10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Directing and Potentiating Stem Cell-Mediated Angiogenesis and Tissue Repair by Cell Surface E-Selectin Coating

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Stem cell therapy has emerged as a promising approach for treatment of a number of diseases, including delayed and non-healing wounds. However, targeted systemic delivery of therapeutic cells to the dysfunctional tissues remains one formidable challenge. Herein, we present a targeted nanocarrier-mediated cell delivery method by coating the surface of the cell to be delivered with dendrimer nanocarriers modified with adhesion molecules. Infused nanocarrier-coated cells reach to destination via recognition and association with the counterpart adhesion molecules highly or selectively expressed on the activated endothelium in diseased tissues. Once anchored on the activated endothelium, nanocarriers-coated transporting cells undergo transendothelial migration, extravasation and homing to the targeted tissues to execute their therapeutic role. We now demonstrate feasibility, efficacy and safety of our targeted nanocarrier for delivery of bone marrow cells (BMC) to cutaneous wound tissues and grafted corneas and its advantages over conventional BMC transplantation in mouse models for wound healing and neovascularization. This versatile platform is suited for targeted systemic delivery of virtually any type of therapeutic cell.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

          Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions. In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. clinicaltrials.gov Identifier: NCT01087996.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Engineering targeted viral vectors for gene therapy

            Key Points Translating knowledge of genetic disease mechanisms into gene therapies has been slow with limited clinical success. One major reason is that the transfer vectors, which are most often of viral origin, are not targeted sufficiently towards the cells of interest. To achieve successful delivery of genetic material, transductional targeting is often essential to enter the target cell and to avoid side effects from the transduction of non-target cells. Many techniques to target viral vectors to specific cells have been developed. They can be divided into three types: systems that use adaptor proteins from other viruses (pseudotyping); systems that use adaptors to couple the targeting ligand to the vector; and systems that genetically incorporate the targeting moiety into the viral genome. Whereas systems involving adaptor proteins are highly useful in preclinical evaluations, systems that make use of genetically incorporated targeting ligands are advantageous for clinical applications. Combinations of several targeting principles (including ablation of natural tropism, pseudotyping and adaptors) and novel combinations (such as the adeno-associated virus (AAV) genome in a phage vector) allow systemic vector application. An initial clinical study with a targeted retrovirus showed feasibility to transfer laboratory success to patient application, underlining that there are no principal regulatory barriers for targeted vectors. Systemic vector applications will be facilitated by enabling the vector to move beyond the vascular endothelium at specific sites, using transcytosis or cellular vehicles. The application of existing targeting techniques to new viral vector serotypes and new vector classes is extending the therapeutic capabilities further. Obstacles to systemic application of vectors are found in the blood as immune reactions against the vector and as binding of blood proteins to the vector. Some targeting approaches might have the potential to circumvent these obstacles. To preclinically evaluate new targeting strategies, several models that reflect the human situation to varying degrees are available. The use of primary cells, tissue-slice systems and transgenic animals seems to be especially promising. Imaging technologies provide the ability to monitor the vector in vivo in real time without sacrificing the animal model. These techniques facilitate vector targeting and biodistribution studies.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              MSCs: Delivery Routes and Engraftment, Cell-Targeting Strategies, and Immune Modulation

              Mesenchymal stem cells (MSCs) are currently being widely investigated both in the lab and in clinical trials for multiple disease states. The differentiation, trophic, and immunomodulatory characteristics of MSCs contribute to their therapeutic effects. Another often overlooked factor related to efficacy is the degree of engraftment. When reported, engraftment is generally low and transient in nature. MSC delivery methods should be tailored to the lesion being treated, which may be local or systemic, and customized to the mechanism of action of the MSCs, which can also be local or systemic. Engraftment efficiency is enhanced by using intra-arterial delivery instead of intravenous delivery, thus avoiding the “first-pass” accumulation of MSCs in the lung. Several methodologies to target MSCs to specific organs are being developed. These cell targeting methodologies focus on the modification of cell surface molecules through chemical, genetic, and coating techniques to promote selective adherence to particular organs or tissues. Future improvements in targeting and delivery methodologies to improve engraftment are expected to improve therapeutic results, extend the duration of efficacy, and reduce the effective (MSC) therapeutic dose.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 April 2016
                2016
                : 11
                : 4
                : e0154053
                Affiliations
                [1 ]Department of Surgery, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America
                [2 ]Department of Biochemistry and Molecular Biology, School of Medicine, University of Miami, Coral Gables, Florida, 33136, United States of America
                [3 ]Dr. JT Macdonald Biomedical Nanotechnology Institute, University of Miami, Coral Gables, Florida, 33136, United States of America
                [4 ]Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Coral Gables, Florida, 33136, United States of America
                Universidad de Castilla-La Mancha, SPAIN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ZL PD S Deo S Daunert OV. Performed the experiments: PD LK BW RT DC ED. Analyzed the data: PD LK BW RT DC ED ZL VP S Deo S Daunert OV. Contributed reagents/materials/analysis tools: ZL PD VP S Deo. Wrote the paper: ZL PD S Deo S Daunert OV. Administrative, technical, or material support: ZL PD VP S Deo.

                Article
                PONE-D-15-49145
                10.1371/journal.pone.0154053
                4841581
                27104647
                29dd0673-2ebc-4291-b9a7-a7af0972c179
                © 2016 Liu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 November 2015
                : 7 April 2016
                Page count
                Figures: 7, Tables: 0, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
                Award ID: R01DK-071084
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: R01GM081570
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: R01GM047915
                Award Recipient :
                This work was supported by grants from the National Institutes of Health (R01DK-071084 and R01GM081570 to OV and R01GM047915 to SD). OV is grateful for funding from the David Kimmelman Endowed Chair in Vascular Surgery and SD is also grateful for support by the Lucille P. Markey Chair in Department of Biochemistry and Molecular Biology.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Stem Cells
                Mesenchymal Stem Cells
                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Endothelium
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Endothelium
                Biology and Life Sciences
                Biophysics
                Bionanotechnology
                Physical Sciences
                Physics
                Biophysics
                Bionanotechnology
                Biology and Life Sciences
                Biotechnology
                Bionanotechnology
                Engineering and Technology
                Nanotechnology
                Bionanotechnology
                Physical Sciences
                Materials Science
                Materials by Attribute
                Coatings
                Engineering and Technology
                Manufacturing Processes
                Surface Treatments
                Coatings
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Tissue Repair
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Tissue Repair
                Medicine and Health Sciences
                Clinical Genetics
                Stem Cell Therapy
                Physical Sciences
                Materials Science
                Materials by Structure
                Thin Films
                Custom metadata
                All relevant data are within the paper and its Supporting Information files (Supplemental Information).

                Uncategorized
                Uncategorized

                Comments

                Comment on this article