Cytotherapy最新文献

{"title":"TissueGene-C induces anti-inflammatory activity and M2 macrophage polarization via activation of prostaglandin E2 signaling","authors":"Huan Tran ,&nbsp;Wilma Tauro ,&nbsp;Ali Mobasheri ,&nbsp;Moon Jong Noh","doi":"10.1016/j.jcyt.2024.11.005","DOIUrl":"10.1016/j.jcyt.2024.11.005","url":null,"abstract":"<div><h3>Background and Aim</h3><div>Osteoarthritis (OA) is the most common form of degenerative joint disease that commonly affects the knees, hips and hands. OA is a mechano-inflammatory disease characterized by low-grade inflammation, which results in breakdown of the cartilage extracellular matrix within joints, leading to pain, stiffness and inflammation. TissueGene-C (TG-C) is a cell and gene therapy investigational drug for treating knee OA that comprises human allogeneic chondrocytes and an irradiated modified cell line stably expressing transforming growth factor beta 1 (TGF-β1). Previous pre-clinical animal studies have shown that TG-C provides pain relief via its anti-inflammatory effects and cartilage structural improvement in a rat OA model. The goal of this study was to investigate the mechanism of action of TG-C, explore its anti-inflammatory activity and identify the TG-C–derived active factor(s) responsible for its efficacy.</div></div><div><h3>Methods</h3><div>In this study, we utilized THP-1 cell line to develop an macrophage polarization model to test the anti-inflammatory activity of TG-C.</div></div><div><h3>Results</h3><div>Our data showed that TG-C induces the polarization of M2 macrophages and the upregulation of interleukin 10 (IL-10) and interleukin 1 receptor antagonist (IL-1ra) while inhibiting tumor necrosis factor alpha (TNF-α) expression. Additionally, this study identified prostaglandin E₂ (PGE₂) as the main bioactive factor responsible for the anti-inflammatory activity of TG-C.</div></div><div><h3>Conclusions</h3><div>Our results demonstrated that PGE₂ is expressed by the TG-C chondrocyte component and modulated by TGF-β1 derived from the second component of TG-C. Finally, the present study provides insight into the mechanism of action of TG-C in the treatment of OA.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 324-337"},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural stem cell–derived extracellular vesicles purified by monolith chromatography retain stimulatory effect in in vitro scratch assay","authors":"Ivano Luigi Colao ,&nbsp;Randolph L. Corteling ,&nbsp;Daniel G. Bracewell ,&nbsp;Ivan B. Wall","doi":"10.1016/j.jcyt.2024.11.007","DOIUrl":"10.1016/j.jcyt.2024.11.007","url":null,"abstract":"<div><h3>Background aims</h3><div>Extracellular vesicles (EVs) have gained traction as potential cell-free therapeutic candidates. Development of purification methods that are scalable and robust is a major focus of EV research. Yet there is still little in the literature that evaluates purification methods against potency of the EV product. In the present study, we examined two monolith chromatography methods with a focus on assessing the ability of purified EVs to retain stimulatory effects on fibroblasts to connect scalable purification methods with product outputs.</div></div><div><h3>Methods</h3><div>We characterized EVs recovered from CTX0E03 (CTX) neural stem cell–conditioned medium in terms of biomarker distribution, functional capacity and purity. We evaluated the ability of EVs to promote wound closure in an <em>in vitro</em> scratch assay prior to and following two monolith chromatography steps (anion exchange and hydrophobic interaction) to determine whether these options may better serve EV bioprocessing.</div></div><div><h3>Results</h3><div>EVs from CTX cells were successful in initiating wound repair in a fibroblast scratch assay over 72 h with a single 20-μg dose. EV preparations presented the markers CD9, CD81 and CD63 but also contained culture albumin and DNA as process impurities. EVs recovered by tangential flow filtration could be successfully purified further by both monolith chromatography steps. Post-monolith EV stimulation was conserved.</div></div><div><h3>Conclusions</h3><div>The results indicate that monolith chromatography is a viable purification method for EVs derived from cell culture that does not detract from the product's ability to stimulate fibroblasts, suggesting that product functionality is conserved. Further work is needed in developing suitable downstream processes and analytics to achieve clinically relevant purities for injectable biologics.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 365-377"},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid manufacture of low-seed CAR-T cells in a GMP-grade hollow-fiber bioreactor platform","authors":"Kurt Marshall ,&nbsp;Melissa Mastro ,&nbsp;Brian Nankervis ,&nbsp;Shahid Shahid ,&nbsp;Gabriella Ciasullo ,&nbsp;Trevor Smith ,&nbsp;Mary Loveras ,&nbsp;David Smith ,&nbsp;Mindy M. Miller ,&nbsp;Stuart L. Gibb","doi":"10.1016/j.jcyt.2024.11.003","DOIUrl":"10.1016/j.jcyt.2024.11.003","url":null,"abstract":"<div><div>Both quality of product and rapidity of manufacture are critical parameters if <em>ex vivo</em> manufacturing of autologous chimeric antigen receptor T cell (CAR-T) therapies is to reach its full potential. The Quantum Flex Cell Expansion System from Terumo Blood and Cell Technologies (Terumo BCT), a hollow-fiber bioreactor platform, is one of several cell expansion systems available to cell and gene therapy manufacturers to generate such cells in a GMP-compliant manner. In this study, the dynamic range of the Quantum Flex platform to expand CD19 CAR-T cells from variable quantities of starting material was investigated. Reflecting the industry's utilization of contract development manufacturing organizations (CDMOs) for accelerating clinical timelines, Terumo Blood and Cell Technologies performed a technology transfer of application protocols for study execution. Four different amounts of starting material (1, 3, 6 and 15 million cells) were expanded on Quantum Flex, using a unique donor's cells for each run. In this study, CAR-T cells were created using commercially obtained T cells and an anti-CD19 CAR-T lentiviral construct. The resultant heterogenous cell populations were expanded for 7 days in the functionally closed bioreactor platform. Expansion kinetics for all 4 starting material amounts were remarkedly similar, resulting in a 150- to 200-fold increase in cell numbers. This allowed for a study maximum of 2.6 billion cells from loading 15 million cells. Viability remained high throughout the expansion process with &gt;93% for all 4 donors at harvest. To complete the manufacturing cycle, the automated and functionally closed Finia Fill and Finish System (Terumo Blood and Cell Technologies, Lakewood, CO) was used to formulate the cells for cryopreservation. Postprocedure analysis for potency and cytotoxicity demonstrated the production of efficacious cells. With this range of starting numbers, the platform is relevant to adult, pediatric and compassionate CAR-T expansion dosing. Today, several platforms are available to achieve sufficient cell yields for therapeutic applications of CAR-T, and awareness of the capabilities, pros and cons of each platform is critical to drive progress.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 378-390"},"PeriodicalIF":3.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Particulates in CGT guidance survey results – an ISCT process development & manufacturing committee perspective on cell and gene therapy industry knowledge awareness","authors":"Nisha Durand ,&nbsp;Lindsay Davies ,&nbsp;Stephanie Davies ,&nbsp;Domhnall McGowan ,&nbsp;Dominic Clarke ,&nbsp;Steve Oh ,&nbsp;Dalip Sethi ,&nbsp;Sean Werner ,&nbsp;Samuel A. Molina ,&nbsp;Manufacturing Materials Safety & Technology Working Group (formerly the Particulate Working Group) within the ISCT Process Development & Manufacturing Committee","doi":"10.1016/j.jcyt.2024.10.004","DOIUrl":"10.1016/j.jcyt.2024.10.004","url":null,"abstract":"<div><div>The International Society for Cell &amp; Gene Therapy Particulates Working Group has surveyed the global industry on commonly used regulatory guidance documents pertaining to particulates across various cell and gene therapy (CGT) product-based chemistry and manufacturing controls. Responses were collated from academic and industrially based individuals involved in or making decisions for manufacturing, quality control and analytics. Two surveys covering therapy developers and manufacturing suppliers were created and distributed via e-mail, through focus groups and via social media platforms. In total, 97 responses were received from CGT professionals at different career levels, which varied from technicians to corporate executives. The responses represent a snapshot of the different CGT industries, with a bias in cell therapy developers, because of the distribution of respondents. Overall, we observed a widespread use of common guidance and legislative documents with specific testing requirements pinned to certain CGT product types. Cell-based combination drugs and devices are not well addressed and may require other guidance that was not referenced. These results indicate that CGT particulate risk management should be clarified by collating various particulate guidelines into an easy-to-use guide that brings awareness to the various legislative and guidance documents pertaining to new and novel therapies, their classification, their route of administration and the regulatory jurisdiction under which they are handled. The group also recommends clearly outlining the differences and similarities in particulate management regulations across the globe. As the CGT industry is undergoing maturation, the risk analysis methods are also maturing. With such a broad range in product types, routes of administration, source materials and processing methods, standards of risk analysis and control need to be specific to the risk profile associated with any given drug product. The manufacturing strategy of novel drug types represented under the advanced therapy umbrella will require careful interpretation and implementation of the existing guidance identified in this survey, as not one guidance covers all manufacturing challenges with particulates.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 287-294"},"PeriodicalIF":3.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(24)00870-3","DOIUrl":"10.1016/S1465-3249(24)00870-3","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"26 11","pages":"Page A5"},"PeriodicalIF":3.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(24)00867-3","DOIUrl":"10.1016/S1465-3249(24)00867-3","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"26 11","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Impact of delayed whole blood processing on the stability of infectious disease marker analytes during donor qualification for allogeneic cell therapies.’","authors":"J. Aho ,&nbsp;J. Schuster ,&nbsp;J. Wallace ,&nbsp;M. Bauer ,&nbsp;N. Amegashie ,&nbsp;E. Wiedenman ,&nbsp;J. Van Hulzen ,&nbsp;G. Quade ,&nbsp;J. Miller ,&nbsp;P. Caturegli","doi":"10.1016/j.jcyt.2024.09.002","DOIUrl":"10.1016/j.jcyt.2024.09.002","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"26 12","pages":"Page 1579"},"PeriodicalIF":3.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(24)00844-2","DOIUrl":"10.1016/S1465-3249(24)00844-2","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"26 10","pages":"Page A5"},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(24)00841-7","DOIUrl":"10.1016/S1465-3249(24)00841-7","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"26 10","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GMP-compliant extracellular vesicles derived from umbilical cord mesenchymal stromal cells: manufacturing and pre-clinical evaluation in ARDS treatment.","authors":"Zaquer Suzana Munhoz Costa-Ferro, Gisele Vieira Rocha, Katia Nunes da Silva, Bruno Diaz Paredes, Erick Correia Loiola, Johnatas Dutra Silva, John Lenon de Souza Santos, Rosane Borges Dias, Cláudio Pereira Figueira, Camila Indiani de Oliveira, Ludmilla David de Moura, Lígia Nunes de Morais Ribeiro, Eneida de Paula, Dalila Lucíola Zanette, Clarissa Araújo Gurgel Rocha, Patricia Rieken Macedo Rocco, Bruno Solano de Freitas Souza","doi":"10.1016/j.jcyt.2024.04.074","DOIUrl":"10.1016/j.jcyt.2024.04.074","url":null,"abstract":"<p><strong>Background aims: </strong>Extracellular vesicles (EVs) represent a new axis of intercellular communication that can be harnessed for therapeutic purposes, as cell-free therapies. The clinical application of mesenchymal stromal cell (MSC)-derived EVs, however, is still in its infancy and faces many challenges. The heterogeneity inherent to MSCs, differences among donors, tissue sources, and variations in manufacturing conditions may influence the release of EVs and their cargo, thus potentially affecting the quality and consistency of the final product. We investigated the influence of cell culture and conditioned medium harvesting conditions on the physicochemical and proteomic profile of human umbilical cord MSC-derived EVs (hUCMSC-EVs) produced under current good manufacturing practice (cGMP) standards. We also evaluated the efficiency of the protocol in terms of yield, purity, productivity, and expression of surface markers, and assessed the biodistribution, toxicity and potential efficacy of hUCMSC-EVs in pre-clinical studies using the LPS-induced acute lung injury model.</p><p><strong>Methods: </strong>hUCMSCs were isolated from a cord tissue, cultured, cryopreserved, and characterized at a cGMP facility. The conditioned medium was harvested at 24, 48, and 72 h after the addition of EV collection medium. Three conventional methods (nanoparticle tracking analysis, transmission electron microscopy, and nanoflow cytometry) and mass spectrometry were used to characterize hUCMSC-EVs. Safety (toxicity of single and repeated doses) and biodistribution were evaluated in naive mice after intravenous administration of the product. Efficacy was evaluated in an LPS-induced acute lung injury model.</p><p><strong>Results: </strong>hUCMSC-EVs were successfully isolated using a cGMP-compliant protocol. Comparison of hUCMSC-EVs purified from multiple harvests revealed progressive EV productivity and slight changes in the proteomic profile, presenting higher homogeneity at later timepoints of conditioned medium harvesting. Pooled hUCMSC-EVs showed a non-toxic profile after single and repeated intravenous administration to naive mice. Biodistribution studies demonstrated a major concentration in liver, spleen and lungs. HUCMSC-EVs reduced lung damage and inflammation in a model of LPS-induced acute lung injury.</p><p><strong>Conclusions: </strong>hUCMSC-EVs were successfully obtained following a cGMP-compliant protocol, with consistent characteristics and pre-clinical safety profile, supporting their future clinical development as cell-free therapies.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":"1013-1025"},"PeriodicalIF":3.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}