Cytotherapy最新文献

{"title":"Characterization of immortalized bone marrow erythroid progenitor adult (imBMEP-A)-The first inducible immortalized red blood cell progenitor cell line derived from bone marrow CD71-positive cells.","authors":"Romy Kronstein-Wiedemann, Jessica Thiel, Duran Sürün, Madeleine Teichert, Stephan R Künzel, Stefan Zimmermann, Lisa Wagenführ, Frank Buchholz, Torsten Tonn","doi":"10.1016/j.jcyt.2024.06.009","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.06.009","url":null,"abstract":"<p><strong>Background aims: </strong>Ex vivo production of red blood cells (RBCs) represents a promising alternative for transfusion medicine. Several strategies have been described to generate erythroid cell lines from different sources, including embryonic, induced pluripotent, and hematopoietic stem cells. All these approaches have in common that they require elaborate differentiation cultures whereas the yield of enucleated RBCs is inefficient.</p><p><strong>Methods: </strong>We generated a human immortalized adult erythroid progenitor cell line derived from bone marrow CD71-positive erythroid progenitor cells (immortalized bone marrow erythroid progenitor adult, or imBMEP-A) by an inducible expression system, to shorten differentiation culture necessary for terminal erythroid differentiation. It is the first erythroid cell line that is generated from direct reticulocyte progenitors and demonstrates robust hemoglobin production in the immortalized state.</p><p><strong>Results: </strong>Morphologic analysis of the immortalized cells showed that the preferred cell type of the imBMEP-A line corresponds to hemoglobin-producing basophilic erythroblasts. In addition, we were able to generate a stable cell line from a single cell clone with the triple knockout of RhAG, RhDCE and KELL. After removal of doxycycline, part of the cells differentiated into normoblasts and reticulocytes within 5-7 days.</p><p><strong>Conclusions: </strong>Our results demonstrate that the imBMEP-A cell line can serve as a stable and straightforward modifiable platform for RBC engineering in the future.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604475","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":"Current challenges in cell and gene therapy: a joint view from the European Committee of the International Society for Cell & Gene Therapy (ISCT) and the European Society for Blood and Marrow Transplantation (EBMT)","authors":"Fermin Sanchez-Guijo ,&nbsp;Joaquim Vives ,&nbsp;Annalisa Ruggeri ,&nbsp;Christian Chabannon ,&nbsp;Selim Corbacioglu ,&nbsp;Harry Dolstra ,&nbsp;Dominique Farge ,&nbsp;Nico Gagelmann ,&nbsp;Claire Horgan ,&nbsp;Jurgen Kuball ,&nbsp;Benedicte Neven ,&nbsp;Tuula Rintala ,&nbsp;Vanderson Rocha ,&nbsp;Isabel Sanchez-Ortega ,&nbsp;John A. Snowden ,&nbsp;Jaap Jan Zwaginga ,&nbsp;Massimiliano Gnecchi ,&nbsp;Anna Sureda","doi":"10.1016/j.jcyt.2024.02.007","DOIUrl":"10.1016/j.jcyt.2024.02.007","url":null,"abstract":"<div><p>Cell and gene therapy poses evolving challenges. The current article summarizes the discussions held by European Regional Committee of the International Society for Cell &amp; Gene Therapy and the European Society for Blood and Marrow Transplantation (EBMT) on the current challenges in this field, focusing on the European setting. This article emphasizes the imperative assessment of real-world cell and gene therapy activity, advocating for expanded registries beyond hematopoietic transplantation and chimeric antigen receptor–T-cell therapy. Accreditation's role in ensuring standardized procedures, as exemplified by JACIE (The Joint Accreditation Committee of ISCT-Europe and EBMT), is crucial for safety. Access to commercial products and reimbursement variations among countries underscore the need for uniform access to advanced therapy medical products (ATMPs). Academic product development and point-of-care manufacturing face barriers to patient access. Hospital Exemption's potential, demonstrated by some initial experiences, may increase patient accessibility in individual situations. Regulatory challenges, including the ongoing European ATMPs legislation review, necessitate standardized criteria for Hospital Exemption and mandatory reporting within registries. Efforts to combat unproven therapies and fraud involve collaboration between scientific societies, regulatory bodies and patient groups. Finally, is important to highlight the vital role of education and workforce development in meeting the escalating demand for specialized professionals in the ATMP field. Collaboration among scientific societies, academic institutions, industry, regulatory bodies and patient groups is crucial for overcoming all these challenges to increase gene and cell therapy activity in Europe.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924000549/pdfft?md5=c4ebd1d0e80e1665bad0b332b64f4d1c&pid=1-s2.0-S1465324924000549-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925114","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":"Remembering Arnold Caplan","authors":"Katarina LeBlanc ,&nbsp;Mark Pittenger ,&nbsp;Ivan Martin ,&nbsp;Jacque Galipeau ,&nbsp;Edwin M. Horwitz ,&nbsp;Viswanathan Sowmya","doi":"10.1016/j.jcyt.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.06.004","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924007370/pdfft?md5=1ca56f5bea41514591604b229eae3956&pid=1-s2.0-S1465324924007370-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141582423","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":"Distinct effects of intravenous bone marrow-derived mesenchymal stem cell therapy on ischemic and non-ischemic lungs after ischemia-reperfusion injury","authors":"Julia Radicetti-Silva, Milena Oliveira, C. M. Baldavira, C. L. Braga, Renata Trabach Santos, N. S. Felix, Adriana Lopes Silva, V. Capelozzi, Fernanda Ferreira Cruz, Patricia Rieken Macedo Rocco, Pedro Leme Silva","doi":"10.1016/j.jcyt.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.07.009","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841613","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":"PD-1/PD-L1 interaction score and NKT-like cell infiltration predict immunotherapy efficacy in non-small cell lung cancer patients","authors":"Jing Zhang, Dong Lin, Huihua Hu, Haipeng Xu","doi":"10.1016/j.jcyt.2024.07.010","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.07.010","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846436","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":"Insights from CTTACC: immune system reset by cellular therapies for chronic illness after trauma, infection, and burn","authors":"Kenneth Bertram ,&nbsp;Charles Cox ,&nbsp;Hasan Alam ,&nbsp;Clifford Lowell ,&nbsp;Joseph Cuschieri ,&nbsp;Biju Parekkadan ,&nbsp;Shibani Pati","doi":"10.1016/j.jcyt.2024.02.013","DOIUrl":"10.1016/j.jcyt.2024.02.013","url":null,"abstract":"<div><h3>Background Aims</h3><p>In this paper, we present a review of several selected talks presented at the CTTACC conference (Cellular Therapies in Trauma and Critical Care) held in Scottsdale, AZ in May 2023. This conference review highlights the potential for cellular therapies to “reset” the dysregulated immune response and restore physiologic functions to normal. Improvements in medical care systems and technology have increasingly saved lives after major traumatic events. However, many of these patients have complicated post-traumatic sequelae, ranging from short-term multi-organ failure to chronic critical illness.</p></div><div><h3>Methods/Results</h3><p>Patients with chronic critical illness have been found to have dysregulated immune responses. These abnormal and harmful immune responses persist for years after the initial insult and can potentially be mitigated by treatment with cellular therapies.</p></div><div><h3>Conclusions</h3><p>The sessions emphasized the need for more research and clinical trials with cellular therapies for the treatment of a multitude of chronic illnesses: post-trauma, radiation injury, COVID-19, burns, traumatic brain injury (TBI) and other chronic infections.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010047","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":"Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States","authors":"Laura A. Adang ,&nbsp;Joshua L. Bonkowsky ,&nbsp;Jaap Jan Boelens ,&nbsp;Eric Mallack ,&nbsp;Rebecca Ahrens-Nicklas ,&nbsp;John A. Bernat ,&nbsp;Annette Bley ,&nbsp;Barbara Burton ,&nbsp;Alejandra Darling ,&nbsp;Florian Eichler ,&nbsp;Erik Eklund ,&nbsp;Lisa Emrick ,&nbsp;Maria Escolar ,&nbsp;Ali Fatemi ,&nbsp;Jamie L. Fraser ,&nbsp;Amy Gaviglio ,&nbsp;Stephanie Keller ,&nbsp;Marc C. Patterson ,&nbsp;Paul Orchard ,&nbsp;Jennifer Orthmann-Murphy ,&nbsp;Adeline Vanderver","doi":"10.1016/j.jcyt.2024.03.487","DOIUrl":"10.1016/j.jcyt.2024.03.487","url":null,"abstract":"<div><p>Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the <em>ARSA</em> (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617871","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":"Strategic infection prevention after genetically modified hematopoietic stem cell therapies: recommendations from the International Society for Cell & Gene Therapy Stem Cell Engineering Committee","authors":"Tami D. John ,&nbsp;Gabriela Maron ,&nbsp;Allistair Abraham ,&nbsp;Alice Bertaina ,&nbsp;Senthil Velan Bhoopalan ,&nbsp;Alan Bidgoli ,&nbsp;Carmem Bonfim ,&nbsp;Zane Coleman ,&nbsp;Amy DeZern ,&nbsp;Jingjing Li ,&nbsp;Chrystal Louis ,&nbsp;Joseph Oved ,&nbsp;Mara Pavel-Dinu ,&nbsp;Duncan Purtill ,&nbsp;Annalisa Ruggeri ,&nbsp;Athena Russell ,&nbsp;Robert Wynn ,&nbsp;Jaap Jan Boelens ,&nbsp;Susan Prockop ,&nbsp;Akshay Sharma","doi":"10.1016/j.jcyt.2024.02.005","DOIUrl":"10.1016/j.jcyt.2024.02.005","url":null,"abstract":"<div><p>There is lack of guidance for immune monitoring and infection prevention after administration of <em>ex vivo</em> genetically modified hematopoietic stem cell therapies (GMHSCT). We reviewed current infection prevention practices as reported by providers experienced with GMHSCTs across North America and Europe, and assessed potential immunologic compromise associated with the therapeutic process of GMHSCTs described to date. Based on these assessments, and with consensus from members of the International Society for Cell &amp; Gene Therapy (ISCT) Stem Cell Engineering Committee, we propose risk-adapted recommendations for immune monitoring, infection surveillance and prophylaxis, and revaccination after receipt of GMHSCTs. Disease-specific and GMHSCT-specific considerations should guide decision making for each therapy.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924000525/pdfft?md5=da9fe7fde8440b290f7637aa56a8a953&pid=1-s2.0-S1465324924000525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139928141","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":"The science and practice of current environmental risk assessment for gene therapy: a review","authors":"Frank Liu","doi":"10.1016/j.jcyt.2024.04.067","DOIUrl":"10.1016/j.jcyt.2024.04.067","url":null,"abstract":"<div><p>Gene therapy is a fast-growing field showing great potential to treat genetic diseases and cancer. With accelerating gene therapy development and approval, their environment risk assessment (ERA) becomes increasingly important. An ERA is an assessment of the risks to human health and the environment upon exposure to a medicinal product as the result of its release during clinical development or after entering the market. Because ERA is an important component of regulatory submission, drug developers must perform a robust assessment to ensure the safety of unintended persons, animal, plants, microorganisms and environment at large. Global regulations on gene therapy ERA continue to evolve. Gene therapy ERAs are carried out according to general principles as provided in regulatory guidelines for application of clinical trials and marketing authorizations. The current review intends to summarize regulations and content requirements on gene therapy ERA in European Union, the USA and Japan. The approved gene therapy products by EMA and US Food and Drug Administration are analyzed for the critical aspects of their ERAs to provide the current status and practice of gene therapy ERAs by drug developers. For this purpose, the main contents of these gene therapy ERAs are summarized. Critical safety factors of gene therapy ERAs are described. With more experience and knowledge to be accumulated, gene therapy ERAs are expected to be less challenging with commonly used viral vectors.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140782226","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":"Clinical grade multiparametric cell sorting and gene-marking of regulatory T cells","authors":"Adaeze Precious Ekwe ,&nbsp;Raymond Au ,&nbsp;Ping Zhang ,&nbsp;Benjamin A. McEnroe ,&nbsp;Mei Ling Tan ,&nbsp;Alda Saldan ,&nbsp;Andrea S. Henden ,&nbsp;Cheryl J. Hutchins ,&nbsp;Ashleigh Henderson ,&nbsp;Kari Mudie ,&nbsp;Keri Kerr ,&nbsp;Madonna Fuery ,&nbsp;Glen A. Kennedy ,&nbsp;Geoffrey R. Hill ,&nbsp;Siok-Keen Tey","doi":"10.1016/j.jcyt.2024.02.023","DOIUrl":"10.1016/j.jcyt.2024.02.023","url":null,"abstract":"<div><h3>Background aims</h3><p>Regulatory T cells (Tregs) are the main mediators of peripheral tolerance. Treg-directed therapy has shown promising results in preclinical studies of diverse immunopathologies. At present, the clinical applicability of adoptive Treg transfer is limited by difficulties in generating Tregs at sufficient cell dose and purity.</p></div><div><h3>Methods</h3><p>We developed a Good Manufacturing Practice (GMP) compliant method based on closed-system multiparametric Fluorescence-Activated Cell Sorting (FACS) to purify Tregs, which are then expanded <em>in vitro</em> and gene-marked with a clinical grade retroviral vector to enable <em>in vivo</em> fate tracking. Following small-scale optimization, we conducted four clinical-scale processing runs.</p></div><div><h3>Results</h3><p>We showed that Tregs could be enriched to 87– 92% purity following FACS-sorting, and expanded and transduced to yield clinically relevant cell dose of 136–732×10⁶ gene-marked cells, sufficient for a cell dose of at least 2 × 10⁶ cells/kg. The expanded Tregs were highly demethylated in the <em>FOXP3</em> Treg-specific demethylated region (TSDR), consistent with bona fide natural Tregs. They were suppressive <em>in vitro</em>, but a small percentage could secrete proinflammatory cytokines, including interferon-γ and interleukin-17A.</p></div><div><h3>Conclusions</h3><p>This study demonstrated the feasibility of isolating, expanding and gene-marking Tregs in clinical scale, thus paving the way for future phase I trials that will advance knowledge about the <em>in vivo</em> fate of transferred Tregs and its relationship with concomitant Treg-directed pharmacotherapy and clinical response.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140055411","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}