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Cytotherapy

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https://www.readbyqxmd.com/read/28506444/monocyte-lineage-derived-il-6-does-not-affect-chimeric-antigen-receptor-t-cell-function
#1
Nathan Singh, Ted J Hofmann, Zachary Gershenson, Bruce L Levine, Stephan A Grupp, David T Teachey, David M Barrett
BACKGROUND AIMS: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has demonstrated remarkable success in targeting B-cell malignancies but is often complicated by serious systemic toxicity in the form of cytokine release syndrome (CRS). CRS symptoms are primarily mediated by interleukin 6 (IL-6), and clinical management has focused on inhibition of IL-6 signaling. The cellular source and function of IL-6 in CRS remain unknown. METHODS: Using co-culture assays and data from patients on our clinical CAR T-cell trials, we investigated the cellular source of IL-6, as well as other CRS-associated cytokines, during CAR T-cell activation...
May 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28495397/safety-profile-and-long-term-engraftment-of-human-cd31-blood-progenitors-in-bone-tissue-engineering
#2
Hadar Zigdon-Giladi, Rina Elimelech, Gal Michaeli-Geller, Utai Rudich, Eli E Machtei
BACKGROUND: Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. METHODS: hEPCs were isolated from peripheral blood, cultured and characterized...
May 8, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28483281/preclinical-data-support-leveraging-cs1-chimeric-antigen-receptor-t-cell-therapy-for-systemic-light-chain-amyloidosis
#3
Michael Rosenzweig, Ryan Urak, Miriam Walter, Laura Lim, James F Sanchez, Amrita Krishnan, Stephen Forman, Xiuli Wang
BACKGROUND AIMS: Light chain amyloidosis (AL) is a protein deposition disorder that is a result of a plasma cell dyscrasia, similar to multiple myeloma (MM). Immunotherapy is an attractive approach because of the low burden of disease, but the optimal target for AL is unclear. CS1 and B-cell maturation antigen (BCMA) are two potential targets because they are expressed on normal plasma cells and MM cells. METHODS: We performed a prospective study evaluating bone marrow specimens of 20 patients with plasma cell diseases, 10 with AL and 10 with MM...
May 5, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28479049/co-culture-of-infrapatellar-fat-pad-derived-mesenchymal-stromal-cells-and-articular-chondrocytes-in-plasma-clot-for-cartilage-tissue-engineering
#4
Aditya Arora, M Sriram, Anjaney Kothari, Dhirendra S Katti
BACKGROUND: Cell source plays a deterministic role in defining the outcome of a cell-based cartilage regenerative therapy and its clinical translational ability. Recent efforts in the direction of co-culture of two or more cell types attempt to combine the advantages of constituent cell types and negate their demerits. METHODS: We examined the potential of co-culture of infrapatellar fat pad-derived mesenchymal stromal cells (IFP MSCs) and articular chondrocytes (ACs) in plasma clots in terms of their ratios and culture formats for cartilage tissue engineering...
May 4, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28478920/intravenous-infusion-of-adipose-derived-stem-stromal-cells-improves-functional-recovery-of-rats-with-spinal-cord-injury
#5
Yuki Ohta, Akemi Hamaguchi, Masanori Ootaki, Minoru Watanabe, Yuko Takeba, Taroh Iiri, Naoki Matsumoto, Mitsuko Takenaga
BACKGROUND AIMS: Adipose tissue has therapeutic potential for spinal cord injury (SCI) because it contains multipotent cells known as adipose-derived stem/stromal cells (ASCs). In this study, we attempted intravenous ASC transplantation in rats with SCI to examine the effect on functional recovery. METHODS: ASCs (2.5 × 10(6)) were intravenously infused into SCI rats, after which hindlimb motor function was evaluated. Distribution of transplanted ASCs was investigated and growth factor/cytokine levels were determined...
May 3, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28457740/regulatory-perspective-on-in-vitro-potency-assays-for-human-mesenchymal-stromal-cells-used-in-immunotherapy
#6
REVIEW
Charlotte de Wolf, Marja van de Bovenkamp, Marcel Hoefnagel
Mesenchymal stromal cells (MSCs) are multipotent cells derived from various tissues that can differentiate into several cell types. MSCs are able to modulate the response of immune cells of the innate and adaptive immune system. Because of these multimodal properties, the potential use of MSCs for immunotherapies is currently explored in various clinical indications. Due to the diversity of potential MSC medicinal products at the level of cell source, manufacturing process and indication, distinct functionality tests may be needed to ensure the quality for each of the different products...
April 27, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28457739/mesenchymal-stromal-cells-from-umbilical-cord-wharton-s-jelly-trigger-oligodendroglial-differentiation-in-neural-progenitor-cells-through-cell-to-cell-contact
#7
Byron Oppliger, Marianne S Joerger-Messerli, Cedric Simillion, Martin Mueller, Daniel V Surbek, Andreina Schoeberlein
BACKGROUND AIMS: Wharton's jelly mesenchymal stromal cells (WJ-MSCs) might be ideal candidates to treat perinatal brain damage. Their secretome has been shown to have beneficial effects on neuroregeneration, in part through interaction with neural progenitor cells (NPCs). However, it remains unclear whether cell-to-cell contact decisively contributes to this positive effect. The objective of this study was to elucidate the mechanism through which differentiation in NPCs is triggered after exposure to WJ-MSCs...
April 27, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28454682/the-adipose-tissue-derived-stromal-vascular-fraction-cells-from-lipedema-patients-are-they-different
#8
Eleni Priglinger, Christoph Wurzer, Carolin Steffenhagen, Julia Maier, Victoria Hofer, Anja Peterbauer, Sylvia Nuernberger, Heinz Redl, Susanne Wolbank, Matthias Sandhofer
BACKGROUND AIMS: Lipedema is a hormone-related disease of women characterized by enlargement of the extremities caused by subcutaneous deposition of adipose tissue. In healthy patients application of autologous adipose tissue-derived cells has shown great potential in several clinical studies for engrafting of soft tissue reconstruction in recent decades. The majority of these studies have used the stromal vascular fraction (SVF), a heterogeneous cell population containing adipose-derived stromal/stem cells (ASC), among others...
April 25, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28454681/human-mesenchymal-stem-cells-with-enhanced-telomerase-activity-acquire-resistance-against-oxidative-stress-induced-genomic-damage
#9
Varvara Trachana, Spyros Petrakis, Zisis Fotiadis, Evangelia K Siska, Vasileios Balis, Efstathios S Gonos, Martha Kaloyianni, George Koliakos
BACKGROUND: Human mesenchymal stem cells (MSC) are important tools for several cell-based therapies. However, their use in such therapies requires in vitro expansion during which MSCs quickly reach replicative senescence. Replicative senescence has been linked to macromolecular damage, and especially oxidative stress-induced DNA damage. Recent studies on the other hand, have implicated telomerase in the cellular response to oxidative damage, suggesting that telomerase has a telomere-length independent function that promotes survival...
April 25, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28462822/effects-of-human-umbilical-cord-blood-derived-mesenchymal-stromal-cells-and-dermal-fibroblasts-on-diabetic-wound-healing
#10
Kyung-Chul Moon, Jong-Seok Lee, Seung-Kyu Han, Hyup-Woo Lee, Eun-Sang Dhong
BACKGROUND AIMS: A previous study demonstrated that human umbilical cord blood-derived mesenchymal stromal cells (hUCB-MSCs) have superior wound-healing activity compared with fibroblasts in vitro. However, wound healing in vivo is a complex process that involves multiple factors. The purpose of this study was to compare the effects of hUCB-MSCs and fibroblasts on diabetic wound healing in vivo. This study especially focused on collagen synthesis and angiogenesis, which are considered to be the important factors affecting diabetic wound healing...
April 24, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28462821/aging-of-bone-marrow-and-umbilical-cord-derived-mesenchymal-stromal-cells-during-expansion
#11
Samantha F H de Witte, Eleonora E Lambert, Ana Merino, Tanja Strini, Hannie J C W Douben, Lisa O'Flynn, Steve J Elliman, Annelies J E M M de Klein, Philip N Newsome, Carla C Baan, Martin J Hoogduijn
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are used as experimental immunotherapy. Extensive culture expansion is necessary to obtain clinically relevant cell numbers, although the impact on MSCs stability and function is unclear. This study investigated the effects of long-term in vitro expansion on the stability and function of MSCs. METHODS: Human bone marrow-derived (bmMSCs) and umbilical cord-derived (ucMSCs) MSCs were in vitro expanded. During expansion, their proliferative capacity was examined...
April 24, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28438482/manufacture-and-preparation-of-human-placenta-derived-mesenchymal-stromal-cells-for-local-tissue-delivery
#12
Lee Lankford, Y Julia Chen, Zoe Saenz, Priyadarsini Kumar, Connor Long, Diana Farmer, Aijun Wang
BACKGROUND: In this study we describe the development of a Current Good Manufacturing Practice (CGMP)-compliant process to isolate, expand and bank placenta-derived mesenchymal stromal cells (PMSCs) for use as stem cell therapy. We characterize the viability, proliferation and neuroprotective secretory profile of PMSCs seeded on clinical-grade porcine small intestine submucosa extracellular matrix (SIS-ECM; Cook Biotech). METHODS: PMSCs were isolated from early gestation placenta chorionic villus tissue via explant culture...
April 21, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28434806/fibronectin-adherent-peripheral-blood-derived-mononuclear-cells-as-paclitaxel-carriers-for-glioblastoma-treatment-an-in-vitro-study
#13
Marco Paolo Schiariti, Francesco Restelli, Paolo Ferroli, Anna Benetti, Angiola Berenzi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Moris Cadei, Gaetano Finocchiaro, Augusto Pessina, Eugenio Parati, Roberto Pallini, Giulio Alessandri
BACKGROUND: Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. METHODS: MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients...
April 20, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28433516/intravenous-mesenchymal-stromal-cell-therapy-for-inflammatory-bowel-disease-lessons-from-the-acute-graft-versus-host-disease-experience
#14
REVIEW
Laurie S Conklin, Patrick J Hanley, Jacques Galipeau, John Barrett, Cather M Bollard
Bone marrow-derived mesenchymal stromal cells (BMSCs) are primitive, supportive cells of the bone marrow with tri-lineage potential to differentiate into bone, cartilage, fat and muscle. These cells possess both in vitro and in vivo immunomodulatory and wound-healing properties. Several studies have demonstrated efficacy of intravenously administered BMSCs in treating acute graft-versus-host disease (GvHD). Use of intravenous (IV) BMSCs in inflammatory bowel diseases (IBD) in humans has been limited to small studies in adults, but results have been promising...
April 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28433515/understanding-clinical-development-of-chimeric-antigen-receptor-t-cell-therapies
#15
Sofieke de Wilde, Henk-Jan Guchelaar, Maarten Laurens Zandvliet, Pauline Meij
BACKGROUND AIMS: In the past decade, many clinical trials with gene- and cell-based therapies (GCTs) have been performed. Increased interest in the development of these drug products by various stakeholders has become apparent. Despite this growth in clinical studies, the number of therapies receiving marketing authorization approval (MAA) is lagging behind. To enhance the success rate of GCT development, it is essential to better understand the clinical development of these products...
April 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28433514/cox-2-inhibition-potentiates-mouse-bone-marrow-stem-cell-engraftment-and-differentiation-mediated-wound-repair
#16
Ramasatyaveni Geesala, Neha R Dhoke, Amitava Das
BACKGROUND: Engraftment of transplanted stem cells is often limited by cytokine and noncytokine proinflammatory mediators at the injury site. We examined the role of Cyclooxygenase-2 (Cox-2)-induced cytokine-mediated inflammation on engraftment of transplanted bone marrow stem cells (BMSCs) at the wound site. METHODS: BMSCs isolated from male C57/BL6J mice were transplanted onto excisional splinting wounds in syngenic females in presence or absence of celecoxib, Cox-2 specific inhibitor (50 mg/kg, body weight [b wt]), to evaluate engraftment and wound closure...
April 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28428057/natural-killer-cells-differentiated-in-vitro-from-cord-blood-cd34-cells-are-more-advantageous-for-use-as-an-immunotherapy-than-peripheral-blood-and-cord-blood-natural-killer-cells
#17
Anna Domogala, Michael Blundell, Adrian Thrasher, Mark W Lowdell, J Alejandro Madrigal, Aurore Saudemont
BACKGROUND AIMS: Natural killer (NK) cells have the potential to become a successful immunotherapy as they can target malignant cells without being direct effectors of graft-versus-host disease. Our group has previously shown that large numbers of functional NK cells can be differentiated in vitro from umbilical cord blood (CB) CD34(+) cells. To produce a clinically relevant and effective immunotherapy, we hypothesized that it is essential that the NK cells are able to proliferate and persist in vivo while maintaining an optimal activation status and killing capacity...
April 17, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28411126/low-interleukin-2-concentration-favors-generation-of-early-memory-t-cells-over-effector-phenotypes-during-chimeric-antigen-receptor-t-cell-expansion
#18
Tanja Kaartinen, Annu Luostarinen, Pilvi Maliniemi, Joni Keto, Mikko Arvas, Heini Belt, Jonna Koponen, Angelica Loskog, Satu Mustjoki, Kimmo Porkka, Seppo Ylä-Herttuala, Matti Korhonen
BACKGROUND: Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype...
April 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28395942/ex-vivo-t-cell-depleted-allogeneic-stem-cell-transplantation-for-hematologic-malignancies-the-search-for-an-optimum-transplant-t-cell-dose-and-t-cell-add-back-strategy
#19
Prathima Anandi, Xin Tian, Sawa Ito, Pawel Muranski, Puja D Chokshi, Noelle Watters, Upneet Chawla, Nancy Hensel, David F Stroncek, Minoo Battiwalla, A John Barrett
BACKGROUND: T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10(4)/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10(7)/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT...
April 7, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28392314/persistence-and-proliferation-of-human-mesenchymal-stromal-cells-in-the-right-ventricular-myocardium-after-intracoronary-injection-in-a-large-animal-model-of-pulmonary-hypertension
#20
Roza Badr Eslam, Kevin Croce, Fernanda Marinho Mangione, Robert Musmann, Jane A Leopold, Richard N Mitchell, Aaron B Waxman
BACKGROUND AIMS: In this study, we demonstrate long-term persistence of human mesenchymal stromal cells (hMSCs) after intracoronary injection in a large animal model of pulmonary hypertension (PH). METHODS: Commercially available placenta-derived hMSCs were used. Experiments were conducted on 14 female Yorkshire swine. Four animals served as controls, and 10 underwent pulmonary vein (PV) banding. After 12 ± 2 weeks, PH and PV dysfunction were confirmed by right heart catheterization and cardiac magnetic resonance imaging...
April 6, 2017: Cytotherapy
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