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Stem cells and clinical trials

Anan Huang, Danni Liu, Xin Qi, Zhiwei Yue, Hongmei Cao, Kaiyue Zhang, Xudan Lei, Youzhi Wang, Deling Kong, Jie Gao, Zongjin Li, Na Liu, Yuebing Wang
Mesenchymal stem cell (MSC) transplantation has emerged as a very promising strategy for the treatments of peripheral artery disease (PAD). However, MSC-based therapies are limited by low cell retention and survival rate in the ischemic zone. Small molecular (SM) hydrogels have shown attractive abilities to enhance the therapeutic effects of human MSCs via promoting their proliferation or maintaining their differentiation potential. Here, we designed and synthesized a new bioactive and biocompatible hydrogel, Nap-GFFYK-Thiol, using disulfide bonds as cleavable linkers to control the molecular self-assembly and we hypothesized this hydrogel could enhance the retention and engraftment of human placenta-derived MSCs (hP-MSCs) in a mouse ischemic hindlimb model...
December 11, 2018: Acta Biomaterialia
Sam L Francis, Claudia Di Bella, Gordon G Wallace, Peter F M Choong
There is no long-term treatment strategy for young and active patients with cartilage defects. Early and effective joint preserving treatments in these patients are crucial in preventing the development of osteoarthritis. Tissue engineering over the past few decades has presented hope in overcoming the issues involved with current treatment strategies. Novel advances in 3D bioprinting technology have promoted more focus on efficient delivery of engineered tissue constructs. There have been promising in-vitro studies and several animal studies looking at 3D bioprinting of engineered cartilage tissue...
2018: Frontiers in Surgery
Fabio Morandi, Alberto L Horenstein, Federica Costa, Nicola Giuliani, Vito Pistoia, Fabio Malavasi
Multiple Myeloma (MM) is a hematological cancer characterized by proliferation of malignant plasma cells in the bone marrow (BM). MM represents the second most frequent hematological malignancy, accounting 1% of all cancer and 13% of hematological tumors, with ~9,000 new cases per year. Patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic smoldering MM (SMM) usually evolve to active MM in the presence of increased tumor burden, symptoms and organ damage. Despite the role of high dose chemotherapy in combination with autologous stem cell transplantation and the introduction of new treatments, the prognosis of MM patients is still poor, and novel therapeutic approaches have been tested in the last years, including new immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies (mAbs)...
2018: Frontiers in Immunology
Makoto Yoshimitsu, Atae Utsunomiya, Shigeo Fuji, Hiroshi Fujiwara, Takahiro Fukuda, Hiroyasu Ogawa, Yoshifusa Takatsuka, Kenji Ishitsuka, Akira Yokota, Hirokazu Okumura, Kazuyoshi Ishii, Akinori Nishikawa, Tetsuya Eto, Akihito Yonezawa, Kaname Miyashita, Junichi Tsukada, Junji Tanaka, Yoshiko Atsuta, Koji Kato
Currently, allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative modality for patients with adult T-cell leukemia-lymphoma (ATL). When used in conjunction with posttransplantation cyclophosphamide (PTCY) for graft-versus-host disease prophylaxis, allo-HCT from an HLA haplo-identical donor yields promising outcomes for many diseases other than ATL. However, appropriate comparisons with other donor sources, especially cord blood and conventional HLA haplo-identical donors, are needed to validate the safety and efficacy of this modality...
December 13, 2018: Bone Marrow Transplantation
Valeria Santini
Hypomethylating agents (HMA), azacitidine and decitabine are standard of care for myelodysplastic syndromes. Response to these agents accounts for around 50% of treated patients and duration of response, although variable, is transient. Prediction of response to HMA is possible with clinical and molecular parameters, but alternative approved treatments are not available and in case of HMA failure, there are no standard therapeutic opportunities. It is important to develop a reasoned choice of therapy after HMA failure...
December 13, 2018: Blood
Meletios A Dimopoulos, Francesca Gay, Fredrik Schjesvold, Meral Beksac, Roman Hajek, Katja Christina Weisel, Hartmut Goldschmidt, Vladimir Maisnar, Philippe Moreau, Chang Ki Min, Agnieszka Pluta, Wee-Joo Chng, Martin Kaiser, Sonja Zweegman, Maria-Victoria Mateos, Andrew Spencer, Shinsuke Iida, Gareth Morgan, Kaveri Suryanarayan, Zhaoyang Teng, Tomas Skacel, Antonio Palumbo, Ajeeta B Dash, Neeraj Gupta, Richard Labotka, S Vincent Rajkumar
BACKGROUND: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. METHODS: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America...
December 10, 2018: Lancet
Weijie Xie, Ping Zhou, Yifan Sun, Xiangbao Meng, Ziru Dai, Guibo Sun, Xiaobo Sun
Cerebral ischemia-reperfusion is a complicated pathological process. The injury and cascade reactions caused by cerebral ischemia and reperfusion are characterized by high mortality, high recurrence, and high disability. However, only a limited number of antithrombotic drugs, such as recombinant tissue plasminogen activator (r-TPA), aspirin, and heparin, are currently available for ischemic stroke, and its safety concerns is inevitable which associated with reperfusion injury and hemorrhage. Therefore, it is necessary to further explore and examine some potential neuroprotective agents with treatment for cerebral ischemia and reperfusion injury to reduce safety concerns caused by antithrombotic drugs in ischemic stroke...
December 12, 2018: Cells
Kifayat Ullah, Frank Addai Peprah, Feng Yu, Haifeng Shi
Adoptive cell transfer (ACT) is an emerging immunotherapy technique that restricts tumor growth and invasion in cancer patients. Among the different types of ACT, chimeric antigen receptor (CAR)T‑cell therapy is considered to be the most advanced and a potentially powerful technique for the treatment of cancer in clinical trials. The primary aim of CART‑cell therapy is to destroy cancer cells and therefore, it serves an important role in tumor immunotherapy. CART‑cell therapy has been demonstrated to mainly treat blood cancer by targeting cluster of differentiation (CD)‑19, CD20, CD22, CD33 and CD123...
October 1, 2018: Oncology Reports
Jiadi Gan, Yingjin Wang, Xiaodong Zhou
The efficacy of stem cell (SC) transplantation in patients with type 1 diabetes mellitus (T1DM) has remained to be fully elucidated. In the present study, a systematic review and meta-analysis was performed to determine the clinical outcomes. Electronic databases, including PubMed, MEDLINE, WanFang and the Cochrane Library were screened for relevant studies published until January 13, 2018. The references of retrieved papers, systematic reviews and trial registries were manually screened for additional papers...
December 2018: Experimental and Therapeutic Medicine
Ashley R Paquin, Shaji K Kumar, Francis K Buadi, Morie A Gertz, Martha Q Lacy, Angela Dispenzieri, David Dingli, Lisa Hwa, Amie Fonder, Miriam Hobbs, Suzanne R Hayman, Steven R Zeldenrust, John A Lust, Stephen J Russell, Nelson Leung, Prashant Kapoor, Ronald S Go, Yi Lin, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A Kyle, S Vincent Rajkumar
Overall survival (OS) of multiple myeloma has improved remarkably over time, with the recent Intergroupe Francophone du Myelome (IFM) 2009 randomized trial reporting a 4-year OS rate of approximately 82% in patients receiving modern therapy. However, survival estimates from clinical trials may overestimate outcomes seen in clinical practice even with the adjustment for age and other key characteristics. The purpose of this study was to determine the OS of myeloma patients seen in routine clinical practice who resembled the cohort studied in the IFM 2009 trial...
December 11, 2018: Blood Cancer Journal
John J Moore, Jennifer C Massey, Carole D Ford, Melissa L Khoo, John J Zaunders, Kevin Hendrawan, Yael Barnett, Michael H Barnett, Kain A Kyle, Robert Zivadinov, Kris C Ma, Sam T Milliken, Ian J Sutton, David D F Ma
BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS...
December 11, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Patrick Alan Hagen, Patrick Stiff
Multiple myeloma (MM) is a malignant disorder of plasma cells primarily affecting elderly patients and is the second most commonly diagnosed hematological neoplasm. With the recent influx of effective new agents available including proteasome inhibitors, immunomodulators, targeted monoclonal antibodies, and now chimeric antigen receptor t-cell therapy (CAR-T), the treatment landscape is evolving rapidly. While the role of consolidative autologous stem cell transplantation (ASCT) in first remission is well established, in the relapsed setting following up front ASCT, the role of a second ASCT (SAT) following reinduction is less clear and understudied...
December 8, 2018: Biology of Blood and Marrow Transplantation
Kaveh Baghaei, Samaneh Tokhanbigli, Hamid Asadzadeh, Saeed Nmaki, Mohammad Reza Zali, Seyed Mahmoud Hashemi
Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy...
December 7, 2018: Journal of Cellular Physiology
Siw Johannesen, Bettina Budeus, Sebastian Peters, Sabine Iberl, Anne-Louise Meyer, Tina Kammermaier, Eva Wirkert, Tim-Henrik Bruun, Verena C Samara, Wilhelm Schulte-Mattler, Wolfgang Herr, Armin Schneider, Jochen Grassinger, Ulrich Bogdahn
Objective: To evaluate safety, tolerability and feasibility of long-term treatment with Granulocyte-colony stimulating factor (G-CSF), a well-known hematopoietic stem cell factor, guided by assessment of mobilized bone marrow derived stem cells and cytokines in the serum of patients with amyotrophic lateral sclerosis (ALS) treated on a named patient basis. Methods: 36 ALS patients were treated with subcutaneous injections of G-CSF on a named patient basis and in an outpatient setting. Drug was dosed by individual application schemes (mean 464 Mio IU/month, range 90-2160 Mio IU/month) over a median of 13...
2018: Frontiers in Neurology
Valentina Poletti, Fabrizia Urbinati, Sabine Charrier, Guillaume Corre, Roger P Hollis, Beatriz Campo Fernandez, Samia Martin, Michael Rothe, Axel Schambach, Donald B Kohn, Fulvio Mavilio
Sickle cell disease (SCD) is caused by a mutation (E6V) in the hemoglobin (Hb) β-chain that induces polymerization of Hb tetramers, red blood cell deformation, ischemia, anemia, and multiple organ damage. Gene therapy is a potential alternative to human leukocyte antigen (HLA)-matched allogeneic hematopoietic stem cell transplantation, available to a minority of patients. We developed a lentiviral vector expressing a β-globin carrying three anti-sickling mutations (T87Q, G16D, and E22A) inhibiting axial and lateral contacts in the HbS polymer, under the control of the β-globin promoter and a reduced version of the β-globin locus-control region...
December 14, 2018: Molecular Therapy. Methods & Clinical Development
Attilio Bondanza, Loredana Ruggeri, Maddalena Noviello, Dirk-Jan Eikema, Chiara Bonini, Christian Chabannon, Steffie van der Werf, Anja van Biezen, Liesbeth C de Wreede, Lara Crucitti, Luca Vago, Mara Merluzzi, Maria Speranza Massei, Hendrik Veelken, Yener Koc, Peter Bader, Bernd Gruhn, Franco Locatelli, Fabio Ciceri, Antoine Toubert, Andrea Velardi
HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM)...
December 7, 2018: Bone Marrow Transplantation
Talita Glaser, Vanessa Fernandes Arnaud Sampaio, Claudiana Lameu, Henning Ulrich
Calcium is the ubiquitous second messenger used by any living cell. The fine-tuning of intracellular free calcium [(Ca2+ )i ] homeostasis and signalling pathways is crucial for the maintenance of the healthy organism. Many alterations in the homeostasis can be compensated by robust mechanisms; however, cells that already present some debility in those mechanisms, or that are over stimulated cannot compensate the stress and die. Many neurological diseases show Ca2+ disbalance as trigger of apoptotic response resulting in massive neuronal loss and the neurodegeneration...
December 5, 2018: Seminars in Cell & Developmental Biology
Jiao-Jiao Peng, Rong Sha, Ming-Xing Li, Lu-Ting Chen, Xiao-Hua Han, Feng Guo, Hong Chen, Xiao-Lin Huang
Stem cells hold great promise as a regenerative therapy for ischemic stroke by improving functional outcomes in animal models. However, there are some limitations regarding the cell transplantation, including low rate of survival and differentiation. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in clinical trials as post-stroke rehabilitation in ischemic stroke and has shown to alleviate functional deficits following stroke. The present study was designed to evaluate the therapeutic effects and mechanisms of combined human neural stem cells (hNSCs) with rTMS in a middle cerebral artery occlusion (MCAO) rat model...
December 4, 2018: Experimental Neurology
Afsaneh Amouzegar, Bimalangshu R Dey, Thomas R Spitzer
Although peripheral blood stem cells (PBSC) have worldwide become the predominant source of progenitor cells for hematopoietic stem cell transplantation (HSCT), debate about their role compared with bone marrow (BM) has recently intensified, in large part based on the results of a multicenter Clinical Trials Network study which showed lower incidence of chronic graft-versus-host disease (cGVHD) and improved quality of life in recipients of myeloablative HLA-matched unrelated BM compared with PBSC transplants...
November 12, 2018: Transfusion Medicine Reviews
Ioannis Christodoulou, Maria Goulielmaki, Marina Devetzi, Mihalis Panagiotidis, Georgios Koliakos, Vassilis Zoumpourlis
Mesenchymal stem cells (MSC) comprise a heterogeneous population of rapidly proliferating cells that can be isolated from adult (e.g., bone marrow, adipose tissue) as well as fetal (e.g., umbilical cord) tissues (termed bone marrow (BM)-, adipose tissue (AT)-, and umbilical cord (UC)-MSC, respectively) and are capable of differentiation into a wide range of non-hematopoietic cell types. An additional, unique attribute of MSC is their ability to home to tumor sites and to interact with the local supportive microenvironment which rapidly conceptualized into MSC-based experimental cancer cytotherapy at the turn of the century...
December 7, 2018: Stem Cell Research & Therapy
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