Best Practice & Research Clinical Haematology最新文献

{"title":"Endogenous and exogenous cytokines: An overview and introduction","authors":"Thomas R. Spitzer ,&nbsp;Hillard M. Lazarus","doi":"10.1016/j.beha.2025.101615","DOIUrl":"10.1016/j.beha.2025.101615","url":null,"abstract":"<div><div>Cytokines are ubiquitous small proteins, secreted by virtually all leukocytes and other immune effector cells, that interact with other cytokines and effector and regulatory cells to direct innate and adaptive immunity. Six broad categories of cytokines have been described, with functions ranging from stimulation of immunity and inflammation by cytokines produced by white blood cells (interleukins) to impacting the migration of immune effector cells to sites of inflammation and tissue injury (chemokines). When secreted in excess, or when there exists an imbalance between proinflammatory and anti-inflammatory cytokines, diseases ranging from sepsis to organ transplant rejection to autoimmune disorders occur. The development of exogenous cytokines for therapeutic use, similar or identical to naturally occurring cytokines, has resulted in advances in the management of cancer and autoimmune diseases. On the other hand, the development of inhibitors of cytokines has resulted in the ability to control of a growing list of inflammatory, neoplastic, autoimmune, and allergic conditions. Future investigations should continue to explore the manner cytokines are exploited for therapeutic purpose or are used as inhibitors to interrupt the pathobiological mechanisms of disease.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 2","pages":"Article 101615"},"PeriodicalIF":2.2,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844629","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":"Mesenchymal stem cells in hematology: Therapeutic initiatives and future directions","authors":"Portia Smallbone,&nbsp;Partow Kebriaei,&nbsp;Mayela Mendt,&nbsp;Elizabeth J. Shpall,&nbsp;Amanda L. Olson,&nbsp;Warren B. Fingrut","doi":"10.1016/j.beha.2025.101613","DOIUrl":"10.1016/j.beha.2025.101613","url":null,"abstract":"<div><div>In recent years, the landscape of hematology has undergone rapid transformation, driven by innovative therapeutic strategies harnessing the properties of novel cellular therapies. Mesenchymal stem cells (MSCs) represent one of these promising therapies, with potential applications across a range of hematologic conditions. These cells are notable for their immunomodulatory properties, key role in supporting the hematopoietic micro-environment and capacity for multi-directional differentiation. This review will focus on the biologic mechanisms underlying MSC therapeutic use, current avenues of clinical investigation, and potential challenges and future directions for MSC derived therapies.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101613"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684189","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}

{"title":"Creating a GMP cell processing program: A focus on quality and regulation","authors":"Darshan Patel ,&nbsp;Jane Reese Koç ,&nbsp;Folashade Otegbeye","doi":"10.1016/j.beha.2025.101614","DOIUrl":"10.1016/j.beha.2025.101614","url":null,"abstract":"<div><div>Implementing current Good Manufacturing Practice (GMP) regulations and principles even in early phases of cell-based therapy studies is crucial for ensuring safety and reproducible quality of these products. This paper outlines the comprehensive steps necessary to establish a robust GMP-compliant cell processing program in academic programs with emphases on adherence to regulatory and quality standards. While there are different regulatory agencies governing practice across the globe, the prevailing quality principles described here incorporate common requirements and guidelines from agencies such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The goal of this review is to provide guidance for developing a quality management program (QMP) that addresses all critical factors impacting each step in the cell therapy product lifecycle: from procurement and receipt of starter material, through manufacturing, testing, storage, distribution, and administration. The QMP should be designed to assure quality outcomes by maintaining qualified and trained staff at all levels as applicable to their job functions; establishing clear policies and procedures; ensuring the qualification of facilities and equipment; using qualified materials for human use; and providing a framework for detection of trends and implementing process improvement.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101614"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739110","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}

{"title":"Anti-GM-CSF autoantibodies in myeloid leukemias","authors":"Anna Sergeeva,&nbsp;Wingchi K. Leung,&nbsp;Lisa St John,&nbsp;Jeffrey J. Molldrem","doi":"10.1016/j.beha.2025.101611","DOIUrl":"10.1016/j.beha.2025.101611","url":null,"abstract":"<div><div>Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine integral to the differentiation, proliferation, and activation of various immune cells, especially those of myeloid lineage. Recombinant human GM-CSF (rhGM-CSF) plays a critical role after high-dose chemotherapy, hematopoietic cell transplantation, and high-dose irradiation by accelerating myeloid recovery and reducing the risk of severe infections. As an adjuvant in anti-tumor vaccines, rhGM-CSF stimulates the differentiation and activation of dendritic cells and promotes their recruitment to tumor sites.</div><div>Despite the therapeutic benefits, rhGM-CSF can induce the production of anti-GM-CSF-autoantibodies (GM-CSF-Ab) that have been implicated in rare diseases, such as autoimmune pulmonary alveolar proteinosis. These antibodies can neutralize GM-CSF activity, impairing macrophages and neutrophils. Furthermore, anti-GM-CSF-Ab have been linked to myeloid leukemias, where they are associated with active disease. The mechanisms behind anti-GM-CSF-Ab production and their role in disease progression remain poorly understood. This review article provides an overview of GM-CSF and anti-GM-CSF-Ab.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101611"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629545","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}

{"title":"Human mesenchymal stem cell therapy: Potential advances for reducing cystic fibrosis infection and organ inflammation","authors":"Tracey L. Bonfield ,&nbsp;Hillard M. Lazarus","doi":"10.1016/j.beha.2025.101602","DOIUrl":"10.1016/j.beha.2025.101602","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Innovation in cystic fibrosis (CF) supportive care, including implementing new antimicrobial agents, improved physiotherapy, and highly effective modulators therapy, has advanced patient survival into the 4th and 5th decades of life. However, even with these remarkable improvements in therapy, CF patients continue to suffer from pulmonary infection and other visceral organ complications associated with long-term deficient cystic fibrosis transmembrane conductance regulator (CFTR) expression. Human mesenchymal stem cells (MSCs) have been utilized in tissue engineering based upon their capacity to provide structural components of mesenchymal tissues. An alternative role of MSCs, however is their versatile utilization as cell-based infusion powerhouses due to the unique capacity to deliver milieu specific soluble biologic factors, promoting immune supportive antimicrobial and anti-inflammatory potency. MSCs derived from umbilical cord blood, bone marrow, adipose and other tissues can be expanded in &lt;em&gt;ex vivo&lt;/em&gt; using good manufacturing procedure facilities for a safe, unique therapeutic to reduce and limit CF infection and facilitate the resolution of multi-organ inflammation. In our efforts, we conducted extensive preclinical development and validation of an allogeneic derived bone marrow derived MSC product in preparation for a clinical trial in CF. In this process, potency models were developed to ensure the functional capacity of the MSC product to provide clinical benefit. &lt;em&gt;In vitro&lt;/em&gt;, murine &lt;em&gt;in vivo&lt;/em&gt; and patient tissue &lt;em&gt;ex vivo&lt;/em&gt; potency models were utilized to follow MSC anti-infective and anti-inflammatory potency associated with the CFTR deficient environment. We showed in our “First in CF” clinical trial that the allogeneic MSCs obtained from healthy volunteer bone marrow samples were safe. The advent of improved CF care measures and exciting new small molecules has changed the survival and morbidity phenotype of patients with CF, however, there are CF patients who cannot tolerate or have genotypes that are non-responsive to modulators. Additionally, even with the small molecule therapy, CF patients are living longer, but without genetic correction, with the CF disease manifestation aggravated by the continuance of pre-existing CFTR-associated clinical issues such as ongoing inflammation. MSCs secrete bio-active factors that enhance and protect tissue function and can promote “self-immune” regulation. These properties can provide therapeutic support for the traditional and changing face of CF disease clinical complications. Further, MSC-derived bio-active factors can directly mitigate colonizing pathogens' survival by producing antimicrobial peptides (AMPs) which change the pathogen surface and increase host recognition, elimination, and sensitivity to antibiotics. Herein, we review the potential of MSC therapeutics for treating many facets of CF, emphasizing the potential for providing great additive ther","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101602"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642649","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}

{"title":"The history of cytokines and growth factors development","authors":"Smith Kungwankiattichai ,&nbsp;Richard T. Maziarz","doi":"10.1016/j.beha.2025.101612","DOIUrl":"10.1016/j.beha.2025.101612","url":null,"abstract":"<div><div>The discovery and development of cytokines and growth factors represent transformative events in modern medicine, spanning from early observations of immune mediators to current therapeutic applications. This review chronicles the historical progression from the initial identification of permeability factors in 1926 to contemporary engineered cytokine therapeutics. Key milestones include the discovery of interferon (1957), the characterization of colony-stimulating factors, and the development of recombinant proteins in the 1980s. The field has evolved from basic understanding of immune communication to sophisticated therapeutic interventions, including targeted inhibitors and engineered cell therapies. While significant advances have been made in treating various diseases through cytokine modulation, challenges remain in managing pleiotropic effects and optimizing delivery systems. Recent innovations in bioengineering and cell therapy suggest promising directions for future therapeutic applications.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"38 1","pages":"Article 101612"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684082","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}

{"title":"Cytokines in hematopoietic cell transplantation and related cellular therapies","authors":"Abdul-Hamid Bazarbachi ,&nbsp;Markus Y. Mapara","doi":"10.1016/j.beha.2025.101600","DOIUrl":"10.1016/j.beha.2025.101600","url":null,"abstract":"<div><div>Cytokines are pleiotropic molecules involved in hematopoiesis, immune responses, infections, and inflammation. They play critical roles in hematopoietic cell transplantation (HCT) and immune effector cell (IEC) therapies, mediating both therapeutic and adverse effects. Thus, cytokines contribute to the immunopathology of graft-<em>versus</em>-host disease (GVHD), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). This review examines cytokine functions in these contexts, their influence on engraftment and immune recovery post-transplantation, and their role in mediating toxicities. We focus on current and potential uses of cytokines to enhance engraftment and potentiate IEC therapies, as well as strategies to mitigate cytokine-mediated complications using cytokine blockers (<em>e.g</em>., tocilizumab, anakinra) and JAK inhibitors (<em>e.g</em>., ruxolitinib). We discuss new insights into GVHD physiology that have led to novel treatments, such as CSF1R blockade, which is effective in refractory chronic GVHD.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101600"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551936","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":"CAR assembly line: Taking CAR T-cell manufacturing to the next level","authors":"Jiasheng Wang ,&nbsp;Paolo F. Caimi","doi":"10.1016/j.beha.2024.101595","DOIUrl":"10.1016/j.beha.2024.101595","url":null,"abstract":"<div><div>The widespread adoption of chimeric antigen receptor (CAR) T-cell therapy has been limited by complex, resource-intensive manufacturing processes. This review discusses the latest innovations aiming to improve and streamline CAR T-cell production across key steps like T-cell activation, genetic modification, expansion, and scaling. Promising techniques highlighted include generating CAR T cells from non-activated lymphocytes to retain a stem-like phenotype and function, non-viral gene transfer leveraging platforms like transposon and CRISPR, all-in-one fully automated bioreactors like the CliniMACS Prodigy and the Lonza Cocoon, rapid CAR T-cell manufacturing via abbreviating or eliminating <em>ex vivo</em> T-cell culture, implementing decentralized point-of-care automated manufacturing platforms, and optimizing centralized bioreactor infrastructure integrating end-to-end automation. Adoption of these emerging technologies can reduce production costs and timelines while enhancing product quality and accessibility. However, significant knowledge gaps persist regarding the feasibility, superiority, and optimal protocols for effectively incorporating many emerging techniques into widespread clinical practice. Further validation through clinical studies is still needed for many of these novel approaches.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101595"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143146264","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 reflection on Arnold Caplan, the father of MSC","authors":"James M. Anderson","doi":"10.1016/j.beha.2025.101597","DOIUrl":"10.1016/j.beha.2025.101597","url":null,"abstract":"<div><div>Arnold Caplan was the father of MSC, mesenchymal stem cells. His pioneering efforts have led to significant advances in the utilization of mesenchymal stem cells for the treatment of a wide variety of clinical diseases. This reflection provides some insight into Arnold's commitment to education and research regarding mesenchymal stem cells. Moreover, he was a good friend. Arnold will be missed.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101597"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551471","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":"Analyte heterogeneity analysis as a possible potency parameter for MSC","authors":"David Kaplan ,&nbsp;Eric Christian ,&nbsp;Sarah Planchon Pope ,&nbsp;Hillard M. Lazarus ,&nbsp;Jeffrey A. Cohen","doi":"10.1016/j.beha.2025.101596","DOIUrl":"10.1016/j.beha.2025.101596","url":null,"abstract":"<div><div>Mesenchymal stem/stromal cells (MSC) have been transplanted for therapeutic purposes with inconsistent results. MSC preparations are heterogeneous, and this person-to-person heterogeneity may account for the variable clinical outcomes. Additionally, the mechanisms of therapeutic action for MSC are unclear which confounds attempts to understand and identify factors that may account for variable clinical results. Here, we report our analysis of MSC preparations for the expression levels of molecules that have been hypothesized to mediate MSC function. Although most of the analytes assessed demonstrated little divergent expression, several molecules were found with enhanced heterogeneity both within individual MSC preparations and among MSC preparations from the sample of multiple sclerosis patients. The variable expression of these molecules may relate to the therapeutic heterogeneity of MSC. Additionally, we found a novel set of molecules that were highly intercorrelated in MSC. The tight association of this group of molecules may represent an invariant molecular organization that is integral to MSC activity. The precise analysis of molecular expression levels in MSC has the potential to answer concerns about variable therapeutic effects of MSC transplantation as well as to understand the mechanism of clinical effects.</div></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"37 4","pages":"Article 101596"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372935","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}