Cytotherapy最新文献

{"title":"Outcome of donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation in relapsed myelodysplastic syndrome.","authors":"Atsushi Marumo, Yasunobu Nagata, Machiko Fujioka, Shuhei Kurosawa, Yuho Najima, Emiko Sakaida, Noriko Doki, Kentaro Fukushima, Shuichi Ota, Katsuhiro Shono, Ayumu Ito, Naoyuki Uchida, Tetsuya Nishida, Masashi Sawa, Hiroko Tsunemine, Ken-Ichi Matsuoka, Onizuka Makoto, Yoshinobu Kanda, Takahiro Fukuda, Yoshiko Atsuta, Hidehiro Itonaga","doi":"10.1016/j.jcyt.2024.09.006","DOIUrl":"10.1016/j.jcyt.2024.09.006","url":null,"abstract":"<p><strong>Background aims: </strong>Allogeneic hematopoietic stem cell transplantation (HSCT) improves outcomes for myelodysplastic syndrome (MDS) patients, but relapse rates remain high, and postrelapse treatment options are limited. Therefore, this study aimed to identify the factors contributing to the response to donor lymphocyte infusion (DLI) in relapsed MDS patients post-HSCT.</p><p><strong>Methods: </strong>This study included 107 patients with relapsed and DLI-treated MDS who underwent their first HSCT between 2002 and 2022 and were registered in the Transplant Registry Unified Program. Univariate and multivariate survival analyses were conducted using log-rank tests and Cox proportional hazards models. Overall survival (OS) and response rates to DLI were also analyzed.</p><p><strong>Results: </strong>The 1-year OS was 30.0% and univariate analysis identified poor prognostic factors: age ≥58 years (P = 0.003), complex karyotype (P = 0.026), hematologic relapse (P = 0.026) and early relapse (P = 0.004). Azacitidine plus DLI also improved prognosis (P < 0.001). Multivariate analysis confirmed age ≥58 years, hematologic relapse, and early relapse as poor prognostic factors. The adjusted OS for patients aged ≥58 years who relapsed <110 days post-transplant showed that the 1-year OS in patients with cytogenetic/molecular relapse was 43.6%, compared to 9.4% for those with hematologic relapse. Acute graft-versus-host disease (GVHD) occurred in 62.3% of patients, and chronic GVHD in 30.8%, with manageable outcomes.</p><p><strong>Conclusions: </strong>DLI may improve OS in younger patients, those with cytogenetic/molecular relapse, and those with late relapse. Despite the risk of GVHD, its impact on prognosis is minimal. Given the limited treatment options, DLI should be considered for relapsed MDS patients post-HSCT.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584712","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":"Efficacy of a single dose of cryopreserved human umbilical cord mesenchymal stromal cells for the treatment of knee osteoarthritis:a randomized, controlled, double-blind pilot study.","authors":"Omar Amado Pico, Francisco Espinoza, María Ignacia Cádiz, Claudia L Sossa, Silvia M Becerra-Bayona, María C Canencio Salgado, Javier Eduardo Rengifo Rodríguez, Oscar Fabian Valdivieso Cárdenas, Johanna Marcela Quintero Cure, Maroun Khoury, Martha L Arango-Rodríguez","doi":"10.1016/j.jcyt.2024.09.005","DOIUrl":"10.1016/j.jcyt.2024.09.005","url":null,"abstract":"<p><strong>Background: </strong>Knee osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disorder, which is particularly common in older population. While conventional treatments have limited effectiveness, the development of more effective therapeutic strategies is necessary to address this primary source of pain and disability. Umbilical cord mesenchymal stromal cells (UC-MSCs) offer a promising therapeutic approach for treating knee OA.</p><p><strong>Aim: </strong>This randomized, prospective, double-blind and controlled pilot study was carried out to evaluate and compare the safety and therapeutic efficacy of a single intra-articular injection of a standardized product CellistemOA (5 × 10⁶ ± 5 × 10⁵ UC-MSCs), vs. triamcinolone (a synthetic corticosteroid) (10 mg/mL) in thirty patients with symptomatic knee OA (Kellgren-Lawrence grade II or III).</p><p><strong>Methods: </strong>The outcomes included changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores based on a Likert scale, numerical rating score (NRS) for pain, Magnetic Resonance Imaging (MRI), and quality of life (SF-36 questionnaire), from baseline and throughout 12-months of follow-up.</p><p><strong>Results: </strong>Patients treated with CellistemOA showed significant improvement in WOMAC score (including the three subscale scores (pain, stiffness and function), NRS in pain, and SF-36 profile from baseline to 12 months (p < 0.05) compared to the triamcinolone group, and no severe adverse events were reported. There were no significant differences in MRI WORMS scores between the two groups. However, patients who received the cellular treatment experienced a significant improvement in their SF-36 profile (p < 0.05).</p><p><strong>Conclusions: </strong>This pilot study revealed that a single dose of CellistemOA is safe and superior to the active comparator in knee OA at 1-year of follow-up, making it a compelling therapeutic alternative to treat symptomatic OA patients.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584632","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":null,"pages":null},"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":null,"pages":null},"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":"Enumeration and gentle sorting of immune cells on chip, key to next generation advanced therapies in outpatient setting.","authors":"Sarah Libbrecht, Koen de Wijs, Chengxun Liu, Liesbet Lagae","doi":"10.1016/j.jcyt.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.10.002","url":null,"abstract":"<p><strong>Background: </strong>A thorough understanding of immune-oncology and molecular medicine has been vital in the development of cell therapeutics. At the basis of this translational research and its future implementation into a medicinal product, lies the availability of pure and viable cell populations. Currently, FACS and magnetic bead isolation are successfully used but suffer to fulfill all requirements. FACS is costly and difficult to upscale due to the limitation of shear stress, especially fragile, cells can handle. Therefore, magnetic bead isolation is often used as it is gentler, but it lacks the multiparametric aspect to isolate more complex cellular profiles.</p><p><strong>Aims: </strong>We aim to develop a versatile technology able of multi marker detection and isolation of complex cell types with high purity, viability and throughput.</p><p><strong>Methods: </strong>We have developed a gentle sorting mechanism based on a jet flow created by micro vapor bubbles, enabling a closed microfluidic cell isolation platform capable of multiparametric sorting with high viability, purity and throughput. In this work we compared the purity, recovery and viability of sorted CD4+ CD14- cells to magnetic isolation, most often used for other cell manufacturing approaches. Futhermore, we cultured the sorted cells of both isolation strategies and compared their growth curve and expression of activation-induced IL2 and IFN-γ.</p><p><strong>Results: </strong>We demonstrate that this tool can achieve a pure population of CD4+ CD14- cells with high viability after sorting without compromising the recovery. On top of the viability also the growth and activation potential of sorted cells is unhampered by comparison to the benchmark gentle magnetic isolation.</p><p><strong>Conclusions: </strong>Our technology allows for the development of a compact system which sets it apart from other efforts intended to create automated cell therapeutic solutions.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548680","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":"Enriching central memory T cells using novel bioreactor design for T cell manufacturing.","authors":"Sixun Chen, Akshaya V Prabhu, Ahmad Amirul Bin Abdul Rahim, Kang-Zheng Lee, Dan Liu","doi":"10.1016/j.jcyt.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.10.001","url":null,"abstract":"<p><strong>Background: </strong>The manufacturing of T cell therapies aims to achieve high yields of product with potent phenotypes. We have developed a novel bioreactor, bioreactor with expandable culture area-dual chamber (BECA-D), which has previously demonstrated functionality for scaled T cell manufacturing.</p><p><strong>Methods and results: </strong>Methods and Results: In this study, incorporation of a stirring mechanism into the double-chamber bioreactor design was tested to homogenize the media components between the two chambers. In addition to the improved media homogenization, the stirring culture was observed to have higher yield and enrichment of central memory T cells, a T cell subpopulation that has been associated with improved therapeutic efficacy compared with a static control. BECA-D with a stirring mechanism was evaluated for its performance in culturing T cells in comparison with a static control, BECA-D, and an industry benchmark, G-Rex10 (Wilson Wolf Manufacturing). BECA-D with a stirring mechanism was able to preferentially promote the enrichment of central memory T cells compared with the static cultures, indicative of the effect of the stirring mechanism.</p><p><strong>Conclusion: </strong>By achieving high T cell yields with a favorable subpopulation profile, the mechanical method of incorporating stirring into a double-chamber bioreactor such as BECA-D carries great potential as a useful research and manufacturing tool to support advanced T-cell therapy manufacturing.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479807","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":"Using qPCR and ddPCR to study biodistribution of cell therapy products: a multi-site evaluation.","authors":"Eriko Fujita, Syunsuke Yamamoto, Takeshi Hanada, Shingo Jogasaki, Yoshiyuki Koga, Yukinori Yatsuda, Yoshiyuki Kakizaki, Yoshinori Jo, Yuya Asano, Koichi Yonezawa, Yuu Moriya, Miyu Nakayama, Yukiko Arimura, Yurie Okawa, Hiroyuki Komatsu, Masahiko Ito, Syunsuke Suzuki, Takuya Kuroda, Satoshi Yasuda, Yoshiteru Kamiyama, Yoji Sato","doi":"10.1016/j.jcyt.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.09.003","url":null,"abstract":"<p><strong>Backgroud aims: </strong>Regenerative therapies employing cell therapy products (CTPs) have attracted considerable attention. Biodistribution (BD) evaluation of CTPs is mainly performed to clarify the cell survival time, engraftment, and distribution site. This evaluation is crucial for predicting the efficacy and safety profiles of clinical studies based on non-clinical BD study outcomes. However, no internationally unified method has been established for assessing cell BD after administration. Here, we aimed to standardize the BD assay method used for CTPs, conducting the following evaluations using the same protocol across multiple study facilities: (1) in vitro validation of quantitative polymerase chain reaction (qPCR) and droplet digital PCR (ddPCR) analyses using the primate-specific Alu gene, and (2) in vivo BD studies after the intravenous administration of human mesenchymal stem cells (hMSCs) to immunodeficient mice, commonly used in non-clinical tumorigenicity studies.</p><p><strong>Methods: </strong>Quality control samples were prepared and analyzed by adding a fixed number of human-derived cells to several mouse tissues. The respective quantitative performances of the qPCR and ddPCR methods were compared for accuracy and precision. hMSCs were intravenously administered to immunodeficient mice, and tissues were collected at 1, 4, and 24 h after administration.</p><p><strong>Results: </strong>Both methods demonstrated an accuracy (relative error) generally within ±50% and a precision (coefficient of variation) generally less than 50%. While differences in calibration curve ranges were observed between qPCR and ddPCR, no significant differences in quantification were found among the assay facilities. The BD of hMSCs in mice was evaluated at seven facilities (qPCR at three facilities; ddPCR at four facilities), revealing similar tissue distribution profiles in all facilities, with the lungs showing the highest cell distribution among the tissues tested.</p><p><strong>Conclusions: </strong>Quantitative evaluation of qPCR and ddPCR using Alu sequences was conducted, demonstrating that the test method can be adapted for BD evaluation.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512323","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":"Female-to-male allogeneic transplantation affects outcomes differently according to the type of haplo-transplantation.","authors":"Masaharu Tamaki, Shunto Kawamura, Kosuke Takano, Hirohisa Nakamae, Noriko Doki, Hiroyuki Ohigashi, Yumiko Maruyama, Shuichi Ota, Nobuhiro Hiramoto, Tetsuya Eto, Satoshi Yoshihara, Ken-Ichi Matsuoka, Masayoshi Masuko, Makoto Onizuka, Yoshinobu Kanda, Takahiro Fukuda, Yoshiko Atsuta, Ryu Yanagisawa, Kimikazu Yakushijin, Hideki Nakasone","doi":"10.1016/j.jcyt.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.09.007","url":null,"abstract":"<p><p>Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49-0.99], P = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68-1.16], P = 0.40; NRM 0.98 [95% CI: 0.68-1.41], P = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512322","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":"Safety and efficacy of adipose-derived mesenchymal stem cell therapy in elderly Parkinson's disease patients: an intermediate-size expanded access program.","authors":"Ridhima Vij, Hosu Kim, Hyeonggeun Park, Thanh Cheng, Djamchid Lotfi, Donna Chang","doi":"10.1016/j.jcyt.2024.09.004","DOIUrl":"10.1016/j.jcyt.2024.09.004","url":null,"abstract":"<p><strong>Objective: </strong>This intermediate-size expanded access program aimed to evaluate safety and clinical efficacy of multiple intravenous infusions of autologous, Hope Biosciences adipose-derived mesenchymal stem cell (HB-adMSC) therapy in elderly patients with Parkinson's disease (PD).</p><p><strong>Methods: </strong>Ten eligible participants (aged 76-95 years) received six intravenous infusions each with 200MM autologous HB-adMSCs over 18 weeks, with the end of study (EOS) at week 26. Safety was assessed through adverse events (AEs) and serious adverse events (SAEs). Efficacy was measured through improvements in both motor and non-motor symptoms, utilizing scales including Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-IV, Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's disease Fatigue Scale (PFS-16), Patient Health Questionnaire-9 (PHQ-9), and Visual Analog Scale (VAS). Analysis employed paired t-tests and Minimal Clinically Important Difference (MCID) thresholds for the patient-reported outcomes.</p><p><strong>Results: </strong>Most AEs (37 out of 46) were mild in severity, with 5 SAEs reported, none attributed to the drug. No deaths occurred. Despite lack of statistical significance across the efficacy endpoints, modest yet clinically meaningful improvements with effect size > 0.3 were observed in several secondary efficacy endpoints (MDS-UPDRS part I & III, PDQ-39, and PHQ-9) at the EOS, nearing or surpassing the established MCID values.</p><p><strong>Conclusions: </strong>The administration of autologous 200MM HB-adMSCs was found to be safe and well-tolerated in the elderly PD population. Although not achieving statistical significance, modest clinical improvements were noted across multiple secondary endpoints. These findings underscore the safety profile of the treatment in elderly patients and highlight the importance of evaluating clinical relevance alongside statistical measures for meaningful patient outcomes. Further investigation with a larger, randomized, placebo-controlled design is warranted to validate these observations.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479787","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":null,"pages":null},"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}