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Ex vivo expansion

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https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#1
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, José-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan J Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TIL can be used in adoptive T cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TIL in vivo. In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TIL without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TIL before expansion, only T cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TIL, specifically recognized tumor cells...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28507811/adoptive-natural-killer-cell-therapy-is-effective-in-reducing-pulmonary-metastasis-of-ewing-sarcoma
#2
Alexander A Tong, Hasan Hashem, Saada Eid, Frederick Allen, Daniel Kingsley, Alex Y Huang
The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506845/ex-vivo-mesenchymal-precursor-cell-expanded-cord-blood-transplantation-following-reduced-intensity-conditioning-regimens-improves-time-to-neutrophil-recovery
#3
Rohtesh S Mehta, Rima M Saliba, Kai Cao, Indreshpal Kaur, Katy Rezvani, Julianne Chen, Amanda Olson, Simrit Parmar, Nina Shah, David Marin, Amin Alousi, Chitra Hosing, Uday Popat, Partow Kebriaei, Richard Champlin, Marcos de Lima, Donna Skerrett, Elizabeth Burke, Elizabeth J Shpall, Betul Oran
We previously showed the safety of using cord blood (CB) expanded ex vivo in cocultures with allogeneic mesenchymal precursor cells (MPC) after myeloablative conditioning with faster recovery of neutrophils and platelets compared with historical controls. Herein, we report the transplant outcomes of 27 patients with hematologic cancers who received one CB unit ex vivo expanded with MPCs in addition to an unmanipulated CB (MPC group) after reduced intensity conditioning (RIC). The results in this group were compared with 51 historical controls who received two unmanipulated CB units (control group)...
May 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28498863/notch-ligands-regulate-the-muscle-stem-like-state-ex-vivo-but-are-not-sufficient-for-retaining-regenerative-capacity
#4
Hiroshi Sakai, Sumiaki Fukuda, Miki Nakamura, Akiyoshi Uezumi, Yu-Taro Noguchi, Takahiko Sato, Mitsuhiro Morita, Harumoto Yamada, Kunihiro Tsuchida, Shahragim Tajbakhsh, So-Ichiro Fukada
Myogenic stem cells are a promising avenue for the treatment of muscular disorders. Freshly isolated muscle stem cells have a remarkable engraftment ability in vivo, but their cell number is limited. Current conventional culture conditions do not allow muscle stem cells to expand in vitro with their bona fide engraftment efficiency, requiring the improvement of culture procedures for achieving successful cell-therapy for muscle disorders. Here we expanded mouse muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to activate Notch signaling in vitro and to investigate whether these cells could retain their engraftment efficiency...
2017: PloS One
https://www.readbyqxmd.com/read/28491060/shaping-of-natural-killer-cell-antitumor-activity-by-ex-vivo-cultivation
#5
REVIEW
Markus Granzin, Juliane Wagner, Ulrike Köhl, Adelheid Cerwenka, Volker Huppert, Evelyn Ullrich
Natural killer (NK) cells are a promising tool for the use in adoptive immunotherapy, since they efficiently recognize and kill tumor cells. In this context, ex vivo cultivation is an attractive option to increase NK cells in numbers and to improve their antitumor potential prior to clinical applications. Consequently, various strategies to generate NK cells for adoptive immunotherapy have been developed. Here, we give an overview of different NK cell cultivation approaches and their impact on shaping the NK cell antitumor activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484739/usage-of-human-mesenchymal-stem-cells-in-cell-based-therapy-advantages-and-disadvantages
#6
REVIEW
Hee Jung Kim, Jeong-Soo Park
The use of human mesenchymal stem cells (hMSCs) in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it shows applications to numerous incurable diseases. hMSCs show several superior properties for therapeutic use compared to other types of stem cells. Different cell types are discussed in terms of their advantages and disadvantages, with focus on the characteristics of hMSCs. hMSCs can proliferate readily and produce differentiated cells that can substitute for the targeted affected tissue...
March 2017: Balsaeng'gwa Saengsig
https://www.readbyqxmd.com/read/28480300/toward-a-rapid-production-of-multivirus-specific-t-cells-targeting-bkv-adenovirus-cmv-and-ebv-from-umbilical-cord-blood
#7
Hema Dave, Min Luo, J W Blaney, Shabnum Patel, Cecilia Barese, Conrad Russell Cruz, Elizabeth J Shpall, Catherine M Bollard, Patrick J Hanley
Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28465379/cell-therapy-in-kidney-transplantation-focus-on-regulatory-t-cells
#8
Nicholas A Zwang, Joseph R Leventhal
Renal transplantation is the renal replacement modality of choice for suitable candidates with advanced CKD or ESRD. Prevention of rejection, however, requires treatment with nonspecific pharmacologic immunosuppressants that carry both systemic and nephrologic toxicities. Use of a patient's own suppressive regulatory T cells (Tregs) is an attractive biologic approach to reduce this burden. Here, we review the immunologic underpinnings of Treg therapy and technical challenges to developing successful cell therapy...
May 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28465186/expansion-and-cryopreservation-of-porcine-and-human-corneal-endothelial-cells
#9
Leah A Marquez-Curtis, Locksley E McGann, Janet A W Elliott
Impairment of the corneal endothelium causes blindness that afflicts millions worldwide and constitutes the most often cited indication for corneal transplants. The scarcity of donor corneas has prompted the alternative use of tissue-engineered grafts which requires the ex vivo expansion and cryopreservation of corneal endothelial cells. The aims of this study are to culture and identify the conditions that will yield viable and functional corneal endothelial cells after cryopreservation. Previously, using human umbilical vein endothelial cells (HUVECs), we employed a systematic approach to optimize the post-thaw recovery of cells with high membrane integrity and functionality...
April 29, 2017: Cryobiology
https://www.readbyqxmd.com/read/28460641/the-production-method-affects-the-efficacy-of-platelet-derivatives-to-expand-mesenchymal-stromal-cells-in-vitro
#10
Martina Bernardi, Francesco Agostini, Katia Chieregato, Eliana Amati, Cristina Durante, Mario Rassu, Marco Ruggeri, Sabrina Sella, Elisabetta Lombardi, Mario Mazzucato, Giuseppe Astori
BACKGROUND: The use of fetal bovine serum (FBS) as a media supplement for the ex vivo expansion of bone-marrow derived mesenchymal stromal cells (BM-MSC) has been discouraged by regulatory agencies, due to the risk of transmitting zoonoses and to elicit immune reactions in the host once transplanted. Platelet derivatives are valid FBS substitutes due to their content of growth factors that can be released disrupting the platelets by physical methods or physiological stimuli. We compared platelet derivatives produced by freezing/thawing (platelet lysates, PL) or after CaCl2 activation (platelet releasate surnatant rich in growth factors, PR-SRGF) for their content in growth factors and their ability to support the ex vivo expansion of BM-MSC...
May 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28460313/bf2-azadipyrromethene-nir-emissive-fluorophores-with-research-and-clinical-potential
#11
Harrison C Daly, Gonzalo Sampedro, Corentin Bon, Dan Wu, Ghazi Ismail, Ronan A Cahill, Donal F O'Shea
The use of near-infrared fluorescence for in vivo research and intraoperative clinical imaging is rapidly expanding, with new applications being proposed and developed. While imaging hardware and software have significantly progressed in recent times, the molecular fluorescent agents remain a limiting factor. In this report, the design, synthesis, photophysical characterization and bio-medical imaging assessment of two new NIR-fluorophores based on the BF2-azadipyrromethene fluorophore class are described...
April 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28457196/immunomodulation-in-systemic-lupus-erythematosus-induction-of-m2-population-in-monocyte-derived-macrophages-by-pioglitazone
#12
S Mohammadi, M Saghaeian-Jazi, S Sedighi, A Memarian
Macrophages have recently gained attention in systemic lupus erythematosus (SLE) pathogenesis for their role in the anti-inflammatory clearance of apoptotic cells. The M1/M2 polarization of macrophages improves efferocytic capability. Peroxisome proliferator-activated receptor γ is proposed to function in the expansion of the M2 subpopulation. Pioglitazone is a peroxisome proliferator-activated receptor γ agonist with a variety of anti-inflammatory effects. In this paper, we investigated the ex vivo alterations of monocyte-derived macrophages of 15 newly diagnosed SLE patients and 10 normal subjects triggered by apoptotic cells among SLE patients following pioglitazone treatment...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28451995/a-protocol-to-prepare-decellularized-stem-cell-matrix-for-rejuvenation-of-cell-expansion-and-cartilage-regeneration
#13
Jingting Li, Ming Pei
Traditional ex vivo expansion of adult stem cells yields an insufficient quantity of less potent cells. Here we describe the fabrication of decellularized matrix deposited by synovium-derived stem cells (SDSCs). This matrix could serve as a three-dimensional expansion system to rejuvenate cells for proliferation and tissue-specific differentiation potential, which could benefit cartilage regeneration. The decellularized stem cell matrix (DSCM) might be a powerful system for tissue engineering and regeneration...
April 28, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28446750/expandable-mg-based-helical-stent-assessment-using-static-dynamic-and-porcine-ex-vivo-models
#14
Youngmi Koo, Tarannum Tiasha, Vesselin N Shanov, Yeoheung Yun
A bioresorbable metallic helical stent was explored as a new device opportunity (magnesium scaffold), which can be absorbed by the body without leaving a trace and simultaneously allowing restoration of vasoreactivity with the potential for vessel remodeling. In this study, developed Mg-based helical stent was inserted and expanded in vessels with subsequent degradation in various environments including static, dynamic, and porcine ex vivo models. By assessing stent degradation in three different environments, we observed: (1) stress- and flow-induced degradation; (2) a high degradation rate in the dynamic reactor; (3) production of intermediate products (MgO/Mg(OH)2 and Ca/P) during degradation; and (4) intermediate micro-gas pocket formation in the neighboring tissue ex vivo model...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28438184/microbiota-activated-cd103-dcs-stemming-from-microbiota-adaptation-specifically-drive-%C3%AE-%C3%AE-t17-proliferation-and-activation
#15
Chris Fleming, Yihua Cai, Xuan Sun, Venkatakrishna R Jala, Feng Xue, Samantha Morrissey, Yu-Ling Wei, Yueh-Hsiu Chien, Huang-Ge Zhang, Bodduluri Haribabu, Jian Huang, Jun Yan
BACKGROUND: IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103(+) dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103(+) DCs, and γδT17 cells. METHODS: Immunophenotyping of IL-17r(-/-) mice and IL-17r(-/-) IRF8(-/-) mice were performed by ex vivo immunostaining and flow cytometric analysis...
April 24, 2017: Microbiome
https://www.readbyqxmd.com/read/28429709/t-follicular-helper-and-t-follicular-regulatory-cells-have-different-tcr-specificity
#16
Ana Raquel Maceiras, Silvia Cristina Paiva Almeida, Encarnita Mariotti-Ferrandiz, Wahiba Chaara, Fadi Jebbawi, Adrien Six, Shohei Hori, David Klatzmann, Jose Faro, Luis Graca
Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28426442/amniotic-membrane-use-for-management-of-corneal-limbal-stem-cell-deficiency
#17
Alfonso L Sabater, Victor L Perez
PURPOSE OF REVIEW: The current article reviews the most recent surgical techniques for management of corneal limbal stem cell deficiency (LSCD) using amniotic membrane tissue. RECENT FINDINGS: Early successes with amniotic membrane transplantation (AMT) for the treatment of ocular surface disorders have encouraged clinicians to investigate new applications. The use of AMT as a temporary patch in emergency cases in which LSCD may develop has considerably improved the prognosis of these patients...
April 19, 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28412553/native-and-solubilized-decellularized-extracellular-matrix-a-critical-assessment-of-their-potential-for-improving-the-expansion-of-mesenchymal-stem-cells
#18
REVIEW
Aida Shakouri-Motlagh, Andrea J O'Connor, Shaun P Brennecke, Bill Kalionis, Daniel E Heath
Capturing the promise of mesenchymal stem cell (MSC)-based treatments is currently limited by inefficient production of cells needed for clinical therapies. During conventional ex vivo expansion, a large portion of MSCs lose the properties that make them attractive for use in cell therapies. Decellularized extracellular matrix (dECM) has recently emerged as a promising substrate for the improved expansion of MSCs. MSCs cultured on these surfaces exhibit improved proliferation capacity, maintenance of phenotype, and increased differentiation potential...
April 12, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28410303/personalized-therapy-tumor-antigen-discovery-for-adoptive-cellular-therapy
#19
Cassian Yee, Gregory A Lizee
Adoptive cell therapy using endogenous T cells involves the ex vivo isolation and expansion of antigen-specific T cells from the peripheral blood and is uniquely suited for validating and translating antigen discovery. Endogenous T-cell therapy does not require accessible tumor as a source of infiltrating T cells and is free of regulatory and logistical constraints associated with engineering T cells. Candidate epitope peptides identified through antigen discovery may be rapidly implemented as targets in clinical trials of endogenous T-cell therapy and even incorporated as an "ad hoc" approach to personalized treatment when autologous tumor is available...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28409523/leptin-levels-in-patients-with-systemic-lupus-erythematosus-inversely-correlate-with-regulatory-t-cell-frequency
#20
X Wang, Y Qiao, L Yang, S Song, Y Han, Y Tian, M Ding, H Jin, F Shao, A Liu
Leptin levels X.W., Y.Q. and L.Y. contributed equally to this work. are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity...
January 1, 2017: Lupus
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