of conditions allowed us to investigate the influences of integrin-mediated adhesion, cell-mediated degradation, and cell type on the fate of P231s and BrM2as. Our data demonstrate that brain-mimetic adhesion has little to no impact on P231 phenotype, but the BrM2as display reduced viable cell density, reduced proliferation, and a higher proportion of both spherical clusters and spherical individual cells compared with the \"generic\" RGDS-functionalized niches. This suggests that brain-mimetic adhesion signaling encourages a rounded, less invasive phenotype in BrM2as. Modeling pathological processes usingadvanced, biomimetic <i>in vitro</i> models that better replicate <i>in vivo</i> cell phenotype have the potentialtoenhanceimprove the outcome of preclinical therapeutic testing.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":"32 5","pages":"155-165"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006648","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}
Sheridan Fok, Anagha Shreesha, Angela Appiah-Kubi, Rebecca B Riggins, Brendan A C Harley
{"title":"The Size of Glioblastoma Spheroids Influences Patterns of Invasion and Temozolomide Efficacy.","authors":"Sheridan Fok, Anagha Shreesha, Angela Appiah-Kubi, Rebecca B Riggins, Brendan A C Harley","doi":"10.1177/19373384261432672","DOIUrl":"10.1177/19373384261432672","url":null,"abstract":"<p><p>Glioblastoma (GBM) is one of the most common malignant brain tumors, with patient mortality driven by invasion into the surrounding brain microenvironment and drug resistance. Multicellular spheroids are an increasingly common model to study GBM invasion and drug response in engineered biomaterials. However, a key design feature of tumor spheroid studies is the size of each spheroid (number of cells, diameter). Given the heterogeneous growth of GBM cells at the surgical margin, spheroids of different sizes may also have clinical relevance. Here, we define shifts in behavior and drug response of wild-type (WT) and temozolomide (TMZ)-resistant GBM spheroids as a function of initial spheroid size. GBM spheroids ranging from 1,000 to 10,000 cells in size were embedded into a methacrylamide-functionalized gelatin hydrogel. GBM spheroid size had an inverse relationship with the number of apoptotic cells. We observed significant spheroid-size-dependent effects on TMZ efficacy for both TMZ-resistant and WT cells. Interestingly, high single doses of TMZ were more effective in reducing three-dimensional migration from smaller spheroids than metronomic dosing, while high single dose and metronomic dosing were equally effective in reducing invasion for large TMZ-resistant spheroids. Our study highlights the importance of considering and reporting spheroid size for cancer tissue engineering studies considering invasion and drug resistance. It also informs future studies of residual GBM at the tumor margins most responsible for patient relapse and mortality.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"179-194"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina De Santiago, Andrea L Gardner, Patrik Parker, Joshua R Thomas, Gregory Callahan, Mrigayu Ghosh, Aaron B Baker, Amy Brock
{"title":"Clonal Lineage Tracing Reveals Distinct Invasive Subpopulations in Triple-Negative Breast Cancer.","authors":"Carolina De Santiago, Andrea L Gardner, Patrik Parker, Joshua R Thomas, Gregory Callahan, Mrigayu Ghosh, Aaron B Baker, Amy Brock","doi":"10.1177/19373384261432668","DOIUrl":"10.1177/19373384261432668","url":null,"abstract":"<p><p>Metastatic dissemination in triple-negative breast cancer (TNBC) arises from extensive intratumoral heterogeneity, yet the clonal and transcriptional programs that underlie invasive behavior remain poorly defined. The field lacks experimental systems capable of simultaneously tracking the clonal identity and transcriptional state of invasive subpopulations. Here, we apply a clonal lineage-tracing platform coupled with single-cell RNA sequencing to resolve how subpopulations contribute to invasion in a model of TNBC. We demonstrate that invasion is driven by a subset of recurrent clones, indicating the presence of pre-existing subpopulations intrinsically primed for migratory behavior. Transcriptomic profiling further reveals two transcriptomically distinct invasive cell states that remain stable across independent selections. Targeted perturbations suppress these dominant invasive programs but enable invasion by alternative rare clones, demonstrating compensatory clonal dynamics in response to selective pressure. Together these findings show that invasive potential arises from stable clonal programs and that heterogenous tumors maintain invasive capacity through clonal replacement. Clonally resolved single-cell profiling provides a framework for dissecting invasive heterogeneity and highlights the need for therapeutic strategies that account for clone-specific behaviors and the dynamic restructuring of tumor subpopulations.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"166-178"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843123","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}
Suzanne Lightsey, Heather R Kates, Kalyanee Shirlekar, Jason O Brant, Blanka Sharma
{"title":"A Defined 3D Hydrogel Model Recapitulates Key Transcriptomic Features of Lung Adenocarcinoma.","authors":"Suzanne Lightsey, Heather R Kates, Kalyanee Shirlekar, Jason O Brant, Blanka Sharma","doi":"10.1177/19373384261448311","DOIUrl":"10.1177/19373384261448311","url":null,"abstract":"<p><p>Three-dimensional (3D) culture systems have emerged as powerful tools to model tumor biology and bridge the gap between conventional two-dimensional (2D) assays and <i>in vivo</i> studies. Here, we evaluate a poly(ethylene glycol)-based hydrogel as a simplified yet functionally relevant platform for modeling premalignant lung adenocarcinoma using the A549 cell line. Cells cultured in hydrogels exhibited transcriptional profiles that more closely resembled xenograft tumors than conventional 2D monolayers. Pathway-level analysis and regression-based benchmarking revealed restoration of critical hallmark programs, including proliferation, immune signaling, developmental pathways, and stress response cascades. While the 3D model does not fully recapitulate the complexity of the tumor microenvironment, its chemically defined, tunable, and reproducible design offers an accessible, physiologically informative model of lung adenocarcinoma that restores key transcriptional and functional features lost in conventional culture systems.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":"32 5","pages":"195-207"},"PeriodicalIF":2.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006597","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}
Ceri-Anne E Suurmond, Natasja W M van Dijk, René van Rheden, Vincent M J I Cuijpers, Ewald M Bronkhorst, Mani Diba, Sander C G Leeuwenburgh, Jeroen J J P van den Beucken
{"title":"A Humanized Bone Metastasis Model: <i>Ex Vivo</i> and <i>In Vivo</i> Applications.","authors":"Ceri-Anne E Suurmond, Natasja W M van Dijk, René van Rheden, Vincent M J I Cuijpers, Ewald M Bronkhorst, Mani Diba, Sander C G Leeuwenburgh, Jeroen J J P van den Beucken","doi":"10.1177/19373384261422836","DOIUrl":"10.1177/19373384261422836","url":null,"abstract":"<p><p>Patients with breast or prostate cancer have a high chance of developing bone metastasis, which is associated with many skeletal-related events. The development of novel bone metastasis treatments is lagging behind due to the lack of reliable models. We aimed to develop a humanized bone metastasis model comprising vital human bone discs and human metastatic cancer cells (bone metastasis discs), which were subsequently cultured <i>ex vivo</i> or subcutaneously implanted into nude mice. <i>Ex vivo</i> culture experiments confirmed that cells within the bone metastasis discs remained metabolically active, while the presence of metastatic cancer cells could be monitored using bioluminescence. Although histological analyses confirmed the presence of relevant bone cells in the human bone tissue, no apparent formation of metastatic lesions was detected over the 2-week <i>ex vivo</i> culture period. In contrast, subcutaneously implanted bone metastasis discs demonstrated clear metastatic lesion formation, with osteolytic characteristics, that progressed from 3 to 6 weeks after implantation for both breast and prostate cancer bone metastasis discs. Histologically, healthy bone tissue with bone marrow compartments as well as anastomosis was observed. Cisplatin treatment of <i>ex vivo</i> cultured bone metastasis discs significantly decreased the bioluminescent signal from (prostate) cancer cells, while no effects of cisplatin treatment were observed for <i>in vivo</i> implanted bone metastasis discs. Our data provide a proof of concept for an <i>ex vivo</i>/<i>in vivo</i> bone metastasis model with vital human bone and human metastatic cancer cells but require further fine-tuning to improve robustness, relevance, and quantification methods. Future research could potentially use these models for the evaluation of novel bone metastasis treatments, accelerating their potential clinical application.</p>","PeriodicalId":23154,"journal":{"name":"Tissue engineering. Part C, Methods","volume":" ","pages":"121-137"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318260","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}