2,153 results match your criteria Cytotherapy[Journal]


Manufacturing and characterization of extracellular vesicles from umbilical cord-derived mesenchymal stromal cells for clinical testing.

Cytotherapy 2019 Apr 9. Epub 2019 Apr 9.

GMP Laboratory, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Salzburg, Austria; Department of Transfusion Medicine, Paracelsus Medical University (PMU), Salzburg, Austria; Research Program Nanovesicular Therapies, Paracelsus Medical University (PMU), Salzburg, Austria; Celericon Therapeutics G.m.b.H., Paracelsus Medical University (PMU), Salzburg, Austria.

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) may deliver therapeutic effects that are comparable to their parental cells. MSC-EVs are promising agents for the treatment of a variety of diseases. To reach the intermediate goal of clinically testing safety and efficacy of EVs, strategies should strive for efficient translation of current EV research. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.12.006DOI Listing

Sub-confluent culture of human mesenchymal stromal cells on biodegradable polycaprolactone microcarriers enhances bone healing of rat calvarial defect.

Cytotherapy 2019 Apr 8. Epub 2019 Apr 8.

Stem Cell Group 2 Bioprocessing Technology Institute, Agency of Science, Technology and Research (A*STAR), Singapore.

In the current emerging trend of using human mesenchymal stromal cell (MSCs) for cell therapy, large quantities of cells are needed for clinical testing. Current methods of culturing cells, using tissue culture flasks or cell multilayer vessels, are proving to be ineffective in terms of cost, space and manpower. Therefore, alternatives such as large-scale industrialized production of MSCs in stirred tank bioreactors using microcarriers (MCs) are needed. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.03.004DOI Listing
April 2019
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Optimization of manufacturing conditions for chimeric antigen receptor T cells to favor cells with a central memory phenotype.

Cytotherapy 2019 Apr 8. Epub 2019 Apr 8.

Translational Oncology Laboratory, Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia; Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia; School of Medicine, the University of Adelaide, Adelaide, South Australia, Australia.

Background: Chimeric antigen receptor (CAR)-T cells are genetically engineered to recognize tumor-associated antigens and have potent cytolytic activity against tumors. Adoptive therapy with CAR-T cells has been highly successful in B-cell leukemia and lymphoma. However, in solid tumor settings, CAR-T cells face a particularly hostile tumor microenvironment where multiple immune suppressive factors serve to thwart the anti-cancer immune response. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.03.003DOI Listing
April 2019
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Spheroid glioblastoma culture conditions as antigen source for dendritic cell-based immunotherapy: spheroid proteins are survival-relevant targets but can impair immunogenic interferon γ production.

Cytotherapy 2019 Apr 8. Epub 2019 Apr 8.

Activartis Biotech GmbH, Vienna, Austria.

Background: Glioblastoma is the most aggressive type of brain cancer. Dendritic cell (DC)-based immunotherapy against glioblastoma depends on the effectiveness of loaded antigens. Sphere-inducing culture conditions are being studied by many as a potential antigen source. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.03.002DOI Listing

Insulin-like growth factor 2 regulates the proliferation and differentiation of rat adipose-derived stromal cells via IGF-1R and IR.

Cytotherapy 2019 Apr 5. Epub 2019 Apr 5.

Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014 China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014 China; Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Background: Insulin-like growth factor 2 (IGF2), an essential component of the stem cell niche, has been reported to modulate the proliferation and differentiation of stem cells. Previously, a continuous expression of IGF2 in tissues was reported to maintain the self-renewal ability of several types of stem cells. Therefore, in this study, we investigated the expression of IGF2 in adipose tissues and explored the effects of IGF2 on adipose-derived stromal cells (ADSCs) in vitro. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.010DOI Listing

Critical testing and parameters for consideration when manufacturing and evaluating tumor-associated antigen-specific T cells.

Cytotherapy 2019 Mar 28;21(3):278-288. Epub 2019 Mar 28.

Program for Cell Enhancement and Technologies for Immunotherapy, Center for Cancer and Immunology Research; Center for Cancer and Blood Disorders, and the Division of Blood and Marrow Transplantation; Children's National Health System and The George Washington University, Washington, DC, USA. Electronic address:

The past year has seen remarkable translation of cellular and gene therapies, with U.S. Food and Drug Administration (FDA) approval of three chimeric antigen receptor (CAR) T-cell products, multiple gene therapy products, and the initiation of countless other pivotal clinical trials. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.004DOI Listing
March 2019
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Insights into animal models for cell-based therapies in translational studies of lung diseases: Is the horse with naturally occurring asthma the right choice?

Cytotherapy 2019 Mar 29. Epub 2019 Mar 29.

Equine Medicine Unit, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Milano, Italy.

Human asthma is a widespread disease associated with chronic inflammation of the airways, leading to loss of quality of life, disability and death. Corticosteroid administration is the mainstream treatment for asthmatic patients. Corticosteroids reduce airway obstruction and improve quality of life, although symptoms persist despite treatment in many patients. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.010DOI Listing
March 2019
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Translation of a standardized manufacturing protocol for mesenchymal stromal cells: A systematic comparison of validation and manufacturing data.

Cytotherapy 2019 Mar 26. Epub 2019 Mar 26.

Institute for Transfusion Medicine, University Hospital Ulm, Ulm, Germany; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Donation Service Baden-Württemberg - Hessia, Ulm, Germany.

Background: Many data are available on expansion protocols for mesenchymal stromal cells (MSCs) for both experimental settings and manufacturing for clinical trials. However, there is a lack of information on translation of established protocols for Good Manufacturing Practice (GMP) from validation to manufacturing for clinical application. We present the validation and translation of a standardized pre-clinical protocol for isolation and expansion of MSCs for a clinical trial for reconstitution of alveolar bone. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.03.001DOI Listing

Therapeutic efficacy of adipose-derived stromal vascular fraction cells is associated with CD34 positivity in acute-on-chronic liver failure.

Cytotherapy 2019 Mar 25. Epub 2019 Mar 25.

Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Surgery, E-Da Hospital, I-Shou University, Taiwan.

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http://dx.doi.org/10.1016/j.jcyt.2019.02.012DOI Listing
March 2019
1 Read

Characterization of human natural killer cells for therapeutic use.

Cytotherapy 2019 Mar 23;21(3):315-326. Epub 2019 Mar 23.

Department of Haematology, Cancer Institute, University College London, London, UK. Electronic address:

As a part of the innate immune system, natural killer (NK) cells are cytotoxic lymphocytes that can exert cytotoxic activity against infected or transformed cells. Furthermore, due to their expression of a functional Fc receptor, they have also been eluded as a major effector fraction in antibody-dependent cellular cytotoxicity. These characteristics have led to multiple efforts to use them for adoptive immunotherapy against various malignancies. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.001DOI Listing

Improvement of in vitro potency assays by a resting step for clinical-grade chimeric antigen receptor engineered T cells.

Cytotherapy 2019 Mar 23. Epub 2019 Mar 23.

Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany. Electronic address:

Background: Chimeric antigen receptor engineered T (CAR-T) cell therapy is a promising approach currently revolutionizing the field of cancer immunotherapy. However, data concerning clinical-grade CAR-T cell stability and functionality after months of cryopreservation have not been released by companies so far. To investigate the effect of cryopreservation on CAR-T cells and to further optimize the potency assays, we performed this study. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.013DOI Listing
March 2019
2 Reads

Administration of endothelial progenitor cells accelerates the resolution of arterial thrombus in mice.

Cytotherapy 2019 Mar 20. Epub 2019 Mar 20.

Structural and Functional Biology Department, State University of Campinas (UNICAMP), São Paulo, Brazil. Electronic address:

Background: Endothelial progenitor cells (EPCs) are circulating progenitor cells that can play an essential role in vascular remodelling. In this work, we compared the role of two EPCs cultivated with different mediums in the resolution of the arterial thrombus induced by FeCl lesion and in vessel re-endothelization in the mouse carotid artery.

Methods: Mice mononuclear cells were differentiated into EPCs using Dulbecco's Modified Eagle's Medium (DMEM) and vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and IGF (Insulin Growth Factor) called EPCs--M1) or with EGM2(endothelial growth medium) (media supplemented with growth factors from Lonza called (EPCs-M2) for 30days and characterized using flow cytometry. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.01.005DOI Listing

Adipose-derived mesenchymal stromal cells improve hemodynamic function in pulmonary arterial hypertension: identification of microRNAs implicated in modulating endothelial function.

Cytotherapy 2019 Mar 20. Epub 2019 Mar 20.

Department of Respiratory and Critical Care Medicine, Affiliated hospital of Nantong University, Nantong, Jiangsu, China; Medical School of Nantong University, Nantong, Jiangsu, China. Electronic address:

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial endothelial hyperproliferation and dysfunction. Restoration of endothelial function is a common goal of available treatments. In the present study, human adipose-derived mesenchymal stromal cells (ASCs) were co-cultured with monocrotaline pyrrole-treated human pulmonary arterial endothelial cells (HPAECs); increased proliferation of HPAECs and expression of vascular endothelial growth factor (VEGF) were observed. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.011DOI Listing
March 2019
1 Read
3.293 Impact Factor

Proposal for the International Society for Cell & Gene Therapy position statement on assays for the quality control and potency assessment of adoptive cellular immunotherapies.

Cytotherapy 2019 Mar 16. Epub 2019 Mar 16.

Centre for Cell, Gene & Tissue Therapeutics, Royal Free Hospital, London, UK; Department of Haematology, Cancer Institute, University College London, London, UK. Electronic address:

Translation of cell and gene therapies from pre-clinical experiments to clinical trials and final drug licensing brings requires the development, verification and even validation of the assays essential for the definition of the drug product. The technical and scientific challenges in doing this are far greater than they seem at first and are compounded by a lack of approved standards for assays used to support (c)GMP manufacture. This paper highlights some of those challenges and proposes solutions based on the experience of our colleagues using similar assay platforms in regulated pathology laboratories. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.001DOI Listing

Manufacturing of human Wharton's jelly stem cells for clinical use: selection of serum is important.

Cytotherapy 2019 Mar 15. Epub 2019 Mar 15.

Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore. Electronic address:

Background: Human Wharton's jelly-derived mesenchymal stromal cells (hWJSCs) have gained considerable attention for their use in cell therapy. Many of these applications would require manufacturing of millions of hWJSCs. It is, therefore, necessary to develop a Good Manufacturing Practice (GMP)-compliant hWJSC expansion protocol, allowing the generation of a large quantity of cells to meet both clinical and regulatory requirements. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.008DOI Listing

Enrichment of vascular endothelial growth factor secreting mesenchymal stromal cells enhances therapeutic angiogenesis in a mouse model of hind limb ischemia.

Cytotherapy 2019 Mar 14. Epub 2019 Mar 14.

Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seoul, South Korea; Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Critical limb ischemia, a severe manifestation of peripheral artery disease, is emerging as a major concern in aging societies worldwide. Notably, cell-based gene therapy to induce angiogenesis in ischemic tissue has been investigated as treatment. Despite many studies demonstrating the efficacy of this approach, better therapies are required to prevent serious sequelae such as claudication, amputation and other cardiovascular events. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.12.007DOI Listing
March 2019
3 Reads

In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials.

Cytotherapy 2019 Mar 14. Epub 2019 Mar 14.

RHEACELL GmbH & Co. KG, Heidelberg, Germany; TICEBA GmbH, Heidelberg, Germany. Electronic address:

Background Aims: Human dermal ABCB5-expressing mesenchymal stromal cells (ABCB5 MSCs) represent a promising candidate for stem cell-based therapy of various currently uncurable diseases in several fields of regenerative medicine. We have developed and validated a method to isolate, from human skin samples, and expand ABCB5 MSCs that meet the guideline criteria of the International Society for Cellular Therapy. We are able to process these cells into a Good Manufacturing Practice-conforming, MSC-based advanced-therapy medicinal product. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.12.005DOI Listing
March 2019
1 Read

Hypoxia/hypercapnia prevents iron-dependent cold injuries in cord blood stem and progenitor cells.

Cytotherapy 2019 Mar 13. Epub 2019 Mar 13.

Etablissement Français du Sang Nouvelle-Aquitaine, Bordeaux, France; Institut national de la santé et de la recherche médicale, University of Bordeaux, France. Electronic address:

Background: Cold-induced cell injuries are associated with an increase in the cellular labile iron pool (LIP) followed by lipid peroxidation and alteration of mitochondrial function, which lead to cell death. Recently, we showed that incubation in a hypoxic/hypercapnic (HH) gas mixture improved the survival of a population of cord blood hematopoietic progenitors and CD34 hematopoietic progenitor and stem cells in severe hypothermia. To explain the underlying mechanism, here we test if this HH-induced cytoprotection in cold conditions is associated with the level of LIP and lysosome stability. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.006DOI Listing
March 2019
1 Read

Intrathecal cell therapy with autologous stromal cells increases cerebral glucose metabolism and can offer a new approach to the treatment of Alzheimer's type dementia.

Cytotherapy 2019 Mar 14. Epub 2019 Mar 14.

Department of Experimental Psychology, Faculty of Psychology, Complutense University, Madrid, Spain.

Background Aims: After recent observations that intrathecal administration of autologous bone marrow mesenchymal stromal cells (MSCs) increases cerebral metabolism in patients with severe traumatic brain injury (TBI), we examined this type of cell therapy in Alzheimer's type dementia.

Methods: Three patients with clinical diagnosis of Alzheimer's disease received every 3 months 100 million autologous MSCs by intrathecal route, until a total dose of 300 million.

Results: During cell therapy the patients showed arrest in neurological deterioration and two of them manifested clear improvement of previous symptoms. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.009DOI Listing
March 2019
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Pleiotropic roles of autophagy in stem cell-based therapies.

Cytotherapy 2019 Mar 12. Epub 2019 Mar 12.

Department of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery and Anesthesiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Stem cells (SCs) have been proven to possess regenerative and immunomodulatory properties and can be used to treat diseases that involve loss of cells due to tissue damage or inflammation. For this approach to succeed, SCs or their derivatives should be able to engraft in the target tissue at least for a short period of time. Unfortunately, once injected, therapeutic SCs will encounter a hostile environment, including hypoxia, lack of nutrients and stromal support, and cells may also be targeted and rejected by the immune system. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.007DOI Listing

Recent progress on developing exogenous monocyte/macrophage-based therapies for inflammatory and degenerative diseases.

Cytotherapy 2019 Mar 12. Epub 2019 Mar 12.

Arthritis Program, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Cell Therapy Program, University Health Network, Toronto, Ontario, Canada; Division of Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Cell-based therapies are a rapidly developing area of regenerative medicine as dynamic treatments that execute therapeutic functions multimodally. Monocytes and macrophages, as innate immune cells that control inflammation and tissue repair, are increasing popular clinical candidates due to their spectrum of functionality. In this article, we review the role of monocytes and macrophages specifically in inflammatory and degenerative disease pathology and the evidence supporting the use of these cells as an effective therapeutic strategy. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.02.002DOI Listing
March 2019
1 Read

Advancing cellular therapies towards standard of care: a focus on testing of cellular therapy products.

Cytotherapy 2019 Mar 7;21(3):275-277. Epub 2019 Mar 7.

Immuno-Gene Therapy Scientific Committee, International Society for Cell and Gene Therapy, Vancouver, Canada; Department of Haematology, Cancer Institute, University College London, London, UK; Centre for Cell, Gene & Tissue Therapeutics, Royal Free Hospital, London, UK.

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https://linkinghub.elsevier.com/retrieve/pii/S14653249193000
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http://dx.doi.org/10.1016/j.jcyt.2019.02.003DOI Listing
March 2019
6 Reads

Chimeric antigen receptor-T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods.

Cytotherapy 2019 Feb 13;21(2):224-233. Epub 2019 Feb 13.

Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine, and the Abramson Cancer Center, at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Cell and gene therapies have demonstrated excellent clinical results across a range of indications with chimeric antigen receptor (CAR)-T cell therapies among the first to reach market. Although these therapies are currently manufactured using patient-derived cells, therapies using healthy donor cells are in development, potentially offering avenues toward process improvement and patient access. An allogeneic model could significantly reduce aggregate cost of goods (COGs), potentially improving market penetration of these life-saving treatments. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S14653249193000
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http://dx.doi.org/10.1016/j.jcyt.2019.01.003DOI Listing
February 2019
2 Reads

Chemistry, manufacturing and controls for gene modified hematopoietic stem cells.

Cytotherapy 2019 Mar 8;21(3):358-366. Epub 2019 Feb 8.

Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.

Gene modification of hematopoietic stem cells is increasingly becoming popular as a therapeutic approach, given the recent approvals and the number of new applications for clinical trials targeting monogenetic and immunodeficiency disorders. Technological advances in stem cell selection, culture, transduction and gene editing now allow for efficient ex vivo genetic manipulation of stem cells. Gene-addition techniques using viral vectors (mainly retrovirus- and lentivirus-based) and gene editing using various targeted nuclease platforms (e. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.12.001DOI Listing
March 2019
4 Reads

Cycloxygenase-2 inhibition potentiates trans-differentiation of Wharton's jelly-mesenchymal stromal cells into endothelial cells: Transplantation enhances neovascularization-mediated wound repair.

Cytotherapy 2019 Feb 7;21(2):260-273. Epub 2019 Feb 7.

Department of Applied Biology, Council of Scientific and Industrial Research(CSIR), Indian Institute of Chemical Technology, Hyderabad, TS, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address:

Background: Neo-vascularization, an indispensible phenomenon for tissue regeneration, facilitates repair and remodeling of wound tissues. This process is impaired in chronic wounds due to reduced number and recruitment of endothelial cells (ECs), thereby necessitating development of newer strategies to enhance the EC repertoire as a therapeutic approach.

Methods: We explored the 'plasticity' of Wharton's jelly derived-mesenchymal stromal cells (WJ-MSCs) using an anti-inflammatory drug-mediated enhanced trans-differentiation into ECs, based on our observation of temporal decrease in COX-2 expression during trans-differentiation of MSCs into ECs at day 7 and 14 along with mature ECs. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.01.004DOI Listing
February 2019
2 Reads

Autologous bone marrow-derived cells for venous leg ulcers treatment: a pilot study.

Cytotherapy 2019 Feb 28;21(2):189-199. Epub 2019 Jan 28.

Cell Therapy and Regenerative Medicine Unit Medicine Department, Hospital de Clínicas Dr Manuel Quintela, Faculty of Medicine, Universidad de la República, Uruguay. Electronic address:

Background: Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.01.002DOI Listing
February 2019

Progress in the application of exosomes as therapeutic vectors in tumor-targeted therapy.

Cytotherapy 2019 Jan 24. Epub 2019 Jan 24.

Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China. Electronic address:

Cancer is the second leading cause of death in the world with a high annual incidence level. Researchers have been working on developing treatments for cancer. Targeted therapy is an emerging treatment modality that is more novel than surgery, radiotherapy and chemotherapy. Read More

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http://dx.doi.org/10.1016/j.jcyt.2019.01.001DOI Listing
January 2019

Manufacturing chimeric antigen receptor T cells: issues and challenges.

Cytotherapy 2019 Mar 23;21(3):327-340. Epub 2019 Jan 23.

Research Department of Haematology, University College London, London, UK.

Clinical trials of adoptively transferred CD19 chimeric antigen receptor (CAR) T cells have delivered unprecedented responses in patients with relapsed refractory B-cell malignancy. These results have prompted Food and Drug Administration (FDA) approval of two CAR T-cell products in this high-risk patient population. The widening range of indications for CAR T-cell therapy and increasing patient numbers present a significant logistical challenge to manufacturers aiming for reproducible delivery systems for high-quality clinical CAR T-cell products. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.009DOI Listing
March 2019
11 Reads

Transforming growth factor-β1-overexpressing mesenchymal stromal cells induced local tolerance in rat renal ischemia/reperfusion injury.

Cytotherapy 2019 Jan 23. Epub 2019 Jan 23.

Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China. Electronic address:

Background: Regulatory T cells (Tregs) suppress excessive immune responses and play a crucial protective role in acute kidney injury (AKI). The aim of this study was to examine the therapeutic potential of transforming growth factor (TGF)-β1-overexpressing mesenchymal stromal cells (MSCs) in inducing local generation of Tregs in the kidney after ischemia/reperfusion (I/R) injury.

Methods: MSCs were transduced with a lentiviral vector expressing the TGF-β1 gene; TGF-β1-overexpressing MSCs (designated TGF-β1/MSCs) were then transfused into the I/R-injured kidney via the renal artery. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.12.003DOI Listing
January 2019
2 Reads

Improved expansion of T cells in culture when isolated with an equipment-free, high-throughput, flow-through microfluidic module versus traditional density gradient centrifugation.

Cytotherapy 2019 Feb 16;21(2):234-245. Epub 2019 Jan 16.

Department of Biomedical Engineering, University of Houston, Houston, Texas, USA. Electronic address:

Background: The isolation of lymphocytes - and removal of platelets (PLTs) and red blood cells (RBCs) - from an initial blood sample prior to culture is a key enabling step for effective manufacture of cellular therapies. Unfortunately, currently available methods suffer from various drawbacks, including low cell recovery, need for complex equipment, potential loss of sterility and/or high materials/labor cost.

Methods: A newly developed system for selectively concentrating leukocytes within precisely designed, but readily fabricated, microchannels was compared with conventional density gradient centrifugation with respect to: (i) ability to recover lymphocytes while removing PLTs/RBCs and (ii) growth rate and overall cell yield once expanded in culture. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435405PMC
February 2019
2 Reads

T-cell receptor gene-modified cells: past promises, present methodologies and future challenges.

Cytotherapy 2019 Mar 14;21(3):341-357. Epub 2019 Jan 14.

UCL Cancer Institute, Department of Haematology, London, UK.

Immunotherapy constitutes an exciting and rapidly evolving field, and the demonstration that genetically modified T-cell receptors (TCRs) can be used to produce T-lymphocyte populations of desired specificity offers new opportunities for antigen-specific T-cell therapy. Overall, TCR-modified T cells have the ability to target a wide variety of self and non-self targets through the normal biology of a T cell. Although major histocompatibility complex (MHC)-restricted and dependent on co-receptors, genetically engineered TCRs still present a number of characteristics that ensure they are an important alternative strategy to chimeric antigen receptors (CARs), and high-affinity TCRs can now be successfully engineered with the potential to enhance therapeutic efficacy while minimizing adverse events. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.12.002DOI Listing
March 2019
3 Reads

The use of unlicensed bone marrow-derived platelet lysate-expanded mesenchymal stromal cells in colitis: a pre-clinical study.

Cytotherapy 2019 Feb 2;21(2):175-188. Epub 2019 Jan 2.

Advanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland. Electronic address:

Background: Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various pre-clinical and clinical IBD studies is also challenging due to a large variation in study designs.

Methods: In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryopreserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.011DOI Listing
February 2019
5 Reads

Bone marrow-derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1-mediated anti-oxidant and anti-inflammatory effects.

Cytotherapy 2019 Feb 29;21(2):162-174. Epub 2018 Dec 29.

Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

Background And Aims: It has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1).

Methods: Six hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.013DOI Listing
February 2019
2 Reads

Mesenchymal stromal cells from infants with simple polydactyly modulate immune responses more efficiently than adult mesenchymal stromal cells.

Cytotherapy 2019 Feb 27;21(2):148-161. Epub 2018 Dec 27.

Adult Stem Cell Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA. Electronic address:

Bone marrow-derived stromal cells or mesenchymal stromal cells (BMSCs or MSCs, as we will call them in this work) are multipotent progenitor cells that can differentiate into osteoblasts, adipocytes and chondrocytes. In addition, MSCs have been shown to modulate the function of a variety of immune cells. Donor age has been shown to affect the regenerative potential, differentiation, proliferation and anti-inflammatory potency of MSCs; however, the impact of donor age on their immunosuppressive activity is unknown. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S14653249183069
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http://dx.doi.org/10.1016/j.jcyt.2018.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435420PMC
February 2019
2 Reads

A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells.

Cytotherapy 2019 Feb 22;21(2):200-211. Epub 2018 Dec 22.

Department of Morphology, Surgery and Experimental Medicine, Section of Translational of Medicine and Surgery, University of Ferrara, Ferrara, Italy; Sant'Anna University Hospital, Unit of Translational Surgery and Vascular Diseases Center, Ferrara, Italy.

Background Aims: Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs).

Methods: From an initial cohort of 38 patients, 16 patients affected by non-healing VLUs were randomly allocated to the experimental arm (5 men and 3 women) and control arm (5 men and 3 women). In the experimental arm, wounds were treated by debridement, centrifuged adipose tissue (CAT), advanced dressings and compression. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.012DOI Listing
February 2019
3 Reads

Effectiveness and safety of chemotherapy with cytokine-induced killer cells in non-small cell lung cancer: A systematic review and meta-analysis of 32 randomized controlled trials.

Cytotherapy 2019 Feb 14;21(2):125-147. Epub 2018 Dec 14.

Evidence-Based Medicine Center, MOE Virtual Research Center of Evidence-based Medicine at Zunyi Medical College, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China; Department of Respiratory Medicine (Center for Evidence-Based and Translational Medicine of major infectious diseases), Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Background Aims: Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells improves clinical effectiveness and to reveal its optimal use in non-small cell lung cancer (NSCLC), we systematically reevaluated all relevant studies.

Methods: We collected all studies about chemotherapy with CIK cells for NSCLC from the Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Data, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and U. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.011DOI Listing
February 2019
16 Reads

Response to Nature commentary "Clear up this stem-cell mess".

Cytotherapy 2019 Jan 12;21(1):1-2. Epub 2018 Dec 12.

University-Hospital of Modena and Reggio Emilia, Italy and Chair, ISCT Presidential Task Force on Unproven and Unethical Cell and Gene Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1016/j.jcyt.2018.11.007DOI Listing
January 2019
18 Reads

Evaluation of the differentiation status of neural stem cells based on cell morphology and the expression of Notch and Sox2.

Cytotherapy 2018 Dec 27;20(12):1472-1485. Epub 2018 Oct 27.

US Food & Drug Administration, Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Cellular and Gene Therapies, Silver Spring, Maryland, USA. Electronic address:

Neural stem cells (NSCs) isolated from a variety of sources are being developed as cellular therapies aimed at treating neurodegenerative diseases. During NSC culture and expansion it is important the cells do not differentiate prematurely because this may have an unfavorable effect on product quality and yield. In our study, we evaluated the use of Notch and Sox2 as markers for undifferentiated human and mouse NSCs. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.001DOI Listing
December 2018
2 Reads

Bioactive factors secreted from mesenchymal stromal cells protect the intestines from experimental colitis in a three-dimensional culture.

Cytotherapy 2018 Dec 27;20(12):1459-1471. Epub 2018 Oct 27.

Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. Electronic address:

Background Aims: Although mesenchymal stromal cells (MSCs) have shown therapeutic potential in intestinal tissue repair, controversy concerning their short survival and poor biodistribution in recipient tissues still remains. Therefore, we investigated the paracrine role of MSC in three-dimensional culture of colon with experimental colitis.

Methods: Colitis was induced in mice by oral administration of dextran sulfate sodium (DSS) for 7 days. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.06.007DOI Listing
December 2018
1 Read

Improvement of the folliculogenesis by transplantation of bone marrow mesenchymal stromal cells in mice with induced polycystic ovary syndrome.

Cytotherapy 2018 Dec 26;20(12):1445-1458. Epub 2018 Oct 26.

Department of Biology, Faculty of Science, Arak University, Arak, Iran.

Background: Many studies have reported that inflammation and oxidative stress are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Bone marrow mesenchymal stromal cells (BM-MSCs) have anti-oxidant and anti-inflammation properties. In this study, we investigate the beneficial effect of stem cell therapy on folliculogenesis in mice with induced PCOS METHODS: Mouse model of PCOS was performed through daily injection of testosterone enanthate (1 mg/100 g/body weight subcutaneous (s. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.09.005DOI Listing
December 2018
4 Reads

Safety and efficacy of allogenic placental mesenchymal stem cells for treating knee osteoarthritis: a pilot study.

Cytotherapy 2019 Jan 3;21(1):54-63. Epub 2018 Dec 3.

Cell-based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Pathology and Cell-based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: Knee osteoarthritis (OA) is a common skeletal impairment that can cause many limitations in normal life activities. Stem cell therapy has been studied for decades for its regenerative potency in various diseases. We investigated the safety and efficacy of intra-articular injection of placental mesenchymal stem cells (MSCs) in knee OA healing. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.003DOI Listing
January 2019
10 Reads
3.293 Impact Factor

Isolation of a novel embryonic stem cell cord blood-derived population with in vitro hematopoietic capacity in the presence of Wharton's jelly-derived mesenchymal stromal cells.

Cytotherapy 2019 Feb 4;21(2):246-259. Epub 2018 Dec 4.

Biohellenika Biotechnology Company, Thessaloniki, Greece; Department of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Recent studies highlight the existence of a population of cord blood (CB)-derived stem cells that bare embryonic features (very small embryonic-like stem cells [VSELs]) as the most primitive CB-stem cell population. In the present study, we present for the first time a novel and high purity isolation method of VSELs with in vitro hematopoietic capacity in the presence of Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs).

Methods: The experimental procedure includes isolation upon gradually increased centrifugation spins and chemotaxis to Stromal cell-derived factor 1a (SDF-1a). Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.006DOI Listing
February 2019
11 Reads
3.293 Impact Factor

Mesenchymal stromal cell therapy: progress in manufacturing and assessments of potency.

Cytotherapy 2019 Mar 6;21(3):289-306. Epub 2018 Dec 6.

The Arthritis Program, University Health Network, Toronto, Canada;; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada; Cell Therapy Program, University Health Network, Toronto, Canada; Division of Hematology, Department of Medicine, University of Toronto, Toronto, Canada. Electronic address:

Mesenchymal stromal cell (MSC) therapies have been pursued for a broad spectrum of indications but mixed reports on clinical efficacy have given rise to some degree of skepticism regarding the effectiveness of this approach. However, recent reports of successful clinical outcomes and regulatory approvals for graft-versus-host disease, Crohn's disease and critical limb ischemia have prompted a shift in this perspective. With hundreds of clinical trials involving MSCs currently underway and an increasing demand for large-scale manufacturing protocols, there is a critical need to develop standards that can be applied to processing methods and to establish consensus assays for both MSC processing control and MSC product release. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.014DOI Listing
March 2019
11 Reads

Morphological profiling using machine learning reveals emergent subpopulations of interferon-γ-stimulated mesenchymal stromal cells that predict immunosuppression.

Cytotherapy 2019 Jan 28;21(1):17-31. Epub 2018 Nov 28.

Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address:

Background: Although a preponderance of pre-clinical data demonstrates the immunosuppressive potential of mesenchymal stromal cells (MSCs), significant heterogeneity and lack of critical quality attributes (CQAs) based on immunosuppressive capacity likely have contributed to inconsistent clinical outcomes. This heterogeneity exists not only between MSC lots derived from different donors, tissues and manufacturing conditions, but also within a given MSC lot in the form of functional subpopulations. We therefore explored the potential of functionally relevant morphological profiling (FRMP) to identify morphological subpopulations predictive of the immunosuppressive capacity of MSCs derived from multiple donors, manufacturers and passages. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.008DOI Listing
January 2019
16 Reads

A simple and efficient method for cultivation of limbal explant stem cells with clinically safe potential.

Cytotherapy 2019 Jan 30;21(1):83-95. Epub 2018 Nov 30.

Institute of Science and Engineering, Bioengineering, Hacettepe University, Ankara, Turkey; Faculty of Engineering, Chemical Engineering Department, Hacettepe University, Ankara, Turkey. Electronic address:

Background: Several methods to cultivate limbal epithelial stem cells (LESCs) in vitro with the support of feeder layers and different growth medium formulations have been established for several years. The initial green medium consists of various ingredients that exhibit a non-optimal level of biosafety, therefore, different modifications have been made to suit it to safe clinical applications. However, the question of which formulation is the most appropriate remains to be answered. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.005DOI Listing
January 2019
11 Reads

Tumor-infiltrating lymphocytes: Streamlining a complex manufacturing process.

Cytotherapy 2019 Mar 1;21(3):307-314. Epub 2018 Dec 1.

Cellular Therapy Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

Adoptive cell therapy of tumor-infiltrating lymphocytes has shown promise for treatment of refractory melanoma and other solid malignancies; however, challenges to manufacturing have limited its widespread use. Traditional manufacturing efforts were lengthy, cumbersome and used open culture systems. We describe changes in testing and manufacturing that decreased the process cycle time, enhanced the robustness of critical quality attribute testing and facilitated a functionally closed system. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453723PMC
March 2019
1 Read

Closed loop bioreactor system for the ex vivo expansion of human T cells.

Cytotherapy 2019 Jan 27;21(1):76-82. Epub 2018 Nov 27.

Center for Surgery, Innovation, and Bioengineering, Department of Surgery, Massachusetts General Hospital and the Shriners Hospitals for Children, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA; Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA. Electronic address:

Background Aim: Translation of therapeutic cell therapies to clinical-scale products is critical to realizing widespread success. Currently, however, there are limited tools that are accessible at the research level and readily scalable to clinical-scale needs.

Methods: We herein developed and assessed a closed loop bioreactor system in which (i) a highly gas-permeable silicone material was used to fabricate cell culture bags and (ii) dynamic flow was introduced to allow for dissociation of activated T-cell aggregates. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333522PMC
January 2019
2 Reads

Mesenchymal stem cells preconditioned by staphylococcal enterotoxin B enhance survival and bacterial clearance in murine sepsis model.

Cytotherapy 2019 Jan 23;21(1):41-53. Epub 2018 Nov 23.

Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

Sepsis, a health-threatening progressive infectious disease, is the major cause of morbidity and mortality worldwide. Cell therapy using mesenchymal stromal cells (MSCs) is an innovative strategy with excessive therapeutic potential in the treatment of sepsis. Staphylococcal enterotoxin B (SEB) preconditioning aims to prolong the interval of survival of transplanted MSCs which induces the production of cytoprotective agents, anti-apoptotic and anti-inflammatory factors. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.11.002DOI Listing
January 2019
2 Reads

Cell sheet technology: a promising strategy in regenerative medicine.

Cytotherapy 2019 Jan 22;21(1):3-16. Epub 2018 Nov 22.

Department of Burns, Nanfang Hospital, Southern Medical University, Baiyun District, Guangzhou, People's Republic of China. Electronic address:

Regenerative medicine is a burgeoning field that is important to combat challenging diseases and functional impairments. Compared with traditional cell therapies with evident shortcomings (e.g. Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.013DOI Listing
January 2019
14 Reads

Optimizing the transport and storage conditions of current Good Manufacturing Practice -grade human umbilical cord mesenchymal stromal cells for transplantation (HUC-HEART Trial).

Cytotherapy 2019 Jan 16;21(1):64-75. Epub 2018 Nov 16.

Department of Histology and Embryology, Faculty of Medicine, Ankara University, Ankara, Turkey. Electronic address:

Background: The HUC-HEART Trial is a clinical study of intramyocardial delivery of current Good Manufacturing Practice (cGMP)-grade human umbilical cord multipotent stromal cells (HUC-MSCs) in ischemic cardiomyopathy where 2 × 10 cells are administered to peri-infarcted myocardium. Prior to the onset of the trial, we aimed to optimize the transport/storage conditions for obtaining the highest cell viability and proliferation rate of cells to be transplanted.

Methods: Cells were tested after being transported in phosphate-buffered saline (PBS) or Ringer's lactate-based (RL) transport media supplemented with human serum albumin (HSA) and/or hydroxyethyl starch (HES) at two temperatures (2-10°C or 22-24°C). Read More

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http://dx.doi.org/10.1016/j.jcyt.2018.10.010DOI Listing
January 2019
18 Reads