-
Validating human induced pluripotent stem cell-specific quality control tests for the release of an intermediate drug product in a Good Manufacturing Practice quality system Cytotherapy (IF 4.5) Pub Date : 2024-04-14 Juan Novoa, Inge Westra, Esther Steeneveld, Natascha Fonseca Neves, Lizanne Daleman, Albert Blanch Asensio, Richard P. Davis, Françoise Carlotti, Christian Freund, Ton Rabelink, Pauline Meij, Brigitte Wieles
-
Safety and potential efficacy of expanded mesenchymal stromal cells of bone marrow and umbilical cord origins in patients with chronic spinal cord injuries: a phase I/II study Cytotherapy (IF 4.5) Pub Date : 2024-04-10 Abdalla Awidi, Abdulrahman Al Shudifat, Nael El Adwan, Mahmoud Alqudah, Fatima Jamali, Fathy Nazer, Halla Sroji, Hady Ahmad, Nahla Al-Quzaa, Hanan Jafar
Spinal cord injury (SCI) affects patients' physical, psychological, and social well-being. Presently, treatment modalities for chronic SCI have restricted clinical effectiveness. Mesenchymal stromal cells (MSCs) demonstrate promise in addressing nervous tissue damage. This single-center, open-label, parallel-group randomized clinical trial aimed to assess the safety and efficacy of intraoperative perilesional
-
Functional single-cell analyses of mesenchymal stromal cell proliferation and differentiation using ALDH-activity and mitochondrial ROS content Cytotherapy (IF 4.5) Pub Date : 2024-04-10 Alice Refeyton, Véronique Labat, Margaux Mombled, Marija Vlaski-Lafarge, Zoran Ivanovic
-
Handling the different requirements for commercial and investigational MNC collections by apheresis Cytotherapy (IF 4.5) Pub Date : 2024-04-07 Aleh Bobr, Timothy Roberts, Scott Koepsell, Shelly M. Williams, Joseph Schwartz
With the success of chimeric antigen receptor T-cell (CAR-T) and similar cellular-based therapies, the demand for collection of autologous mononuclear cells by apheresis (MNC(A)) from blood by apheresis has increased. From an apheresis technical standpoint, the collection of MNC(A) is relatively straightforward, especially when compared with collection of hematopoietic progenitor cells (HPC(A)). Most
-
Optimizing lentiviral vector formulation conditions for efficient ex vivo transduction of primary human T cells in chimeric antigen receptor T-cell manufacturing Cytotherapy (IF 4.5) Pub Date : 2024-04-07 Annu Luostarinen, Anssi Kailaanmäki, Vesa Turkki, Marjut Köylijärvi, Piia Käyhty, Hanna Leinonen, Vita Albers-Skirdenko, Eevi Lipponen, Seppo Ylä-Herttuala, Tanja Kaartinen, Hanna P. Lesch, Tuija Kekarainen
Chimeric antigen receptor (CAR) T-cell products are commonly generated using lentiviral vector (LV) transduction. Optimal final formulation buffer (FFB) supporting LV stability during cryostorage is crucial for cost-effective manufacturing. To identify the ideal LV FFB composition for CAR-T production, primary human T cells were transduced with vesicular stomatitis virus G-protein (VSV-G) -pseudotyped
-
Adipose-derived stromal vascular fraction cells to treat long-term pulmonary sequelae of coronavirus disease 2019: 12-month follow-up Cytotherapy (IF 4.5) Pub Date : 2024-04-04 Michael Carstens, Jessy Trujillo, Yanury Dolmus, Carlos Rivera, Santos Calderwood, Judith Lejarza, Carlos López, Kenneth Bertram
Long coronavirus disease (COVID) is estimated to occur in up to 20% of patients with coronavirus disease 2019 (COVID-19) infections, with many having persistent pulmonary symptoms. Mesenchymal stromal cells (MSCs) have been shown to have powerful immunomodulatory and anti-fibrotic properties. Autologous adipose-derived (AD) stromal vascular fraction (SVF) contains MSC and other healing cell components
-
Interfacing Data Science with Cell Therapy Manufacturing: Where We Are and Where We Need to be Cytotherapy (IF 4.5) Pub Date : 2024-04-04 Bryan Wang, Rui Qi Chen, Jing Li, Krishnendu Roy
Although several cell-based therapies have received FDA approval, and others are showing promising results, scalable, and quality-driven reproducible manufacturing of therapeutic cells at a lower cost remains challenging. Challenges include starting material and patient variability, limited understanding of manufacturing process parameter effects on quality, complex supply chain logistics, and lack
-
Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States Cytotherapy (IF 4.5) Pub Date : 2024-04-01 Laura A. Adang, Joshua L. Bonkowsky, Jaap Jan Boelens, Eric Mallack, Rebecca Ahrens-Nicklas, John A. Bernat, Annette Bley, Barbara Burton, Alejandra Darling, Florian Eichler, Erik Eklund, Lisa Emrick, Maria Escolar, Ali Fatemi, Jamie L. Fraser, Amy Gaviglio, Stephanie Keller, Marc C. Patterson, Paul Orchard, Jennifer Orthmann-Murphy, Jonathan D. Santoro, Ludger Schöls, Caroline Sevin, Isha N. Srivastava
Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the (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
-
Ex-vivo expanded CD34+ cell transplantation alleviates fibrotic liver injury via innate immune modulation in metabolic dysfunction-associated steatohepatitis mice Cytotherapy (IF 4.5) Pub Date : 2024-03-30 Atsutaka Masuda, Toru Nakamura, Hideki Iwamoto, Hiroyuki Suzuki, Takahiko Sakaue, Toshimitsu Tanaka, Yasuko Imamura, Nobuyuki Mori, Hironori Koga, Takumi Kawaguchi
In drug-induced liver injury, vascular endothelial progenitor cells, specifically the CD34 cell fractions, have been found to decrease liver fibrosis and promote regeneration. However, it is unclear whether CD34 cell transplantation has anti-fibrogenic effects on MASH, which has previously been treated effectively with anti-angiogenic therapy. We investigated the efficacy of -expanded CD34 cells in
-
Neutrophil generation from hematopoietic progenitor cells and induced pluripotent stem cells (iPSCs): potential applications Cytotherapy (IF 4.5) Pub Date : 2024-03-30 Abdollah Jafarzadeh, Marzieh Motaghi, Sanand Kumar Patra, Zahra Jafarzadeh, Maryam Nemati, Bhaskar Saha
-
Investigation of biomarkers to predict outcomes in allogeneic hematopoietic stem cell transplantation Cytotherapy (IF 4.5) Pub Date : 2024-03-30 Takayoshi Tachibana, Takuya Miyazaki, Ayako Matsumura, Maki Hagihara, Masatsugu Tanaka, Satoshi Koyama, Eriko Ogusa, Jun Aoki, Yuki Nakajima, Hiroyuki Takahashi, Taisei Suzuki, Yoshimi Ishii, Haruka Teshigawara, Kenji Matsumoto, Mayumi Hatayama, Akihiko Izumi, Katsuya Ikuta, Koji Yamamoto, Heiwa Kanamori, Shin Fujisawa, Hideaki Nakajima
Various biomarkers have been developed and evaluated to predict the prognosis and complications of allogeneic hematopoietic cell transplantation (HCT). Most previous studies conducted on different biomarkers evaluated single effects such as those associated with inflammation, immunology, iron metabolism, and nutrition, and only a few studies have comprehensively analyzed markers. The study aimed to
-
Allogeneic transplantation of bone marrow versus peripheral blood stem cells from HLA-identical sibling donors for hematological malignancies in 6064 adults from 2003 to 2020: different impacts on survival according to time period Cytotherapy (IF 4.5) Pub Date : 2024-03-30 Takaaki Konuma, Kotaro Miyao, Hideki Nakasone, Fumihiko Ouchi, Takahiro Fukuda, Masatsugu Tanaka, Yukiyasu Ozawa, Shuichi Ota, Toshiro Kawakita, Naoyuki Uchida, Masashi Sawa, Yuta Katayama, Nobuhiro Hiramoto, Tetsuya Eto, Tatsuo Ichinohe, Yoshiko Atsuta, Junya Kanda, Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy
Mobilized peripheral blood stem cells (PBSC) have been widely used instead of bone marrow (BM) as the graft source for allogeneic hematopoietic cell transplantation (HCT). Although early studies demonstrated no significant differences in survival between PBSC transplantation (PBSCT) and BM transplantation (BMT) from human leukocyte antigen (HLA)-identical sibling donors to adults with hematological
-
Substrate elasticity does not impact DNA methylation changes during differentiation of pluripotent stem cells Cytotherapy (IF 4.5) Pub Date : 2024-03-30 Mohamed H. Elsafi Mabrouk, Kira Zeevaert, Ann-Christine Henneke, Catharina Maaßen, Wolfgang Wagner
Substrate elasticity may direct cell-fate decisions of stem cells. However, it is largely unclear how matrix stiffness affects the differentiation of induced pluripotent stem cells (iPSCs) and whether this is also reflected by epigenetic modifications. We cultured iPSCs on tissue culture plastic (TCP) and polydimethylsiloxane (PDMS) with different Young's modulus (0.2 kPa, 16 kPa or 64 kPa) to investigate
-
Synthetic biology approaches for enhancing safety and specificity of CAR-T cell therapies for solid cancers Cytotherapy (IF 4.5) Pub Date : 2024-03-30 Grace C. Russell, Yassin Hamzaoui, Daniel Rho, Gaurav Sutrave, Joseph S. Choi, Dara S. Missan, Gabrielle A. Reckard, Michael P. Gustafson, Gloria B. Kim
CAR-T cell therapies have been successful in treating numerous hematologic malignancies as the T cell can be engineered to target a specific antigen associated with the disease. However, translating CAR-T cell therapies for solid cancers is proving more challenging due to the lack of truly tumor-associated antigens and the high risk of off-target toxicities. To combat this, numerous synthetic biology
-
Adipose-derived stem cell modulate tolerogenic dendritic cell-induced T cell regulation is correlated with activation of Notch-NFκB signaling Cytotherapy (IF 4.5) Pub Date : 2024-03-29 Yu-Chi Wang, Rong-Fu Chen, Keng-Fan Liu, Wei-Yu Chen, Chia-Chun Lee, Yur-Ren Kuo
Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise
-
Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil Cytotherapy (IF 4.5) Pub Date : 2024-03-29 Camile Giaretta Sachetti, Augusto Barbosa Jr, Antonio Carlos Campos de Carvalho, Denizar Vianna Araujo, Everton Nunes da Silva
The marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese)
-
Complex association of body mass index and outcomes in patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy Cytotherapy (IF 4.5) Pub Date : 2024-03-29 Hai Cheng, Yingjun Sun, Xiaoxue Zhang, Zihan Chen, Lingyan Shao, Jiaying Liu, Dandan Wang, Yegan Chen, Xue Wang, Wei Chen, Wei Sang, Kunming Qi, Zhenyu Li, Cai Sun, Ming Shi, Jianlin Qiao, Qingyun Wu, Lingyu Zeng, Junnian Zheng, Kailin Xu, Jiang Cao
Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy. We conducted a retrospective study of 111 patients with R/R MM who underwent
-
Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients Cytotherapy (IF 4.5) Pub Date : 2024-03-19 Spyridoula Vasileiou, Manik Kuvalekar, Yovana Velazquez, Ayumi Watanabe, Ann M. Leen, Sarah A. Gilmore
Deficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific
-
Accelerating the development of genetically engineered cellular therapies: a framework for extrapolating data across related products Cytotherapy (IF 4.5) Pub Date : 2024-03-16 Mark D. Stewart, Michael Kalos, Vicki Coutinho, Marc Better, Jonathan Jazayeri, Jennifer Yohrling, Julie Jadlowsky, Miriam Fuchs, Shalini Gidwani, Carsten Goessl, Patrick J. Hanley, Jane Healy, Wen Liu, Brittany A. McKelvey, Laura Pearce, Shari Pilon-Thomas, Hillary S. Andrews, Monica Veldman, Judy Vong, Susan P. Weinbach, Jeff D. Allen
Significant advancements have been made in the field of cellular therapy as anti-cancer treatments, with the approval of chimeric antigen receptor (CAR)-T cell therapies and the development of other genetically engineered cellular therapies. CAR-T cell therapies have demonstrated remarkable clinical outcomes in various hematological malignancies, establishing their potential to change the current cancer
-
Development of a robotic cluster for automated and scalable cell therapy manufacturing Cytotherapy (IF 4.5) Pub Date : 2024-03-15 Alice Melocchi, Brigitte Schmittlein, Alexis L. Jones, Yasmine Ainane, Ali Rizvi, Darius Chan, Elaine Dickey, Kelsey Pool, Kenny Harsono, Dorothy Szymkiewicz, Umberto Scarfogliero, Varun Bhatia, Amlesh Sivanantham, Nadia Kreciglowa, Allison Hunter, Miguel Gomez, Adrian Tanner, Marco Uboldi, Arpit Batish, Joanna Balcerek, Mariella Kutova-Stoilova, Sreenivasan Paruthiyil, Luis A. Acevedo, Rachel Stadnitskiy
The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. We present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing
-
Human embryonic stem cell–derived mesenchymal stromal cells suppress inflammation in mouse models of rheumatoid arthritis and lung fibrosis by regulating T-cell function Cytotherapy (IF 4.5) Pub Date : 2024-03-15 Yan Zhong, Yisheng Zhu, Xiaohao Hu, Lin Zhang, Jiahuan Xu, Qingwen Wang, Jingfeng Liu
Rheumatoid arthritis (RA) is characterized by an overactive immune system, with limited treatment options beyond immunosuppressive drugs or biological response modifiers. Human embryonic stem cell–derived mesenchymal stromal cells (hESC-MSCs) represent a novel alternative, possessing diverse immunomodulatory effects. In this study, we aimed to elucidate the therapeutic effects and underlying mechanisms
-
Protocol improvement and multisite validation of a digital soft agar colony formation assay for tumorigenic transformed cells intermingled in cell therapy products Cytotherapy (IF 4.5) Pub Date : 2024-03-13 Kiyoko Bando, Shinji Kusakawa, Hideki Adachi, Mika Yamamoto, Miki Iwata, Atsushi Kitanaka, Eiichiro Ogimura, Tomoharu Osada, Maya Tamura, Orie Terai, Takeshi Watanabe, Tomomi Yoda, Takafumi Yotsumoto, Kinuko Zaizen, Yoji Sato
The administration of human cell-processed therapeutic products (hCTPs) is associated with a risk of tumorigenesis due to the transformed cellular contaminants. To mitigate this risk, these impurities should be detected using sensitive and validated assays. The digital soft agar colony formation (D-SAC) assay is an ultrasensitive test for detecting tumorigenic transformed cells in hCTPs. : In this
-
Human platelet lysate enhances in vivo activity of CAR-Vδ2 T cells by reducing cellular senescence and apoptosis Cytotherapy (IF 4.5) Pub Date : 2024-03-12 Feiyan Mo, Chiou-Tsun Tsai, Rong Zheng, Chonghui Cheng, Helen E. Heslop, Malcolm K. Brenner, Maksim Mamonkin, Norihiro Watanabe
Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy as the result of their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the longevity of CAR-Vδ2 T cells by modulating manufacturing conditions and selecting an optimal CAR costimulatory
-
Programmed spontaneously beating cardiomyocytes in regenerative cardiology Cytotherapy (IF 4.5) Pub Date : 2024-03-12 Keiko Inouye, Stephanie Yeganyan, Kaelen Kay, Finosh G. Thankam
Stem cells have gained attention as a promising therapeutic approach for damaged myocardium, and there have been efforts to develop a protocol for regenerating cardiomyocytes (CMs). Certain cells have showed a greater aptitude for yielding beating CMs, such as induced pluripotent stem cells, embryonic stem cells, adipose-derived stromal vascular fraction cells and extended pluripotent stem cells. The
-
Filling the gap: the workforce of tomorrow for CGT manufacturing as the sector advances Cytotherapy (IF 4.5) Pub Date : 2024-03-12 Emily Hopewell, Nirupama (Rupa) Pike, Josephine Lembong, Matthew Hewitt, Natalie Fekete
Workforce education and development are key cornerstones in advancing and maturing the Cell & Gene Therapy sector. A skilled worker shortage can significantly impact and delay progress as well as the quality of output for any developer, thereby negatively impacting a patient's access to life-saving treatments. Several roundtable discussions were held at the International Society for Cell & Gene Therapy
-
CAR-T cell expansion platforms yield distinct T cell differentiation states Cytotherapy (IF 4.5) Pub Date : 2024-03-12 Hannah W. Song, Michaela Prochazkova, Lipei Shao, Roshini Traynor, Sarah Underwood, Mary Black, Vicki Fellowes, Rongye Shi, Marie Pouzolles, Hsien-Chao Chou, Adam T. Cheuk, Naomi Taylor, Ping Jin, Robert P. Somerville, David F. Stroncek, Javed Khan, Steven L. Highfill
With investigators looking to expand engineered T cell therapies such as CAR-T to new tumor targets and patient populations, a variety of cell manufacturing platforms have been developed to scale manufacturing capacity using closed and/or automated systems. Such platforms are particularly useful for solid tumor targets, which typically require higher CAR-T cell doses. Although T cell phenotype and
-
Contract development and manufacturing organization selection: critical considerations that can make or break your cell and gene therapy development Cytotherapy (IF 4.5) Pub Date : 2024-03-11 Maryam A. Pasdar, Mitchel M. Sivilotti, Peter S. Jaehn, Benham A. Baghbaderani, John Lee, Bruce L. Levine, William D. Milligan
With the increase in cell and gene therapy (CGT) clinical trials in recent years has come a subsequent increase in the number of contract development and manufacturing organizations (CDMOs). Successful transition from development and early-phase clinical trials to commercialization of a CGT product often depends on selecting the best-suited CDMO. However, many CGT companies are small biotech companies
-
Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up Cytotherapy (IF 4.5) Pub Date : 2024-03-11 Maria Jesús del Cerro Marín, Itziar Garcia Ormazábal, Ana Gimeno-Navarro, María Álvarez-Fuente, Paloma López-Ortego, Alejandro Avila-Alvarez, Luis Arruza Gómez, Cristina González-Menchen, Carlos Labrandero de Lera, María Lozano Balseiro, Laura Moreno Gutiérrez, Gustavo Melen Frajilich, Manuel Ramírez Orellana, Natalia Saldaña García, Antonio Pavón Delgado, Máximo Vento Torres, “PULMESCELL” investigators
Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs)
-
Dual production of human mesenchymal stromal cells and derived extracellular vesicles in a dissolvable microcarrier-based stirred culture system Cytotherapy (IF 4.5) Pub Date : 2024-03-11 Hélder Bandarra-Tavares, Teresa Franchi-Mendes, Cristiana Ulpiano, Sara Morini, Navjot Kaur, Abigail Harris-Becker, Mohan C. Vemuri, Joaquim M.S. Cabral, Ana Fernandes-Platzgummer, Cláudia L. da Silva
Cell therapies based on mesenchymal stromal cells (MSCs) have gained an increasing therapeutic interest in the context of multiple disorders. Nonetheless, this field still faces important challenges, particularly concerning suitable manufacturing platforms. Here, we aimed at establishing a scalable culture system to expand umbilical cord-derived Wharton's jelly MSC (MSC(WJ)) and their derived extracellular
-
Clinical effects of tacrolimus blood concentrations early after allogeneic hematopoietic stem cell transplantation Cytotherapy (IF 4.5) Pub Date : 2024-03-06 Hiroyuki Kubo, Osamu Imataki, Tetsuya Fukumoto, Tomoya Ishida, Yukiko Hamasaki Kubo, Shunsuke Yoshida, Makiko Uemura, Haruyuki Fujita, Norimitsu Kadowaki
Tacrolimus (TAC) plus short-term methotrexate (stMTX) is used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). TAC blood concentrations are frequently adjusted to enhance the graft-versus-leukemia/lymphoma effect or attenuate severe GVHD. Limited information is available on the clinical impact of these adjustments and the optimal
-
Good Manufacturing Practice–compliant human induced pluripotent stem cells: from bench to putative clinical products Cytotherapy (IF 4.5) Pub Date : 2024-03-05 Juan J. Novoa, Inge M. Westra, Esther Steeneveld, Natascha Fonseca Neves, Christiaan H. Arendzen, Bahareh Rajaei, Esmée Grundeken, Mehmet Yildiz, Wouter van der Valk, Alison Salvador, Françoise Carlotti, Pascale F. Dijkers, Heiko Locher, Cathelijne W. van den Berg, Karine I. Raymond, Agnete Kirkeby, Christine L. Mummery, Ton J. Rabelink, Christian Freund, Pauline Meij, Brigitte Wieles
Few human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic and autologous hiPSC-derived products. Our standard research protocol for hiPSCs
-
Clinical grade multiparametric cell sorting and gene-marking of regulatory T cells Cytotherapy (IF 4.5) Pub Date : 2024-03-05 Adaeze Precious Ekwe, Raymond Au, Ping Zhang, Benjamin A. McEnroe, Mei Ling Tan, Alda Saldan, Andrea S. Henden, Cheryl J. Hutchins, Ashleigh Henderson, Kari Mudie, Keri Kerr, Madonna Fuery, Glen A. Kennedy, Geoffrey R. Hill, Siok-Keen Tey
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. We developed a Good Manufacturing Practice (GMP) compliant method based on
-
Effects of mitochondrial transplantation on chronic pressure wound healing in a human patient Cytotherapy (IF 4.5) Pub Date : 2024-03-04 Omer Faruk Taner, Oner Ulger, Simay Ersahin, Nesrin Tan Baser, Onur Genc, Gokhan Burcin Kubat
Wound healing is a multistage process that requires a concerted effort of various cell types. The intricate processes involved in the healing of wounds result in high energy requirements. Furthermore, mitochondria play a crucial role in the healing process because of their involvement in neo angiogenesis, growth factor synthesis, and cell differentiation. It is unclear how mitochondria transplantation
-
Clinical-grade human embryonic stem cell–derived mesenchymal stromal cells ameliorate diabetic retinopathy in db/db mice Cytotherapy (IF 4.5) Pub Date : 2024-03-04 Liyuan Rong, Wumei Wei, Yifan Fang, Yanchen Liu, Tingting Gao, Liu Wang, Jie Hao, Xianliang Gu, Jun Wu, Wei Wu
Mesenchymal stromal cells (MSCs) hold great promise in the treatment of diabetic retinopathy (DR), as evidenced by increasing preclinical and clinical studies. However, the absence of standardized and industrialized clinical-grade donor cells hampers the continued development and large-scale clinical application of MSCs-based therapies for DR. Previously, we have identified a unique population of MSCs
-
From theory to therapy: a bibliometric and visual study of stem cell advancements in age-related macular degeneration Cytotherapy (IF 4.5) Pub Date : 2024-03-02 Weina Liu, Chuanhe Zhang, Fengqi Jiang, Yao Tan, Bo Qin
Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and
-
Alternative target recognition elements for chimeric antigen receptor (CAR) T cells: beyond standard antibody fragments Cytotherapy (IF 4.5) Pub Date : 2024-03-02 Matthew A. Nix, Arun P. Wiita
Chimeric antigen receptor T (CAR-T) cells are a remarkably efficacious, highly promising and rapidly evolving strategy in the field of immuno-oncology. The precision of these targeted cellular therapies is driven by the specificity of the antigen recognition element (the “binder”) encoded in the CAR. This binder redirects these immune effector cells precisely toward a defined antigen on the surface
-
Extended characterization of anti-CD19 CAR T cell products manufactured at the point of care using the CliniMACS Prodigy system: comparison of donor sources and process duration Cytotherapy (IF 4.5) Pub Date : 2024-03-02 Ekaterina Malakhova, Dmitriy Pershin, Elena Kulakovskaya, Viktoria Vedmedskaia, Mariia Fadeeva, Oyuna Lodoeva, Tatiana Sozonova, Yakov Muzalevskii, Alexei Kazachenok, Vladislav Belchikov, Larisa Shelikhova, Olga Molostova, Dmitry Volkov, Michael Maschan
The CliniMACS Prodigy closed system is widely used for the manufacturing of chimeric antigen receptor T cells (CAR-T cells). Our study presents an extensive immunophenotypic and functional characterization and comparison of the properties of anti-CD19 CAR-T cell products obtained during long (11 days) and short (7 days) manufacturing cycles using the CliniMACS Prodigy system, as well as cell products
-
Epigenetic challenges on the horizon of chimeric antigen receptor-T Cytotherapy (IF 4.5) Pub Date : 2024-03-02 Giuditta Benincasa, Maria Grazia Strozziero, Maria Assunta Di Pastena, Clelia Criscuolo, Giusy Cetani, Ugo Trama, Claudio Napoli
-
Droplet digital polymerase chain reaction-based quantitation of therapeutic lentiviral vector copies in transduced hematopoietic stem cells Cytotherapy (IF 4.5) Pub Date : 2024-03-01 Suphanun Phuphanitcharoenkun, Kanit Bhukhai, Phetcharat Phanthong, Somsak Prasongtanakij, Aung Khine Linn, Nareerat Sutjarit, Usanarat Anurathapan, Philippe Leboulch, Emmanuel Payen, Suradej Hongeng, Suparerk Borwornpinyo
Gene therapy using lentiviral vectors (LVs) that harbor a functional β-globin gene provides a curative treatment for hemoglobinopathies including beta-thalassemia and sickle cell disease. Accurate quantification of the vector copy number (VCN) and/or the proportion of transduced cells is critical to evaluate the efficacy of transduction and stability of the transgene during treatment. Moreover, commonly
-
“Protein-resistant vanishing counting bead” phenomenon: a new problem with single-platforms for CD34+ quantification? Cytotherapy (IF 4.5) Pub Date : 2024-02-29 D, a, n, i, e, l, , M, a, z, z, a, , M, a, t, o, s
-
Two novel assays demonstrate persistent daratumumab exposure in a pediatric patient with delayed engraftment following allogeneic hematopoietic stem cell transplantation Cytotherapy (IF 4.5) Pub Date : 2024-02-29 Hannah Major-Monfried, Kinga Hosszu, Devin P. McAvoy, Alexander Vallone, Neerav Shukla, Alfred Gillio, Barbara Spitzer, Andrew L. Kung, Maria Cancio, Kevin Curran, Andromachi Scaradavou, Joseph H. Oved, Richard J. O'Reilly, Jaap Jan Boelens, Andrew C. Harris
Daratumumab, a human IgG monoclonal antibody targeting CD38, is a promising treatment for pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL). We describe a case of delayed engraftment following a mismatched, unrelated donor hematopoietic stem cell transplant (HSCT) in a 14-year-old female with relapsed T-ALL, treated with daratumumab and chemotherapy. By Day
-
Cell and gene therapy investment: evolution and future outlook on investor perspectives Cytotherapy (IF 4.5) Pub Date : 2024-02-28 Maximiliano Kunze-Küllmer, Asthika Goonewardene, Sven Kili, Stefanos Theoharis, Patrick Rivers
To better understand the attitudes and behaviors of investors involved in funding cell and gene therapy (CGT) businesses, the Business Development and Finance) subcommittee of International Society for Cell and Gene Therapy, in collaboration with Truist Securities, conducted a broad survey of the investment community in late 2021. This survey follows a similar study that this group executed in 2018
-
The expanding role of blood and tissue establishments in the development of advanced therapy medicinal products Cytotherapy (IF 4.5) Pub Date : 2024-02-28 Aisling Horan, Shada Warreth, Tor Hervig, Allison Waters
The relationship between blood establishments and advanced cellular therapies is evident in several European countries, with some involved in research and development and/or in manufacturing. The aim of the present study was to understand the advanced therapy medicinal product (ATMP) infrastructural, regulatory and logistic requirements needed for the Irish Blood Transfusion Service to support advanced
-
Ex vivo culture resting time impacts transplantation outcomes of genome-edited human hematopoietic stem and progenitor cells in xenograft mouse models Cytotherapy (IF 4.5) Pub Date : 2024-02-24 Selami Demirci, Muhammad B.N. Khan, Gabriela Hinojosa, Anh Le, Alexis Leonard, Khaled Essawi, Bjorg Gudmundsdottir, Xiong Liu, Jing Zeng, Zaina Inam, Rebecca Chu, Naoya Uchida, Daisuke Araki, Evan London, Henna Butt, Stacy A. Maitland, Daniel E. Bauer, Scot A. Wolfe, Andre Larochelle, John F. Tisdale
resting culture is a standard procedure following genome editing in hematopoietic stem and progenitor cells (HSPCs). However, prolonged culture may critically affect cell viability and stem cell function. We investigated whether varying durations of culture resting times impact the engraftment efficiency of human CD34+ HSPCs edited at the enhancer, a key regulator in the expression of fetal hemoglobin
-
Insights from CTTACC: immune system reset by cellular therapies for chronic illness after trauma, infection, and burn Cytotherapy (IF 4.5) Pub Date : 2024-02-24 Kenneth Bertram, Charles Cox, Hasan Alam, Clifford Lowell, Joseph Cuschieri, Biju Parekkadan, Shibani Pati
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
-
Dendritic cell vaccination strategy for the treatment of acute myeloid leukemia: a systematic review Cytotherapy (IF 4.5) Pub Date : 2024-02-24 Jamal Motallebzadeh Khanmiri, Mohsen Alizadeh, Sina Esmaeili, Zeinab Gholami, Ali Safarzadeh, Mohammad Khani-Eshratabadi, Amir Baghbanzadeh, Nazila Alizadeh, Behzad Baradaran
Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting in an aberrant and unregulated cellular growth. The primary therapeutic modalities for AML include chemotherapy and hematopoietic stem cell transplantation. However, it is important to note that these treatments are accompanied by important
-
Therapeutic potential of CRISPR/CAS9 genome modification in T cell-based immunotherapy of cancer Cytotherapy (IF 4.5) Pub Date : 2024-02-23 Pegah Kavousinia, Mohammad Hossein Ahmadi, Hamid Sadeghian, Mahdi Hosseini Bafghi
-
Prognostic factors in haploidentical transplantation with post-transplant cyclophosphamide for acute myeloid leukemia Cytotherapy (IF 4.5) Pub Date : 2024-02-23 Sho Shibata, Yasuyuki Arai, Tadakazu Kondo, Shohei Mizuno, Satoshi Yamasaki, Takashi Akasaka, Noriko Doki, Shuichi Ota, Yumiko Maruyama, Ken-ichi Matsuoka, Koji Nagafuji, Tetsuya Eto, Takashi Tanaka, Hiroyuki Ohigashi, Hirohisa Nakamae, Makoto Onizuka, Takahiro Fukuda, Yoshiko Atsuta, Masamitsu Yanada
Haploidentical hematopoietic stem cell transplantation (haplo‐HCT) is an appropriate option when an HLA-matched related or unrelated donor is not available. Haplo-HCT using post-transplant cyclophosphamide (PTCy) is being increasingly performed worldwide due to its effective suppression of GVHD and its safety. We conducted a large nationwide cohort study to retrospectively analyze 366 patients with
-
High-dose individualized antithymocyte globulin with therapeutic drug monitoring in high-risk cord blood transplant Cytotherapy (IF 4.5) Pub Date : 2024-02-23 Rick Admiraal, A. Birgitta Versluijs, Alwin D.R. Huitema, Lysette Ebskamp, Amelia Lacna, C.T. (Klaartje) de Kanter, Marc B. Bierings, Jaap Jan Boelens, Caroline A. Lindemans, Stefan Nierkens
Graft-versus-host disease (GvHD) and rejection are main limitations of cord blood transplantation (CBT), more so in patients with severe inflammation or previous rejections. While rigorous T-cell depletion with antithymocyte globulin (ATG) is needed to prevent GvHD and rejection, overexposure to ATG leads to slow T-cell recovery after transplantation, especially in CBT. To evaluate high-dose, upfront
-
-
-
-
-
Impact of lower concentrations of dimethyl sulfoxide on cryopreservation of autologous hematopoietic stem cells: a systematic review and meta-analysis of controlled clinical studies Cytotherapy (IF 4.5) Pub Date : 2024-02-21 Bryenah Bennett, Justine Hanotaux, Ajay Ratan Pasala, Tanvir Hasan, Dhuha Hassan, Risa Shor, David S. Allan, Harinad B. Maganti
Cryopreservation of hematopoietic stem cells (HSCs) is crucial for autologous transplantation, cord blood banking and other special circumstances. Dimethyl sulfoxide (DMSO) is used most commonly for cryopreserving HSC products but can cause infusional toxicities and affect cell viability and engraftment after transplant. A systematic review of controlled studies using lower concentrations of DMSO to
-
Strategic infection prevention after genetically modified hematopoietic stem cell therapies: recommendations from the International Society for Cell & Gene Therapy Stem Cell Engineering Committee Cytotherapy (IF 4.5) Pub Date : 2024-02-20 Tami D. John, Gabriela Maron, Allistair Abraham, Alice Bertaina, Senthil Velan Bhoopalan, Alan Bidgoli, Carmem Bonfim, Zane Coleman, Amy DeZern, Jingjing Li, Chrystal Louis, Joseph Oved, Mara Pavel-Dinu, Duncan Purtill, Annalisa Ruggeri, Athena Russell, Robert Wynn, Jaap Jan Boelens, Susan Prockop, Akshay Sharma
There is lack of guidance for immune monitoring and infection prevention after administration of 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
-
Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma Cytotherapy (IF 4.5) Pub Date : 2024-02-19 Xiangke Xin, Li Lin, Yang Yang, Na Wang, Jue Wang, Jinhuan Xu, Jia Wei, Liang Huang, Miao Zheng, Yi Xiao, Fankai Meng, Yang Cao, Xiaojian Zhu, Yicheng Zhang
The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However
-
Potency assay to predict the anti-inflammatory capacity of a cell therapy product for macrophage-driven diseases: overcoming the challenges of assay development and validation Cytotherapy (IF 4.5) Pub Date : 2024-02-18 Samar Sadeghi, Laura Nimtz, Elke Niebergall-Roth, Alexandra Norrick, Stefan Hägele, Lena Vollmer, Jasmina Esterlechner, Markus H. Frank, Christoph Ganss, Karin Scharffetter-Kochanek, Mark Andreas Kluth
Given the high level of product complexity and limited regulatory guidance, designing and implementing appropriate potency assays is often the most challenging part of establishing a quality control testing matrix for a cell-based medicinal product. Among the most elusive tasks are the selection of suitable read-out parameters, the development of assay designs that most closely model the pathophysiological
-
Secretome of bone marrow mesenchymal stromal cells cultured in a dynamic system induces neuroprotection and modulates microglial responsiveness in an α-synuclein overexpression rat model Cytotherapy (IF 4.5) Pub Date : 2024-02-18 Cláudia Raquel Marques, Jonas Campos, Belém Sampaio-Marques, Filipa Ferreira Antunes, Raquel Medina dos Santos Cunha, Deolinda Silva, Sandra Barata-Antunes, Rui Lima, Ana Fernandes-Platzgummer, Cláudia L. da Silva, Rui Amandi Sousa, António José Salgado
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The etiology of the disease remains largely unknown, but evidence have suggested that the overexpression and aggregation of alpha-synuclein (α-syn) play key roles in the pathogenesis and progression of PD. Mesenchymal stromal cells (MSCs) have been earning attention in this field, mainly due to their paracrine capacity.
-
Comparative transcriptome analysis of bone marrow resident versus culture-expanded mouse mesenchymal stem/stromal cells Cytotherapy (IF 4.5) Pub Date : 2024-02-17 Christopher L. Haga, Cori N. Booker, Jacqueline Strivelli, Siddaraju V. Boregowda, Donald G. Phinney
Mesenchymal stem/stromal cells (MSCs) are defined as culture-expanded populations, and although these cells recapitulate many properties of bone marrow (BM) resident skeletal stem/progenitor cells, few studies have directly compared these populations to evaluate how culture adaptation and expansion impact critical quality attributes. We analyzed by RNA sequencing LinSCA1 MSCs enriched from BM by immunodepletion
-
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) Cytotherapy (IF 4.5) Pub Date : 2024-02-17 Fermin Sanchez-Guijo, Joaquim Vives, Annalisa Ruggeri, Christian Chabannon, Selim Corbacioglu, Harry Dolstra, Dominique Farge, Nico Gagelmann, Claire Horgan, Jurgen Kuball, Benedicte Neven, Tuula Rintala, Vanderson Rocha, Isabel Sanchez-Ortega, John A. Snowden, Jaap Jan Zwaginga, Massimiliano Gnecchi, Anna Sureda
Cell and Gene therapy poses evolving challenges. The current manuscript summarizes the discussions held by European Regional Committee of the International Society for Cell & Gene Therapy (ISCT) and the European Society for Blood and Marrow Transplantation (EBMT) on the current challenges in this field, focusing on the European setting. The manuscript emphasizes the imperative assessment of real-world