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Alann Thaffarell Portilho Souza, Gileade Pereira Freitas, Helena Bacha Lopes, Emanuela Prado Ferraz, Fabiola Singaretti Oliveira, Marcio Mateus Beloti, Adalberto Luiz Rosa
BACKGROUND AIMS: Regenerative medicine strategies based on cell therapy are considered a promising approach to repair bone defects. The aims of this study were to evaluate the effect of subculturing on the osteogenic potential of osteoblasts derived from newborn rat calvaria and the effect of these osteoblasts on bone repair of rat calvaria defects. METHODS: Cells were obtained from 50 newborn rat calvaria, and primary osteoblasts (OB) were compared with first passage (OB-P1) in terms of osteogenic potential by assaying cell proliferation, alkaline phosphatase (ALP) activity, extracellular matrix mineralization and gene expression of the osteoblastic markers RUNX2, ALP, osteocalcin and bone sialoprotein...
September 5, 2018: Cytotherapy
Bing Tan, Weixin Yuan, Jinying Li, Pengjie Yang, Zhen Ge, Jia Liu, Chen Qiu, Xiaolong Zhu, Cong Qiu, Dongmei Lai, Lihe Guo, Liang Wang, Luyang Yu
BACKGROUND AIMS: The chronic inflammation of autoimmune diseases develops repetitive localized destruction or systemic disorders, represented by Hashimoto's thyroiditis (HT) and Systemic lupus erythematosus (SLE) respectively. Currently, there are no efficient ways to treat these autoimmune diseases. Therefore, it is critically important to explore new therapeutic strategies. The aim of this study was to investigate the therapeutic efficacy of human amniotic epithelial cells (hAECs) in murine models of HT and SLE...
August 30, 2018: Cytotherapy
María Dolores López-Lucas, Gisela Pachón-Peña, Ana María García-Hernández, Antonio Parrado, Darío Sánchez-Salinas, David García-Bernal, Maria Del Carmen Algueró, Francisca Iniesta Martinez, Miguel Blanquer, Valentín Cabañas-Perianes, Mar Molina-Molina, Cira Asín-Aguilar, José M Moraleda, Robert Sackstein
BACKGROUND: The regenerative and immunomodulatory properties of human mesenchymal stromal cells (hMSCs) have raised great hope for their use in cell therapy. However, when intravenously infused, hMSCs fail to reach sites of tissue injury. Fucose addition in α(1,3)-linkage to terminal sialyllactosamines on CD44 creates the molecule known as hematopoietic cell E-/L-selectin ligand (HCELL), programming hMSC binding to E-selectin that is expressed on microvascular endothelial cells of bone marrow (BM), skin and at all sites of inflammation...
August 29, 2018: Cytotherapy
Tamra Lysaght, Megan Munsie, Adam Castricum, James H P Hui, Kyoshi Okada, Yoji Sato, Yoshiki Sawa, Cameron Stewart, Lip Kun Tan, Lynn H Y Tan, Shigeki Sugii
We report on a roundtable event hosted in Singapore that sought to identify some of the ethical and regulatory challenges in translating autologous cell-based interventions, particularly those claiming to involve stem cells, into safe and effective therapies and to propose some solutions to encourage responsible innovation with these products. Challenges are identified in the three areas of cell manufacturing and processing, innovative uses of autologous cells in clinical practice and standards of evidence...
August 18, 2018: Cytotherapy
E Brabants, K Heyns, S DE Smet, P Devreker, J Ingels, N DE Cabooter, V Debacker, M Dullaers, J P VAN Meerbeeck, B Vandekerckhove, K Y Vermaelen
BACKGROUND: Many efforts have been devoted to improve the performance of dendritic cell (DC)-based cancer vaccines. Ideally, a DC vaccine should induce robust type 1-polarized T-cell responses and efficiently expand antigen (Ag)-specific cytotoxic T-cells, while being applicable regardless of patient human leukocyte antigen (HLA) type. Production time should be short, while maximally being good manufacturing practice (GMP)-compliant. We developed a method that caters to all of these demands and demonstrated the superiority of the resulting product compared with DCs generated using a well-established "classical" protocol...
August 16, 2018: Cytotherapy
Yuriko Nishiyama-Fujita, A I Kawana-Tachikawa, Toshiaki Ono, Yukie Tanaka, Takafumi Kato, Helen E Heslop, Tomohiro Morio, Satoshi Takahashi
BACKGROUND: Restoration of virus-specific immunity by virus specific T cells (VSTs) offers an attractive alternative to conventional drugs, and can be highly effective in immunocompromised patients, including hematopoietic stem cell transplant (HSCT) recipients. However, conventional VSTs manufacture requires preparation of specialized antigen-presenting cells (APCs), prolonged ex vivo culture in serum-containing medium and antigen re-stimulation with viruses or viral vectors to provide viral antigens for presentation on APCs...
August 16, 2018: Cytotherapy
Linde Woudstra, Elisa Meinster, Laura VAN Haren, Amber M Kay, Marit Koopman, Jeroen A M Belien, Martine C Morrison, Albert C VAN Rossum, Marco N Helder, Lynda J M Juffermans, Hans W M Niessen, Paul A J Krijnen
BACKGROUND AIMS: After a myocardial infarction (MI) atherosclerosis is accelerated leading to destabilization of the atherosclerotic plaque. mesenchymal stromal cells are a promising therapeutic option for atherosclerosis. Previously, we demonstrated a novel stem cell delivery technique, with adipose stem cells coupled to microbubbles (i.e., StemBells) as therapy after MI. In this study, we aim to investigate the effect of StemBell therapy on atherosclerotic plaques in an atherosclerotic mouse model after MI...
August 11, 2018: Cytotherapy
Hanren Dai, Yong Zhou, Chuan Tong, Yelei Guo, Fengxia Shi, Yao Wang, Pingping Shen
Psoriasis is a chronic inflammatory skin disorder mediated by the cells and molecules of both the innate and adaptive immune systems. Autologous cytokine-induced killer (CIK) cell infusion is considered an effective and safe cancer treatment and is licensed for this use in China. Accumulated evidence indicating that CD3+ CD56+ cells are significantly decreased in psoriatic patients prompted us to investigate if the restoration of CD3+ CD56+ cells may be beneficial for psoriatic patients. We designed a clinical trial for psoriasis treatment that involved CIK cell infusion because CIK cells include a large amount of CD3+ CD56+ T cells (NCT01894373 at www...
August 9, 2018: Cytotherapy
Geon-Tae Park, Jae-Rim Heo, Seung U Kim, Kyung-Chul Choi
To confirm the anti-tumor effect of engineered neural stem cells (NSCs) expressing cytosine deaminase (CD) and interferon-β (IFN-β) with prodrug 5-fluorocytosine (FC), K562 chronic myeloid leukemia (CML) cells were co-cultured with the neural stem cell lines HB1.F3.CD and HB1.F3.CD.IFN-β in 5-FC containing media. A significant decrease in the viability of K562 cells was observed by the treatment of the NSC lines, HB1.F3.CD and HB1.F3.CD.IFN-β, compared with the control. A modified trans-well assay showed that engineered human NSCs significantly migrated toward K562 CML cells more than human normal lung cells...
August 2, 2018: Cytotherapy
Mona Navaei-Nigjeh, Milad Moloudizargari, Maryam Baeeri, Mahdi Gholami, Nasrin Lotfibakhshaiesh, Masoud Soleimani, Ebrahim Vasheghani-Farahani, Jafar Ai, Mohammad Abdollahi
BACKGROUND AIMS: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs), widely known as multipotent progenitors, release several cytokines that support cell survival and repair. There are in vitro and in vivo studies reporting the regenerative role of AT-MSCs possibly mediated by their protective effects on functional islet cells as well as their capacity to differentiate into insulin-producing cells (IPCs). METHODS: On such a basis, our goal in the present study was to use three different models including direct and indirect co-cultures and islet-derived conditioned medium (CM) to differentiate AT-MSCs into IPCs and to illuminate the molecular mechanisms of the beneficial impact of AT-MSCs on pancreatic islet functionality...
July 29, 2018: Cytotherapy
Dominique Chabot, Antoine Lewin, Lionel Loubaki, RenÉe Bazin
BACKGROUND: We recently showed that transient warming effects decreased the functional and adhesion properties of mesenchymal stromal cells (MSC) while post-thaw viability remained high. In an attempt to better predict functional impairment of cryopreserved MSC, we further analysed the correlation between viability, immunosuppressive activity and adhesion of cells exposed or not to warming events. METHODS: MSC prepared from six umbilical cords were frozen to -130°C and immediately transferred in a dry ice container or exposed to room temperature for 2 to 10 min (warming events) prior to storage in liquid nitrogen...
August 2018: Cytotherapy
Josée Golay, Simona Martinelli, Rachele Alzani, Sabrina Cribioli, Clara Albanese, Elisa Gotti, Bruna Pasini, Benedetta Mazzanti, Riccardo Saccardi, Alessandro Rambaldi, Martino Introna
BACKGROUND: Cytokine-induced killer cells (CIKs) are an advanced therapeutic medicinal product (ATMP) that has shown therapeutic activity in clinical trials but needs optimization. We developed a novel strategy using CIKs from banked cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb) blinatumomab to treat CD19+ malignancies. METHODS: CB-CIKs were expanded in vitro and fully characterized in comparison with peripheral blood (PB)-derived CIKs...
August 2018: Cytotherapy
Romain Guiho, Kevin Biteau, Giulia Grisendi, Mathias Chatelais, Regis Brion, Julien Taurelle, Sarah Renault, Dominique Heymann, Massimo Dominici, Françoise Redini
BACKGROUND: Osteosarcoma (OS) is the most frequent pediatric malignant bone tumor. OS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, many OS cell lines appear resistant to recombinant human (rh)TRAIL-induced apoptosis...
August 2018: Cytotherapy
Richard J Bodnar, Tianbing Yang, Lora H Rigatti, Fang Liu, Alexander Evdokiou, Sandeep Kathju, Latha Satish
BACKGROUND: Pericytes have been shown to have mesenchymal stromal cell-like properties and play a role in tissue regeneration. The goal of this study was to determine whether the addition of a pericyte sheet to a full-thickness dermal wound would enhance the healing of an acute wound. METHODS: Human muscle-derived pericytes and human dermal fibroblasts were formed into cell sheets, then applied to full-thickness excisional wounds on the dorsum of nu/nu mice. Histology was performed to evaluate epidermal and dermal reformation, inflammation and fibrosis...
August 2018: Cytotherapy
Rebecca M Harman, Megan K He, Sheng Zhang, Gerlinde R VAN DE Walle
BACKGROUND: Impaired cutaneous wound healing is common in humans, and treatments are often ineffective. Based on the significant emotional and economic burden of impaired wound healing, innovative therapies are needed. The potential of mesenchymal stromal cell (MSC)-secreted factors to treat cutaneous wounds is an active area of research that is in need of refinement before effective clinical trials can be initiated. The aims of the present study were to (i) study which MSC-secreted factors stimulate dermal fibroblast (DF) migration in vitro and (ii) evaluate the potential of these factors to promote wound healing in vivo...
August 2018: Cytotherapy
Tzuhua Lin, Jukka Pajarinen, Yusuke Kohno, Masahiro Maruyama, Monica Romero-Lopez, Jhih-Fong Huang, Karthik Nathan, Tahsin N Khan, Zhenyu Yao, Stuart B Goodman
BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation. METHODS: Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activation...
August 2018: Cytotherapy
Abel Trujillo-Ocampo, Hyun-Woo Cho, Amanda C Herrmann, Wilfredo Ruiz-Vazquez, Andrew B Thornton, Hong He, Dan Li, Mariam A Qazilbash, Qing Ma, Steven A Porcelli, Elizabeth J Shpall, Jeffrey Molldrem, Jin S Im
BACKGROUND AIMS: CD1d-restricted invariant natural killer (iNK) T cells are rare regulatory T cells that may contribute to the immune-regulation in allogeneic stem cell transplantation (ASCT). Here, we sought to develop an effective strategy to expand human iNK T cells for use in cell therapy to prevent graft-versus-host disease (GVHD) in ASCT. METHODS: Human iNK T cells were first enriched from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting separation, then co-cultured with dendritic cells in the presence of agonist glycolipids, alpha-galactosylceramide, for 2 weeks...
August 2018: Cytotherapy
Paola A Filomeno, Kyung-Phil Kim, Nara Yoon, Iran Rashedi, Victor Dayan, Rita A Kandel, Xing-Hua Wang, Tania C Felizardo, Elliot Berinstein, Salomeh Jelveh, Andrea Filomeno, Jeffrey A Medin, Peter C Ferguson, Armand Keating
BACKGROUND: Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo. METHODS: Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein)...
August 2018: Cytotherapy
Cong Chen, Yin-Hua Ma, Ya-Ting Zhang, Fan Zhang, Ning Zhou, Xiang Wang, Tao Liu, Yu-Min Li
BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy has recently been reported frequently in the treatment of hepatocellular carcinoma (HCC); however, its efficacy remains controversial. In this study, we aimed to evaluate the clinical efficacy of DC-based immunotherapy on HCC by conducting a systematic review and meta-analysis. METHODS: PubMed, Cochrane Library, Embase and Web of Science were searched to identify clinical trials on DC-based immunotherapy for HCC published up to January 31, 2018...
August 2018: Cytotherapy
Gyungah Kim, Yoon Mi Jin, Yeonsil Yu, Ha Yeong Kim, Sangmee Ahn Jo, Yoon Jeong Park, Yoon Shin Park, Inho Jo
BACKGROUND AND AIMS: Osteoporosis, which is a disease characterized by weakening of the bone, affects a large portion of the senior population. The current therapeutic options for osteoporosis have side effects, and there is no effective treatment for severe osteoporosis. Thus, we urgently need new treatment strategies, such as topical therapies and/or safe and effective stem cell therapies. METHODS: We investigated the therapeutic potential of directly injecting human tonsil-derived mesenchymal stem cells (TMSC) into the right proximal tibias of ovariectomized postmenopausal osteoporosis model mice...
August 2018: Cytotherapy
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