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Alessandro Poggi, Massimo Giuliani
The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells' growth and expansion can influence neighboring cells' behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC...
November 8, 2016: Vaccines
Christopher R Nitkin, Tracey L Bonfield
: : Mesenchymal stem cells (MSCs) represent a potentially revolutionary therapy for a wide variety of pediatric diseases, but the optimal cell-based therapeutics for such diversity have not yet been specified. The published clinical trials for pediatric pulmonary, cardiac, orthopedic, endocrine, neurologic, and hematologic diseases provide evidence that MSCs are indeed efficacious, but the significant heterogeneity in therapeutic approaches between studies raises new questions. The purpose of this review is to stimulate new preclinical and clinical trials to investigate these factors...
September 13, 2016: Stem Cells Translational Medicine
Lynn B Williams, Carmon Co, Judith B Koenig, Crystal Tse, Emily Lindsay, Thomas G Koch
Equine mesenchymal stromal cells (MSC) are commonly transported, chilled or frozen, to veterinary clinics. These MSC must remain viable and minimally affected by culture, transport, or injection processes. The safety of two carrier solutions developed for optimal viability and excipient use were evaluated in ponies, with and without allogeneic cord blood-derived (CB) MSC. We hypothesized that neither the carrier solutions nor CB-MSC would elicit measurable changes in clinical, hematological, or biochemical parameters...
2016: Frontiers in Veterinary Science
Sayantan Maji, Irene K Yan, Mansi Parasramka, Swathi Mohankumar, Akiko Matsuda, Tushar Patel
Extracellular vesicles (EVs) are membrane-bound vesicles released from cells into the extracellular environment. There is emerging interest in the use of EVs as potential therapeutic interventions. We sought to evaluate the safety of EVs that may be therapeutically used by performing in vitro toxicological assessments. EVs were obtained from mesenchymal stem cells (MSC-EV) or from bovine milk (BM-EV) by differential ultracentrifugation, and quantitated using nanoparticle tracking analysis. Genotoxic effects, hematological effects, immunological effects and endotoxin production were evaluated at two dose levels...
March 2017: Journal of Applied Toxicology: JAT
Ronaldo José Farias Corrêa do Amaral, Nemias Pereira da Silva, Natália Ferreira Haddad, Luana Siqueira Lopes, Fábio Dias Ferreira, Ricardo Bastos Filho, Paola Alejandra Cappelletti, Wallace de Mello, Eric Cordeiro-Spinetti, Alex Balduino
There are promising results in the use of platelet-rich plasma (PRP) for musculoskeletal tissue repair. However, the variability in the methodology for its obtaining may cause different and opposing findings in the literature. Particularly, the choice of the anticoagulant is the first definition to be made. In this work, blood was collected with sodium citrate (SC), ethylenediaminetetraacetic acid (EDTA), or anticoagulant citrate dextrose (ACD) solution A, as anticoagulants, prior to PRP obtaining. Hematological analysis and growth factors release quantification were performed, and the effects on mesenchymal stromal cell (MSC) culture, such as cytotoxicity and cell proliferation (evaluated by MTT method) and gene expression, were evaluated...
2016: Stem Cells International
Seung Ah Choi, Jun-Won Yun, Kyeung Min Joo, Ji Yeoun Lee, Pil Ae Kwak, Young Eun Lee, Ji-Ran You, Euna Kwon, Woo Ho Kim, Kyu-Chang Wang, Ji Hoon Phi, Byeong-Cheol Kang, Seung-Ki Kim
Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1...
June 15, 2016: Stem Cells and Development
Ewa Ferensztajn-Rochowiak, Janusz K Rybakowski
Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s...
April 2016: Pharmacological Reports: PR
Gabrielis Kundrotas, Evelina Gasperskaja, Grazina Slapsyte, Zivile Gudleviciene, Jan Krasko, Ausra Stumbryte, Regina Liudkeviciene
Human bone marrow mesenchymal stem cells (hBM-MSCs) hold promise for treating incurable diseases and repairing of damaged tissues. However, hBM-MSCs face the disadvantages of painful invasive isolation and limited cell numbers. In this study we assessed characteristics of MSCs isolated from residual human bone marrow transplantation material and expanded to clinically relevant numbers at passages 3-4 and 6-7. Results indicated that early passage hBM-MSCs are genomically stable and retain identity and high proliferation capacity...
March 8, 2016: Oncotarget
Li Sun, Rongman Xu, Xiaoxian Sun, Yuping Duan, Yiwen Han, Yuanyuan Zhao, Hui Qian, Wei Zhu, Wenrong Xu
BACKGROUND AIMS: Mounting evidence shows that non-cell-based transplantation of exosomes derived from mesenchymal stromal cells (MSCs) has more potential protective and reparative effects than MSCs have. However, whether it is safe to transplant MSC exosomes into tissues is still not clear. In this study, we evaluated the safety of transplantation of exosomes derived from human umbilical cord MSCs (hucMSC exosomes). METHODS: hucMSC exosomes were incubated with the cardiac blood from a healthy rabbit, and hemolysis was observed...
March 2016: Cytotherapy
Merete Kallekleiv, Lillebeth Larun, Øystein Bruserud, Kimberley Joanne Hatfield
BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for patients with hematological malignancies. Co-transplantation of multipotent mesenchymal stromal cells (MSCs) during allogeneic HSCT has been explored to enhance engraftment and decrease the risk of graft-versus-host disease (GVHD). We aimed to identify, evaluate and summarize the findings of all relevant controlled clinical studies to determine the potential benefits of MSC infusion during allogeneic HSCT, with regard to the outcomes engraftment, GVHD, post-transplant relapse and survival...
February 2016: Cytotherapy
Yasuo Miura
Human mesenchymal stromal/stem cells (MSCs) have capabilities for multi-differentiation, immunomodulation, and hematopoietic support. Based on these unique biological characteristics, human MSCs have been extensively used as a transplantable resource for cell therapy in regenerative medicine, immune diseases, and hematological diseases. One of the most promising therapeutic effects of human MSCs is in hematopoietic stem cell transplantation for acute graft-versus-host disease (GVHD). Off-the-shelf MSC products are approved by regulatory agencies in some countries...
February 2016: International Journal of Hematology
Ivan Martin, Hilary Ireland, Helen Baldomero, Massimo Dominici, Daniël B Saris, Jakob Passweg
Following the coordinated efforts of five established scientific organizations, this report, the sixth of its kind, describes activity in Europe for the year 2013 in the area of cellular and engineered tissue therapies, excluding hematopoietic stem cell (HSC) treatments for the reconstitution of hematopoiesis. Three hundred eighteen teams from 31 countries responded to the cellular and engineered tissue therapy survey; 145 teams from 25 countries reported treating 2187 patients, while a further 173 teams reported no activity...
January 2016: Tissue Engineering. Part A
Xiao-Ting Zhang, Lian-Ning Duan, Li Ding, Ling Zhu, Hong-Min Yan, Zhi-Dong Wang, Sheng Wang, Xiao-Li Zheng, Lei Dong, Mei Xue, Jing Liu, Heng-Xiang Wang
OBJECTIVE: To explore the safety and efficiency of unrelated donor peripheral blood stem cells (URD-PBSC) transplantation combined with umbilical cord mesenchymal stem cells (UC-MSC). METHODS: The clinical data of 49 patients received unrelated donor peripheral blood stem cells transplantation (URD-PBSCT) for treating hematologic malignancies were retrospectively evaluated, including 12 ANLL, 17 ALL, 18 CML and 2 MDS. Out of them, 22 patients received the URD-PBSCT combined with UC-MSC and 27 patients received only URD-PBSCT...
October 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
Tiziana Squillaro, Gianfranco Peluso, Umberto Galderisi
In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs, can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes...
2016: Cell Transplantation
R Aliperta, M Cartellieri, A Feldmann, C Arndt, S Koristka, I Michalk, M von Bonin, A Ehninger, J Bachmann, G Ehninger, M Bornhäuser, M P Bachmann
Bispecific antibodies (bsAbs) engaging T cells are emerging as a promising immunotherapeutic tool for the treatment of hematologic malignancies. Because their low molecular mass, bsAbs have short half-lives. To achieve clinical responses, they have to be infused into patients continously, for a long period of time. As a valid alternative we examined the use of mesenchymal stromal cells (MSCs) as autonomous cellular machines for the constant production of a recently described, fully humanized anti-CD33-anti-CD3 bsAb, which is capable of redirecting human T cells against CD33-expressing leukemic cells...
2015: Blood Cancer Journal
Mohsen Emadedin, Maede Ghorbani Liastani, Roghayeh Fazeli, Fatemeh Mohseni, Reza Moghadasali, Soura Mardpour, Seyyedeh Esmat Hosseini, Maryam Niknejadi, Fatemeh Moeininia, Aslan Aghahossein Fanni, Reza Baghban Eslaminejhad, Ahmad Vosough Dizaji, Narges Labibzadeh, Ali Mirazimi Bafghi, Hossein Baharvand, Nasser Aghdami
BACKGROUND: Osteoarthritis (OA) is a debilitating disease that typically affects a large number of the middle-aged and elderly population. Current treatment strategies have had limited success in these patients. This study aims to investigate the safety of treatment with autologous bone marrow (BM)-derived mesenchymal stem cells (MSCs) transplanted in patients with OA of the knee, ankle, or hip. METHODS: We enrolled 18 patients with different joint involvements (knee, ankle, or hip OA) and one was lost to follow-up...
June 2015: Archives of Iranian Medicine
Joseph P McGuirk, J Robert Smith, Clint L Divine, Micheal Zuniga, Mark L Weiss
Allogeneic hematopoietic cell transplantation (allo-HCT), a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD). The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton's jelly (WJ)-derived mesenchymal stromal cells (MSCs) as a potentially safe and effective therapeutic strategy in the management of GVHD...
2015: Pharmaceuticals
Ivan Martin, Hilary Ireland, Helen Baldomero, Jakob Passweg
Following the coordinated efforts of five established scientific organizations, this report describes activity in Europe for the year 2012 in the area of cellular and engineered tissue therapies, excluding hematopoietic stem cell (HSC) treatments for the reconstitution of hematopoiesis. Three hundred thirteen teams from 33 countries responded to the cellular and engineered tissue therapy survey: 138 teams from 27 countries provided data on 2157 patients, while a further 175 teams reported no activity. Indications were musculoskeletal/rheumatological disorders (36%; 80% autologous), cardiovascular disorders (25%; 95% autologous), hematology/oncology, predominantly prevention or treatment of graft versus host disease and HSC graft enhancement (19%; 1% autologous), neurological disorders (3%; 99% autologous), gastrointestinal disorders (1%; 71% autologous), and other indications (16%; 79% autologous)...
January 2015: Tissue Engineering. Part A
Elena Jones, Richard Schäfer
We describe the current knowledge of the surface marker phenotype of native bone marrow mesenchymal stem/stromal cells (MSCs) in humans and in mouse models, highlighting similarities in the MSC marker "signature" between the two species. The chapter proceeds to discuss the published literature pertaining to native MSC topography and their interactions with hematopoietic stem cells and their progeny, as well as with blood vessels and nerve endings. Additionally, the chapter describes phenotypic and functional "drifts" that occur in MSC preparations as they are taken out of their native bone marrow microenvironment and induced to proliferate in vitro (in the presence of animal or human serum)...
2015: Methods in Molecular Biology
Seon Young Kim, Kyongok Im, Si Nae Park, Jiseok Kwon, Jung-Ah Kim, Qute Choi, Sang Mee Hwang, Sung-Hee Han, Sunghoon Kwon, Il-Hoan Oh, Dong Soon Lee
Cytogenetic testing is important to ensure patient safety before therapeutic application of mesenchymal stromal cells (MSCs). However, the standardized methods and criteria for the screening of chromosomal abnormalities of MSCs have not yet been determined. We investigated the frequency of cytogenetic aberrations in MSCs using G-banding and fluorescence in situ hybridization (FISH) and suggest reference values for aneuploidy in MSCs. Cytogenetic analysis was performed on 103 consecutive cultures from 68 MSCs (25 adipose-origin, 20 bone marrow-origin, 18 cord blood-origin, and 5 neural stem cells; 8 from adipose tissue of patients with breast cancer and 60 from healthy donors)...
January 1, 2015: Stem Cells and Development
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