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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 study
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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 due to 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 domain. Specifically
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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
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Filling the Gap: The Workforce of Tomorrow for CGT Manufacturing as the Sector Advances Cytotherapy (IF 4.5) Pub Date : 2024-03-12 E. Hopewell, R. Pike, J. Lembong, M. Hewitt, N. 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
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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
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CDMO selection: critical considerations that can make or break your CGT 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
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Repeated Intravenous Doses Of Human Umbilical Cord-Derived Mesenchymal Stromal Cells For Bronchopulmonary Dysplasia: Results of a Phase 1 Clinical Trial with two-year follow-up Cytotherapy (IF 4.5) Pub Date : 2024-03-11 Maria Jesús del Cerro Marín, Itziar Garcia Ormazabal, 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). Preclinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue (UC)-derived MSCs has not yet been tested in extremely-low-gestational-age newborns (ELGANs). We aimed to test the
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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 (MSC) 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, dissolvable microcarriers were combined with xeno(geneic)-free culture medium to expand umbilical cord-derived Wharton's jelly MSC (MSC(WJ))
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Clinical effects of tacrolimus blood concentrations early after allogeneic hematopoietic stem cell transplantation Cytotherapy (IF 4.5) Pub Date : 2024-03-06 Hiroyuki Kubo MD, Osamu Imataki MD PhD, Tetsuya Fukumoto MD PhD, Tomoya Ishida MD, Yukiko Hamasaki Kubo MD, Shunsuke Yoshida MD, Makiko Uemura MD, Haruyuki Fujita MD PhD, Norimitsu Kadowaki MD PhD
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
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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
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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 McEnroe, Mei Ling Tan, Alda Saldan, Andrea S. Henden, Cheryl 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 pre-clinical 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
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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 multi-stage 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
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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
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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
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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
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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
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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
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Droplet digital PCR-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 β-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
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“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
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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
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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
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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
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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
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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
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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
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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
Today, genome editing technologies like zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) are being used in clinical trials and the treatment of diseases like acquired immunodeficiency syndrome (AIDS) and cancer. CRISPR stands out as one of the most advanced tools for genome editing due to its
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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
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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
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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 impact cell viability and engraftment after transplant. A systematic review of controlled studies using lower concentrations of DMSO to
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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
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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
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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
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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.
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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
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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
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Translational application of human keratinocyte-fibroblast cell sheets for accelerated wound healing in a clinically relevant type 2 diabetic rat model Cytotherapy (IF 4.5) Pub Date : 2024-02-16 Kanokaon Benchaprathanphorn, Pornprom Muangman, Kusuma Chinaroonchai, Nantaporn Namviriyachote, Sumate Ampawong, Wannee Angkhasirisap, Kanchana Kengkoom, Kwanchanok Viravaidya-Pasuwat
Despite advancements in wound care, wound healing remains a challenge, especially in individuals with type 2 diabetes. Cell sheet technology has emerged as an efficient and promising therapy for tissue regeneration and wound repair. Among these, bilayered human keratinocyte-fibroblast cell sheets constructed using temperature-responsive culture surfaces have been shown to mimic a normal tissue-like
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Streamlined measurement of chimeric antigen receptor T-cell concentration, size, viability and two-color phenotyping during manufacturing Cytotherapy (IF 4.5) Pub Date : 2024-02-16 Raymone Pajarillo, Luca Paruzzo, Alberto Carturan, Ositadimma Ugwuanyi, Griffin White, Puneeth Guruprasad, Hatcher J Ballard, Ruchi P Patel, Yunlin Zhang, Yong Gu Lee, Seok Jae Albert Hong, Gregory M. Dittami, Marco Ruella
The successful development of CD19-targeted chimeric antigen receptor (CAR) T-cell therapies has led to an exponential increase in the number of patients recieving treatment and the advancement of novel CAR T products. Therefore, there is a strong need to develop streamlined platforms that allow rapid, cost-effective, and accurate measurement of the key characteristics of CAR T cells during manufacturing
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Proteomics of serum-derived extracellular vesicles are associated with the severity and different clinical profiles of patients with COVID-19: An exploratory secondary analysis Cytotherapy (IF 4.5) Pub Date : 2024-02-15 Adriana F. Paes Leme, Sami Yokoo, Ana Gabriela C. Normando, João Vitor S. Ormonde, Romenia Ramos Domingues, Fernanda F. Cruz, Pedro L. Silva, Bruno S.F. Souza, Claudia C. dos Santos, Hugo Castro-Faria-Neto, Camila Marinelli Martins, Miquéias Lopes-Pacheco, Patricia R.M. Rocco
Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical manifestations with the potential to progress to multiple organ dysfunction in severe cases. Extracellular vesicles (EVs) carry a range of biological cargoes, which may be used as biomarkers of disease state. An exploratory secondary analysis of the SARITA-2 and SARITA-1 datasets (randomized clinical trials on patients
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Impact of early cyclosporine A levels on acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation using in vivo T-cell depletion Cytotherapy (IF 4.5) Pub Date : 2024-02-15 Alexander Nikoloudis, Veronika Buxhofer-Ausch, Christoph Aichinger, Michaela Binder, Petra Hasengruber, Emine Kaynak, Dagmar Wipplinger, Robert Milanov, Irene Strassl, Olga Stiefel, Sigrid Machherndl-Spandl, Andreas Petzer, Ansgar Weltermann, Johannes Clausen
Cyclosporin A (CsA) remains a major component of immunosuppressive regimens applied in allogeneic hematopoietic stem cell transplantation (HSCT). The impact of CsA trough levels during the first weeks after HSCT has not yet been investigated specifically in anti-T-lymphocyte globulin (ATLG)-based HSCT from matched related and unrelated donors. To address this issue, we have retrospectively examined
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Scalable manufacture of therapeutic mesenchymal stromal cell products on customizable microcarriers in vertical wheel bioreactors that improve direct visualization, product harvest, and cost Cytotherapy (IF 4.5) Pub Date : 2024-02-15 Andrew Haskell, Berkley P. White, Robert E. Rogers, Erin Goebel, Megan G. Lopez, Andrew E. Syvyk, Daniela A. de Oliveira, Heather A. Barreda, Joshua Benton, Oscar R. Benavides, Sujata Dalal, EunHye Bae, Yu Zhang, Kristen Maitland, Zivko Nikolov, Fei Liu, Ryang Hwa Lee, Roland Kaunas, Carl A. Gregory
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Source of hematopoietic progenitor cells determines their capacity to generate innate lymphoid cells ex vivo Cytotherapy (IF 4.5) Pub Date : 2024-02-15 Said Z. Omar, Vera van Hoeven, Nienke J.E. Haverkate, Jolien M.R. Van der Meer, Carlijn Voermans, Bianca Blom, Mette D. Hazenberg
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Clinically compliant cryopreservation of differentiated retinal pigment epithelial cells Cytotherapy (IF 4.5) Pub Date : 2024-02-13 Laura Baqué-Vidal, Heather Main, Sandra Petrus-Reurer, Alex R. Lederer, Nefeli-Eirini Beri, Frederik Bär, Hugo Metzger, Cheng Zhao, Paschalis Efstathopoulos, Sarah Saietz, Andreas Wrona, Elham Jaberi, Hanni Willenbrock, Hazel Reilly, Mona Hedenskog, Elisabeth Moussaud-Lamodière, Anders Kvanta, J. Carlos Villaescusa, Gioele La Manno, Fredrik Lanner
Age-related macular degeneration (AMD) is the most common cause of blindness in elderly patients within developed countries, affecting more than 190 million worldwide. In AMD, the retinal pigment epithelial (RPE) cell layer progressively degenerates, resulting in subsequent loss of photoreceptors and ultimately vision. There is currently no cure for AMD, but therapeutic strategies targeting the complement
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Mesothelin antigen density influences anti-mesothelin chimeric antigen receptor T cell cytotoxicity Cytotherapy (IF 4.5) Pub Date : 2024-02-13 Gerard J. Chu, Charles G. Bailey, Rajini Nagarajah, Oliver Liang, Cynthia Metierre, Sharon M. Sagnella, Laura Castelletti, Dannel Yeo, Stephen Adelstein, John E.J. Rasko
Several anti-mesothelin (MSLN) chimeric antigen receptor (CAR) T cells are in phase 1/2 clinical trials to treat solid-organ malignancies. The effect of MSLN antigen density on MSLN CAR cytotoxicity against tumor cells has not been examined previously, nor are there data regarding the effect of agents that increase MSLN antigen density on anti-MSLN CAR T cell efficacy. MSLN antigen density was measured
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Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell–depleted hematopoietic cell transplantation in pediatric and young adult patients Cytotherapy (IF 4.5) Pub Date : 2024-02-12 Madhavi Lakkaraja, Audrey Mauguen, Farid Boulad, Maria I. Cancio, Kevin J. Curran, Andrew C. Harris, Nancy A. Kernan, Elizabeth Klein, Andrew L. Kung, Joseph Oved, Susan Prockop, Andromachi Scaradavou, Barbara Spitzer, Richard J. O'Reilly, Jaap Jan Boelens
Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving
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Modeling the selective growth advantage of genetically variant human pluripotent stem cells to identify opportunities for manufacturing process control Cytotherapy (IF 4.5) Pub Date : 2024-02-11 Catherine Beltran-Rendon, Christopher J. Price, Katie Glen, Adrian Stacey, Ivana Barbaric, Robert J. Thomas
The appearance of genetically variant populations in human pluripotent stem cell (hPSC) cultures represents a concern for research and clinical applications. Genetic variations may alter hPSC differentiation potential or cause phenotype variation in differentiated cells. Further, variants may have properties such as proliferative rate, or response to the culture environment, that differ from wild-type
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A novel multicolor fluorescent spot assay for the functional assessment of chimeric antigen receptor (CAR) T-cell products Cytotherapy (IF 4.5) Pub Date : 2024-02-10 Djordje Atanackovic, Thierry Iraguha, Destiny Omili, Stephanie V. Avila, Xiaoxuan Fan, Mehmet Kocoglu, Etse Gebru, Jillian M. Baker, Nishanthini Dishanthan, Kenneth A. Dietze, Ayooluwakiitan Oluwafemi, Nancy M. Hardy, Jean A. Yared, Kim Hankey, Saurabh Dahiya, Aaron P. Rapoport, Tim Luetkens
Chimeric antigen receptor (CAR) T-cell (CAR-T) therapies have revolutionized the treatment of B-cell lymphomas. Unfortunately, relapses after CD19-targeted CAR-T are relatively common and, therefore, there is a critical need for assays able to assess the function and potency of CAR-T products pre-infusion, which will hopefully help to optimize CAR-T therapies. We developed a novel multicolor fluorescent
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US businesses engaged in direct-to-consumer marketing of perinatal stem cell interventions following the Food and Drug Administration's enforcement discretion era Cytotherapy (IF 4.5) Pub Date : 2024-02-08 Leigh Turner, Jia Chieng Wang, Juan Ramon Martinez, Shemms Najjar, Thevin Rajapaksha Arachchilage, Victoria Sahrai
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US state laws on medical freedom and investigational stem cell procedures: a call to focus on state-based legislation Cytotherapy (IF 4.5) Pub Date : 2024-02-03 Kirstin R.W. Matthews, Samantha J. Lowe, Zubin Master
The premature marketing of investigational stem cell interventions (SCIs) is a growing market in the US. Several US states have passed legislation to permit and promote unproven and experimental SCIs for individuals with terminal or chronic diseases. These SCI medical freedom laws, which are largely based on right-to-try legislation, increase access to experimental SCIs with little to no oversight
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Academic challenges on advanced therapy medicinal products’ development: a regulatory perspective Cytotherapy (IF 4.5) Pub Date : 2024-01-23 Eulalia Olesti, Yoana Nuevo, Mireia Bachiller, Elena Guillen, Juan Bascuas, Sara Varea, Joaquín Saez-Peñataro, Gonzalo Calvo
Advanced therapy medicinal products (ATMPs) are becoming the new kid on the block for the treatment of a variety of indications with promising results. Despite the academic contribution to the basic and clinical research of ATMPs, undertaking a full product development process is extraordinarily challenging and demanding for academic institutions. Meeting regulatory requirements is probably the most
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Extracellular vesicles from adipose mesenchymal stem cells target inflamed lymph nodes in experimental autoimmune encephalomyelitis Cytotherapy (IF 4.5) Pub Date : 2024-01-16 Ermanna Turano, Ilaria Scambi, Roberta Bonafede, Silvia Dusi, Gabriele Angelini, Nicola Lopez, Giulia Marostica, Barbara Rossi, Roberto Furlan, Gabriela Constantin, Raffaella Mariotti, Bruno Bonetti
Background aims Adipose mesenchymal stem cells (ASCs) represent a promising therapeutic approach in inflammatory neurological disorders, including multiple sclerosis (MS). Recent lines of evidence indicate that most biological activities of ASCs are mediated by the delivery of soluble factors enclosed in extracellular vesicles (EVs). Indeed, we have previously demonstrated that small EVs derived from
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Incongruity between T cell receptor recognition of breast cancer hotspot mutations ESR1 Y537S and D538G following exogenous peptide loading versus endogenous antigen processing Cytotherapy (IF 4.5) Pub Date : 2024-01-15 Paul Shafer, Wingchi K. Leung, Mae Woods, Jong Min Choi, Carlos M. Rodriguez-Plata, Arushana Maknojia, Andres Mosquera, Lauren K. Somes, Jarrett Joubert, Anthony Manliguez, Rashi Ranjan, Bryan Burt, Hyun-Sung Lee, Bing Zhang, Suzanne Fuqua, Cliona Rooney, Ann M. Leen, Valentina Hoyos
T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic
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Predictive factors that influence the clinical efficacy of umbilical cord–derived mesenchymal stromal cells in the treatment of type 2 diabetes mellitus Cytotherapy (IF 4.5) Pub Date : 2024-01-13 Yuepeng Wang, Haixu Chen, Yijun Li, Haojie Hao, Jiejie Liu, Yulong Chen, Junhua Meng, Saichun Zhang, Weijun Gu, Zhaohui Lyu, Li Zang, Yiming Mu
Background Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many