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Richard P Harrison, Ezequiel Zylberberg, Simon Ellison, Bruce L Levine
Cell and gene therapies have demonstrated excellent clinical results across a range of indications with chimeric antigen receptor (CAR)-T cell therapies among the first to reach market. Although these therapies are currently manufactured using patient-derived cells, therapies using healthy donor cells are in development, potentially offering avenues toward process improvement and patient access. An allogeneic model could significantly reduce aggregate cost of goods (COGs), potentially improving market penetration of these life-saving treatments...
February 12, 2019: Cytotherapy
Sandeep Soni, Donald B Kohn
Gene modification of hematopoietic stem cells is increasingly becoming popular as a therapeutic approach, given the recent approvals and the number of new applications for clinical trials targeting monogenetic and immunodeficiency disorders. Technological advances in stem cell selection, culture, transduction and gene editing now allow for efficient ex vivo genetic manipulation of stem cells. Gene-addition techniques using viral vectors (mainly retrovirus- and lentivirus-based) and gene editing using various targeted nuclease platforms (e...
February 8, 2019: Cytotherapy
Komal Kaushik, Amitava Das
BACKGROUND: Neo-vascularization, an indispensible phenomenon for tissue regeneration, facilitates repair and remodeling of wound tissues. This process is impaired in chronic wounds due to reduced number and recruitment of endothelial cells (ECs), thereby necessitating development of newer strategies to enhance the EC repertoire as a therapeutic approach. METHODS: We explored the 'plasticity' of Wharton's jelly derived-mesenchymal stromal cells (WJ-MSCs) using an anti-inflammatory drug-mediated enhanced trans-differentiation into ECs, based on our observation of temporal decrease in COX-2 expression during trans-differentiation of MSCs into ECs at day 7 and 14 along with mature ECs...
February 6, 2019: Cytotherapy
Gabriela Otero, Caroline Agorio, Alexandra Sujanov, Lourdes Echarte, Ana Tchekmedyian, Monica Montelongo, Alba Menyou, Andres Rodriguez, Lilian Diaz, Ismael Rodriguez, Cristina Touriño
BACKGROUND: Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Bone marrow-derived cells (BMDCs) contain cells and secrete cytokines known to participate in wound healing. Thus, BMDC therapy seems a logical strategy for the treatment of chronic wounds...
January 28, 2019: Cytotherapy
Xudong Xie, Hongpei Wu, Mei Li, Xiaojun Chen, Xiaoyun Xu, Wenkai Ni, Cuihua Lu, Runzhou Ni, Baijun Bao, Mingbing Xiao
Cancer is the second leading cause of death in the world with a high annual incidence level. Researchers have been working on developing treatments for cancer. Targeted therapy is an emerging treatment modality that is more novel than surgery, radiotherapy and chemotherapy. In targeted therapy, exogenous nanoscale microparticles are applied as carriers for drugs or genes. However, conventional particles have certain limitations attributed to non-specific cytotoxicity, biocompatibility and low delivery efficacy in individual therapeutic vector systems...
January 24, 2019: Cytotherapy
Claire Roddie, Maeve O'Reilly, Juliana Dias Alves Pinto, Ketki Vispute, Mark Lowdell
Clinical trials of adoptively transferred CD19 chimeric antigen receptor (CAR) T cells have delivered unprecedented responses in patients with relapsed refractory B-cell malignancy. These results have prompted Food and Drug Administration (FDA) approval of two CAR T-cell products in this high-risk patient population. The widening range of indications for CAR T-cell therapy and increasing patient numbers present a significant logistical challenge to manufacturers aiming for reproducible delivery systems for high-quality clinical CAR T-cell products...
January 23, 2019: Cytotherapy
Jieru Cai, Xiaoyan Jiao, Shuan Zhao, Yiran Liang, Yichun Ning, Yiqin Shi, Yi Fang, Xiaoqiang Ding, Xiaofang Yu
BACKGROUND: Regulatory T cells (Tregs) suppress excessive immune responses and play a crucial protective role in acute kidney injury (AKI). The aim of this study was to examine the therapeutic potential of transforming growth factor (TGF)-β1-overexpressing mesenchymal stromal cells (MSCs) in inducing local generation of Tregs in the kidney after ischemia/reperfusion (I/R) injury. METHODS: MSCs were transduced with a lentiviral vector expressing the TGF-β1 gene; TGF-β1-overexpressing MSCs (designated TGF-β1/MSCs) were then transfused into the I/R-injured kidney via the renal artery...
January 23, 2019: Cytotherapy
Briony C Strachan, Hui Xia, Eszter Vörös, Sean C Gifford, Sergey S Shevkoplyas
BACKGROUND: The isolation of lymphocytes - and removal of platelets (PLTs) and red blood cells (RBCs) - from an initial blood sample prior to culture is a key enabling step for effective manufacture of cellular therapies. Unfortunately, currently available methods suffer from various drawbacks, including low cell recovery, need for complex equipment, potential loss of sterility and/or high materials/labor cost. METHODS: A newly developed system for selectively concentrating leukocytes within precisely designed, but readily fabricated, microchannels was compared with conventional density gradient centrifugation with respect to: (i) ability to recover lymphocytes while removing PLTs/RBCs and (ii) growth rate and overall cell yield once expanded in culture...
January 16, 2019: Cytotherapy
Rita Tendeiro Rego, Emma C Morris, Mark W Lowdell
Immunotherapy constitutes an exciting and rapidly evolving field, and the demonstration that genetically modified T-cell receptors (TCRs) can be used to produce T-lymphocyte populations of desired specificity offers new opportunities for antigen-specific T-cell therapy. Overall, TCR-modified T cells have the ability to target a wide variety of self and non-self targets through the normal biology of a T cell. Although major histocompatibility complex (MHC)-restricted and dependent on co-receptors, genetically engineered TCRs still present a number of characteristics that ensure they are an important alternative strategy to chimeric antigen receptors (CARs), and high-affinity TCRs can now be successfully engineered with the potential to enhance therapeutic efficacy while minimizing adverse events...
January 14, 2019: Cytotherapy
Hanne Salmenkari, Anita Laitinen, Richard A Forsgård, Mervi Holappa, Jere Lindén, Lauri Pasanen, Matti Korhonen, Riitta Korpela, Johanna Nystedt
BACKGROUND: Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various pre-clinical and clinical IBD studies is also challenging due to a large variation in study designs. METHODS: In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryopreserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis...
January 2, 2019: Cytotherapy
Zhilong Ma, Guodong Song, Dongbo Zhao, Dalu Liu, Xiaolei Liu, Yuxiang Dai, Zhigang He, Daohai Qian, Jian Gong, Hongbo Meng, B O Zhou, Tingsong Yang, Zhenshun Song
BACKGROUND AND AIMS: It has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1). METHODS: Six hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally...
December 29, 2018: Cytotherapy
Vamsee D Myneni, Ian Mc Clain-Caldwell, Daniel Martin, Lynn Vitale-Cross, Karoly Marko, Joseph M Firriolo, Brian I Labow, Eva Mezey
Bone marrow-derived stromal cells or mesenchymal stromal cells (BMSCs or MSCs, as we will call them in this work) are multipotent progenitor cells that can differentiate into osteoblasts, adipocytes and chondrocytes. In addition, MSCs have been shown to modulate the function of a variety of immune cells. Donor age has been shown to affect the regenerative potential, differentiation, proliferation and anti-inflammatory potency of MSCs; however, the impact of donor age on their immunosuppressive activity is unknown...
December 27, 2018: Cytotherapy
Ilaria Zollino, Diana Campioni, Maria Grazia Sibilla, Mirko Tessari, Anna Maria Malagoni, Paolo Zamboni
BACKGROUND AIMS: Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs). METHODS: From an initial cohort of 38 patients, 16 patients affected by non-healing VLUs were randomly allocated to the experimental arm (5 men and 3 women) and control arm (5 men and 3 women). In the experimental arm, wounds were treated by debridement, centrifuged adipose tissue (CAT), advanced dressings and compression...
December 21, 2018: Cytotherapy
Zheng Xiao, Cheng-Qiong Wang, Ji-Hong Feng, Ming-Hua Zhou, Yu-Zhi Wang, Na-Na Li, Yong-Ping Sun, Shi-Yu Liu, Xin-Sheng Yao, Cheng-Wen Li, Bin Ma, Jie Ding, Ling Chen
BACKGROUND AIMS: Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells improves clinical effectiveness and to reveal its optimal use in non-small cell lung cancer (NSCLC), we systematically reevaluated all relevant studies. METHODS: We collected all studies about chemotherapy with CIK cells for NSCLC from the Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Data, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and U...
December 14, 2018: Cytotherapy
Jacques Galipeau, Daniel J Weiss, Massimo Dominici
No abstract text is available yet for this article.
December 12, 2018: Cytotherapy
Kevin P Robb, Joan C Fitzgerald, Frank Barry, Sowmya Viswanathan
Mesenchymal stromal cell (MSC) therapies have been pursued for a broad spectrum of indications but mixed reports on clinical efficacy have given rise to some degree of skepticism regarding the effectiveness of this approach. However, recent reports of successful clinical outcomes and regulatory approvals for graft-versus-host disease, Crohn's disease and critical limb ischemia have prompted a shift in this perspective. With hundreds of clinical trials involving MSCs currently underway and an increasing demand for large-scale manufacturing protocols, there is a critical need to develop standards that can be applied to processing methods and to establish consensus assays for both MSC processing control and MSC product release...
December 6, 2018: Cytotherapy
Eleni Gounari, Angelos Daniilidis, Nikolaos Tsagias, Anna Michopoulou, Kokkona Kouzi, George Koliakos
BACKGROUND: Recent studies highlight the existence of a population of cord blood (CB)-derived stem cells that bare embryonic features (very small embryonic-like stem cells [VSELs]) as the most primitive CB-stem cell population. In the present study, we present for the first time a novel and high purity isolation method of VSELs with in vitro hematopoietic capacity in the presence of Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs). METHODS: The experimental procedure includes isolation upon gradually increased centrifugation spins and chemotaxis to Stromal cell-derived factor 1a (SDF-1a)...
December 4, 2018: Cytotherapy
Shayesteh Khalifeh Soltani, Bijan Forogh, Naser Ahmadbeigi, Homayoun Hadizadeh Kharazi, Khadijeh Fallahzadeh, Ladan Kashani, Masoumeh Karami, Yadollah Kheyrollah, Mohammad Vasei
OBJECTIVE: Knee osteoarthritis (OA) is a common skeletal impairment that can cause many limitations in normal life activities. Stem cell therapy has been studied for decades for its regenerative potency in various diseases. We investigated the safety and efficacy of intra-articular injection of placental mesenchymal stem cells (MSCs) in knee OA healing. METHODS: In this double-blind, placebo-controlled clinical trial, 20 patients with symptomatic knee OA were randomly divided into two groups to receive intra-articular injection of either 0...
December 3, 2018: Cytotherapy
Gamze Dereli Can, Özge Ekin Akdere, Mehmet Erol Can, Menemşe Gümüşderelioğlu
BACKGROUND: Several methods to cultivate limbal epithelial stem cells (LESCs) in vitro with the support of feeder layers and different growth medium formulations have been established for several years. The initial green medium consists of various ingredients that exhibit a non-optimal level of biosafety, therefore, different modifications have been made to suit it to safe clinical applications. However, the question of which formulation is the most appropriate remains to be answered...
November 30, 2018: Cytotherapy
Emily L Hopewell, Cheryl Cox, Shari Pilon-Thomas, Linda L Kelley
Adoptive cell therapy of tumor-infiltrating lymphocytes has shown promise for treatment of refractory melanoma and other solid malignancies; however, challenges to manufacturing have limited its widespread use. Traditional manufacturing efforts were lengthy, cumbersome and used open culture systems. We describe changes in testing and manufacturing that decreased the process cycle time, enhanced the robustness of critical quality attribute testing and facilitated a functionally closed system. These changes have enabled export of the manufacturing process to support multi-center clinical trials...
November 30, 2018: Cytotherapy
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