Cytotherapy最新文献

{"title":"Gene therapy for sickle cell disease: recent advances, clinical trials and future directions.","authors":"Josiah Ballantine, John F Tisdale","doi":"10.1016/j.jcyt.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.11.006","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is the most common inherited blood disorder worldwide, impacting millions and imposing severe healthcare challenges, particularly in resource-limited regions. Current treatments have variable efficacy and require lifelong adherence. Allogeneic Hematopoietic Stem Cell Transplantation can be curative but comes with significant side effects and limited donor availability limits its widespread applicability. Gene therapy, by addressing the root genetic causes, offers a revolutionary alternative. This article discusses the molecular mechanisms of SCD and β-thalassemia and highlights advancements in gene therapy, such as gene addition via lentiviral vectors and gene editing with CRISPR/Cas9 technology. Clinical trials have brought about significant progress but challenges remain, including leukemogenesis, delivery efficiency and cost. Future efforts must focus on enhancing efficiency, reducing costs, developing nongenotoxic conditioning regimens and methods for in vivo application.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900084","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":"Donor C1 Group KIR-ligand inferiority is linked to increased mortality in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide","authors":"Alexander Nikoloudis ,&nbsp;Anna Bauhofer ,&nbsp;Lena Griessl ,&nbsp;Anke Habermehl ,&nbsp;Christina Groiss ,&nbsp;Michaela Binder ,&nbsp;Robert Milanov ,&nbsp;Thomas Bauer ,&nbsp;Veronika Buxhofer-Ausch ,&nbsp;Christoph Aichinger ,&nbsp;Petra Hasengruber ,&nbsp;Emine Kaynak ,&nbsp;Dagmar Wipplinger ,&nbsp;Irene Strassl ,&nbsp;Olga Stiefel ,&nbsp;Andreas Petzer ,&nbsp;Holger Rumpold ,&nbsp;Sigrid Machherndl-Spandl ,&nbsp;Ansgar Weltermann ,&nbsp;Johannes Clausen","doi":"10.1016/j.jcyt.2024.12.003","DOIUrl":"10.1016/j.jcyt.2024.12.003","url":null,"abstract":"<div><h3>Background aims</h3><div>In HLA-identical hematopoietic stem cell transplantation (HSCT), HLA-C1 group killer cell immunoglobulin-like receptor (KIR) ligands have been linked to graft-versus-host disease, whereas C2 homozygosity was associated with increased relapses. The differential impact of the recipients versus the donor's HLA-C KIR ligands cannot be determined in HLA-identical HSCT but may be elucidated in the haploidentical setting, in which HLA-C (including the HLA-C KIR ligand group) mismatching is frequently present.</div></div><div><h3>Methods</h3><div>We retrospectively investigated the effect of recipient versus donor C1 ligand content on survival and complications in post-transplant cyclophosphamide (PTCy)–based haploidentical HSCT (n = 170). HSCTs were categorized as donor C1 supremacy (n = 34), C1 balance (n = 98), or donor C1 inferiority (n = 38).</div></div><div><h3>Results</h3><div>Following HSCT from C1-inferior donors, overall mortality (hazard ratio, 2.84; <em>P</em> = 0.002) and non-relapse mortality (sub-hazard ratio [SHR], 3.86; <em>P</em> = 0.007) were significantly increased. Following HSCT from C1-superior donors, a low 1-year relapse incidence and favorable 1-year progression-free survival were observed. C1 supremacy did not significantly impact acute or chronic graft-versus-host disease, natural killer cell reconstitution, or day 21 chimerism. Infection was a more common cause of death among recipients with a C1-inferior donor compared with C1-superior or C1-balanced donors.</div></div><div><h3>Conclusions</h3><div>These findings suggest an increased risk for NRM, particularly infection-related deaths, associated with C1-inferior donors. Upon independent confirmation, C1-inferior donors should be avoided in PTCy-based haploidentical HSCT.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 457-464"},"PeriodicalIF":3.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933461","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":"Autograft composition and outcome—towards an optimal graft?","authors":"Esa Jantunen ,&nbsp;Antti Turunen ,&nbsp;Anu Partanen","doi":"10.1016/j.jcyt.2024.12.007","DOIUrl":"10.1016/j.jcyt.2024.12.007","url":null,"abstract":"<div><div>The amount of CD34⁺ cells has been for decades the most important marker of autologous graft quality, but other graft cells, including various lymphocyte subsets, have gained some interest. This review attempts to summarize what is known about autograft cellular composition regarding post-transplant outcomes. The amount of CD34⁺ cells in the graft is associated with tempo of platelet recovery. It also has been associated with improved progression-free (PFS) and overall survival (OS) in many studies in patients with non-Hodgkin lymphoma and in some studies in patients with multiple myeloma. A greater number of lymphocytes in the graft has been linked with earlier lymphocyte recovery, which on the other hand has been associated with better post-transplant outcomes. In prospective studies, a greater number of T lymphocytes has been found to correlate with better PFS and OS in patients with non-Hodgkin lymphoma and multiple myeloma. Some studies also indicate that the number of natural killer cells in grafts is prognostically important. At present, it is challenging to define a so-called optimal graft in the autologous setting. In addition to adequate CD34⁺ cell counts, more lymphocytes also should be collected to achieve immune autografts, which may translate to improved patient outcomes. More data are needed regarding the functional status of various lymphocyte subset for post-transplant outcomes.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 493-499"},"PeriodicalIF":3.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933514","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":"Outcomes of allogeneic hematopoietic stem cell transplantation in Shwachman-Diamond syndrome: a systematic review and meta-analysis","authors":"Cuiping Ma ,&nbsp;Xiaohua Huang ,&nbsp;Yuhan Chen ,&nbsp;Fengqin Shi ,&nbsp;Xiao Li ,&nbsp;Shaodan Tian ,&nbsp;Wei Ma","doi":"10.1016/j.jcyt.2024.12.004","DOIUrl":"10.1016/j.jcyt.2024.12.004","url":null,"abstract":"<div><div>We conducted a systematic review and meta-analysis to evaluate the outcomes of Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in the treatment of Shwachman-Diamond syndrome (SDS). A literature search was performed on PubMed, Embase, and Web of Science. After screening 397 articles, 10 studies were included. Data was extracted in accordance with the PRISMA guidelines and analyzed using the R 'meta' package. The pooled median 3 (1–5)-year overall survival (OS) after Allo-HSCT were 63.7% (95% CI 56.9–70.2%), 80.3% (95% CI 68.% 5–92.1%), 41.1% (95% CI 21.7–60.4%), 48.9% (95% CI 29.0–68.9%), and 8.7% (95% CI 0.0–60.8%) in SDS patients, SDS patients with bone marrow failure (BMF), SDS patients with myeloid neoplasms (MN), SDS patients with myelodysplastic syndrome (MDS), and SDS patients with acute myeloid leukemia (AML), respectively. Allo-HSCT is an efficacious approach for treating SDS patients with severe hematologic complications. However, poor outcomes were revealed in SDS patients with MN with a pooled 3 (1–5)-year relapse rate (RR) after Allo-HSCT of 25.8% (95% CI 12.5–39.0%), and a pooled 3-year non-relapse mortality (NRM) was 52.6% (95% CI 34.2–70.9%). These findings were consistent with the clinical findings that transplant-related complications are the main cause of the poor transplantation prognosis of SDS patients with MN. Efficacious bone marrow conditioning regimens, graft-versus-host disease (GVHD) prevention, and bridging treatment regimens are potential means to improve the transplantation prognosis of SDS patients.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 465-474"},"PeriodicalIF":3.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916175","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":"Human keratinocytes grown at a gas-permeable interface in vitro stratify correctly to generate engineered human epidermis","authors":"Vaughan Feisst ,&nbsp;Lisa Y.Y. Zhou ,&nbsp;Chun-Jen Jennifer Chen ,&nbsp;Eloise Williams ,&nbsp;Elliott Dunn ,&nbsp;Inken Kelch ,&nbsp;Sarah Meidinger ,&nbsp;John M.T. Hunt ,&nbsp;Alex du Rand ,&nbsp;Heidi Robinson ,&nbsp;Saem M. Park ,&nbsp;Evert J. Loef ,&nbsp;Julian Lofts ,&nbsp;Hilary Sheppard ,&nbsp;Michelle Locke ,&nbsp;P. Rod Dunbar","doi":"10.1016/j.jcyt.2024.12.005","DOIUrl":"10.1016/j.jcyt.2024.12.005","url":null,"abstract":"<div><h3>Background</h3><div>One of the key functions of human skin is to provide a barrier, protecting the body from the surrounding environment and maintaining homeostasis of the internal environment. A mature, stratified epidermis is critical to achieve skin barrier function and is particularly important when producing skin grafts <em>in vitro</em> for wound treatment. For decades epidermal stratification has been achieved <em>in vitro</em> by culturing keratinocytes at an air-liquid interface, triggering proliferating basal keratinocytes to differentiate and form all epidermal layers.</div></div><div><h3>Results</h3><div>We show here that culturing keratinocytes at a gas-permeable interface can induce epidermal stratification equivalent to an air-liquid interface.</div></div><div><h3>Conclusions</h3><div>Culturing skin grafts at a gas-permeable interface has a number of advantages over the traditional air-liquid interface method including: less time input from highly skilled personnel, with consequent cost savings; fewer manipulations, with concomitant reduced risk of cell culture contamination; increased scalability of skin graft size; and improved potential for automation. These advantages confer significant benefits to the use of cell culture devices with gas-permeable interfaces to grow human skin for the treatment of major burns and other skin injuries.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 475-482"},"PeriodicalIF":3.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025497","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":"A successful haploidentical transplantation without conditioning regimen for a relapsed/refractory multiple myeloma patient after chimeric antigen receptor T-cell therapy","authors":"Zigang Dai ,&nbsp;Nanzhou Yu ,&nbsp;Yang Cao,&nbsp;Jianfeng Zhou,&nbsp;Yicheng Zhang,&nbsp;Na Wang,&nbsp;Xiaoxi Zhou","doi":"10.1016/j.jcyt.2024.10.005","DOIUrl":"10.1016/j.jcyt.2024.10.005","url":null,"abstract":"<div><h3>Background aims</h3><div>With novel therapies improving prognosis, the complications of multiple myeloma after multi-line treatment, particularly myelosuppression, have become a crucial determinant of long-term outcomes. Non-myeloablative allogeneic hematopoietic stem cell transplantation is a feasible option, but the transplant-related mortality rate remains high. Our study presents a relapsed/refractory multiple myeloma patient with a 9-year disease history.</div></div><div><h3>Methods</h3><div>The patient underwent multiple chemotherapy treatments and achieved partial remission. The patient then received two B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell treatments with lymphodepletion conditioning of fludarabine and cyclophosphamide.</div></div><div><h3>Results</h3><div>At the fifth month after the second CAR T-cell treatment, the patient achieved complete remission but developed refractory myelosuppression (grade 4 according to Common Terminology Criteria for Adverse Events 5.0) after several severe infections. In order to facilitate hematopoietic recovery, her daughter's stem cells were infused into her, which fortunately implanted without conditioning. After thrombotic microangiopathy and acute graft-versus-host disease, the patient was discharged with consistent full donor chimerism. We assume this engraftment may be attributed to the patient's severe hematopoietic failure and further host lymphodepletion by fludarabine.</div></div><div><h3>Conclusions</h3><div>This study highlights the potential of allogeneic hematopoietic stem cell transplantation with reduced conditioning intensity or even the omission of conditioning, particularly for a relapsed/refractory multiple myeloma patient who struggles with severe myelosuppression after long-term treatment.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 295-299"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900078","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":"Ganglioside expression delineates human mesenchymal stem/stromal cell populations derived from different tissue sources","authors":"Sophie Groux-Degroote ,&nbsp;Kyle Martin ,&nbsp;Nao Yamakawa ,&nbsp;Bernadette Coddeville ,&nbsp;Yann Guérardel ,&nbsp;Robert Sackstein","doi":"10.1016/j.jcyt.2024.12.001","DOIUrl":"10.1016/j.jcyt.2024.12.001","url":null,"abstract":"<div><div>Prior studies have indicated that human embryonic stem cells can be distinguished from those of other mammals based on variable expression of a class of membrane glycolipids known as glycosphingolipids (GSLs), raising the question as to whether GSL display could be utilized to phenotypically define subsets of human adult stem cell populations. Adult stem cells known as “mesenchymal stem/stromal cells” (MSCs) have shown immense promise in therapeutic applications for a variety of clinical indications. Most commonly, these cells are harnessed and then culture-expanded from bone-marrow (BM-MSCs) or from adipose tissue (A-MSCs) sources. Though operational differences exist between human BM-MSCs and A-MSCs, no surface markers have been characterized to date that distinguish these as distinct subsets of culture-expanded human adult stem cells. Accordingly, we isolated GSLs from primary cultures of marrow- and adipose-derived human MSCs and an unbiased screen was performed by mass spectrometry (via matrix-assisted laser desorption/ionization (MALDI)-quadrupole ion trap (QIT)-time-of-flight (TOF), hence, via “MALDI-QIT-TOF”) to analyze all component glycans. Flow cytometry was then undertaken to assess the relative levels of expression of MS-defined glycan determinants, followed by RT-qPCR to measure transcripts of genes encoding key enzymes involved in glycolipid biosynthesis. Notably, our data indicate that neither BM- nor A-MSCs display any significant level of either lacto-series or neolacto-series GSLs, but distinct differences exist in GSL species among A-MSCs and BM-MSCs: while both cell types express GSLs of the ganglio- and the globo-series, the ganglio-series GSLs GD3 and GD2 and the globo-series GSL SSEA-4 (also known as sialylGb5) are dominantly expressed only among human BM-MSCs. These structural features are shaped by divergent patterns of glycosyltransferase gene expression, with striking differences between BM- and A-MSCs in the expression of transcripts encoding GD3 synthase, GM2/GD2 synthase, and Gb5 synthase. Importantly, expression of GD3, GD2, and SSEA-4 is markedly diminished on differentiation of BM-MSCs, and co-cultures of A-MSCs and BM-MSCs show that the expression of GD3, GD2, and SSEA-4 is a cell-intrinsic feature of BM-MSCs. These data stratify the glycosignature(s) of human MSCs derived from different tissue sources, provide direct evidence that expression of these structures is cell stage-/lineage-specific, unveil the mechanistic basis of the differential expression of these glycan determinants, and draw attention to how knowledge of the MSC glycosignature can impact cytotherapeutic strategies.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 446-456"},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081991","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":"“Combined synergistic effects of concentrated growth factors and adipose-derived mesenchymal stem cells on regeneration of induced mandibular defects in rabbits”","authors":"Anas Ameer Khan ,&nbsp;Yue Wang ,&nbsp;Haiyang Li ,&nbsp;Xiaoyan Zhang ,&nbsp;Xiao Zhang ,&nbsp;Xudong Zhang ,&nbsp;Xiangjun Li","doi":"10.1016/j.jcyt.2024.12.006","DOIUrl":"10.1016/j.jcyt.2024.12.006","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to evaluate the potential of combining allogeneic adipose-derived mesenchymal stem cells (ADSCs) with autologous concentrated growth factors (CGF) to enhance the repair of mandibular defects in rabbits.</div></div><div><h3>Methods</h3><div>Rabbit ADSCs were characterized using flow cytometry, identifying CD73, CD90, and CD105 as surface markers, while Alizarin Red Staining confirmed osteogenic differentiation, showing substantial mineralized deposits by day 21. A total of 24 New Zealand white rabbits were divided into four groups: BLANK (control group), CGF, ADSCs, and ADSCs/CGF. Each rabbit underwent a standardized mandibular defect procedure, and assessments were conducted at 4 and 12 weeks post-surgery using Micro Computed Tomography (micro-CT) to evaluate bone volume and new bone formation, alongside Hematoxylin and Eosin (HE) staining for histological analysis.</div></div><div><h3>Results</h3><div>At 4 weeks, the CGF and ADSCs/CGF groups showed partial osteoid tissue formation, while the BLANK and ADSCs groups exhibited less osteoid tissue. By 12 weeks, the CGF and ADSCs/CGF groups demonstrated near-complete bone healing, with the ADSCs/CGF combination showing the most pronounced effects. Micro-CT and histological analyses confirmed significantly higher bone volume and new bone area ratios in the CGF, ADSCs, and ADSCs/CGF groups compared to the BLANK group, with the ADSCs/CGF group being the most effective (P&lt;0.05).</div></div><div><h3>Conclusion</h3><div>The findings demonstrate the synergistic potential of combining CGF with ADSCs to enhance bone regeneration in mandibular defects. The ADSCs/CGF combination offers superior outcomes compared to CGF or ADSCs alone, providing a strong foundation for further research and clinical applications in tissue engineering and regenerative medicine.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 483-492"},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682267","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":"Good Manufacturing Practice-grade fibronectin for hollow-fiber bioreactor cell manufacture: a mesenchymal stromal cell case study","authors":"Nathan D. Frank ,&nbsp;Ezequiel Zylberberg ,&nbsp;Mahajoub Bello Roufai ,&nbsp;Stuart L. Gibb ,&nbsp;Mindy M. Miller","doi":"10.1016/j.jcyt.2024.11.011","DOIUrl":"10.1016/j.jcyt.2024.11.011","url":null,"abstract":"<div><h3>Background aims</h3><div>The need for large-scale production of mesenchymal stromal cell (MSC)-based cellular therapeutics continues to grow around the globe. Manual cell expansion processes can be highly variable between operators, require significant hands-on time from skilled staff and, because of the large number of open manipulation steps required to produce cells in dose-relevant quantities, be prone to greater risk of contamination relative to automated processes. All of these can increase overall production costs and risks to the patient. In order to meet the needs of this growing industry, viable options for large-scale automation coupled with consistent and compliant ancillary materials needed to drive cell expansion are needed.</div></div><div><h3>Methods</h3><div>In the work described herein, the automated and functionally closed hollow-fiber bioreactor system Quantum Flex (Terumo Blood and Cell Technologies, Inc., Lakewood, CO, USA) was used in conjunction with Good Manufacturing Practice (GMP)-compliant, virus-inactivated human fibronectin (FN) from Akron Bio (Boca Raton, FL, USA) to expand MSCs to clinically relevant numbers. In order to assess the performance of Akron Bio's GMP-grade FN, use of this product in the production of MSCs was referenced against use of a research-use-only (RUO)-grade FN product used extensively for MSC expansion in Quantum. Because many MSC-based processes require passaging of cells to attain the appropriate number of cells needed, a two-passage process was employed comparing the transfer of MSCs expanded on RUO FN to RUO FN, GMP FN to GMP FN and RUO FN to GMP FN to assess the impacts of transitioning from one grade of FN to another, as a product might be required to do as it moves from pre-clinical to clinical stages and beyond.</div></div><div><h3>Results</h3><div>No statistically significant differences were noted when MSCs were transferred from RUO FN to RUO FN, GMP FN to GMP FN or RUO FN to GMP FN in terms of harvest yield, population doubling time, seeding efficiency estimates or fold expansion. All MSCs harvested from all groups met International Society for Cell &amp; Gene Therapy standards for MSCs in terms of protein marker expression measured by flow cytometry, adherence to plastic, downstream cell morphology and trilineage differentiation.</div></div><div><h3>Conclusions</h3><div>The combination of Quantum Flex as an expansion platform and Akron Bio's GMP FN is seen as an attractive option for larger-scale manufacture of GMP-grade MSC products.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 391-399"},"PeriodicalIF":3.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882679","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":"Considerations for manufacturing of cell and gene medicines for clinical development.","authors":"Mark W Lowdell","doi":"10.1016/j.jcyt.2024.11.015","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.11.015","url":null,"abstract":"<p><p>The global changes from 2001 that elevated substantially modified cell therapies to the definition of \"medicinal product\" have been the catalyst for the dramatic expansion of the field to its current and future commercial success. Europe was the first to incorporate human somatic cells into drug legislation with the medicines directive of 2001 (2001/83/EC), which led to the development of the term \"advanced therapy medicinal products\" (ATMPs) to cover all substantially modified products, tissue-engineered products and somatic cells that are not substantially modified but that are used non-homologously. For convenience, I use the term \"ATMPs\" throughout this review. The transition from \"cell therapy\" to \"cellular medicine\" coincided with changes in clinical trial legislation in Europe and, subsequently, across many drug jurisdictions throughout the world. As medicines, there is a clear path through multiple phases of trials and associated requirements for compliance with the good practice standards of drug development, and manufacturability is central to this development.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967399","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}