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Northwood, United Kingdom

As collagen is the main structural component of connective tissues and skin, much effort was made in the past and still today to use it in cell culture applications. Moreover, collagen biomaterials are widely used in tissue regeneration, including the treatment of burns and chronic wounds. The great implications of the research carried out by Bornstein, Ehrmann and Gey on collagen preparations in the 1950s for cell culture and more recently tissue engineering and regeneration are described in this commentary. Specifically, it is explored why the 1958 paper on 'Reconstituted Rat-Tail Collagen Used as Substrate for Tissue Cultures on Coverslips in Maximow Slides and Roller Tubes' by M. B. Bornstein has made an invaluable contribution to the field. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source


Kaufmann J.K.,German Cancer Research Center | Kaufmann J.K.,University of Heidelberg | Bossow S.,German Cancer Research Center | Grossardt C.,German Cancer Research Center | And 10 more authors.
Journal of Investigative Dermatology | Year: 2013

Effective treatment modalities for advanced melanoma are desperately needed. An innovative approach is virotherapy, in which viruses are engineered to infect cancer cells, resulting in tumor cell lysis and an amplification effect by viral replication and spread. Ideally, tumor selectivity of these oncolytic viruses is already determined during viral cell binding and entry, which has not been reported for melanoma. We engineered an oncolytic measles virus entering melanoma cells through the high molecular weight melanoma-associated antigen (HMWMAA) and proved highly specific infection and spread in melanoma cells. We further enhanced this oncolytic virus by inserting the FCU1 gene encoding the yeast-derived prodrug convertases cytosine deaminase and uracil phosphoribosyltransferase. Combination treatment with armed and retargeted MV-FCU1-HMWMAA and the prodrug 5-fluorocytosine (5-FC) led to effective prodrug conversion to 5-fluorouracil, extensive cytotoxicity to melanoma cells, and excessive bystander killing of noninfected cells. Importantly, HMWMAA-retargeted MV showed antitumor activity in a human xenograft mouse model, which was further increased by the FCU1/5-FC prodrug activation system. Finally, we demonstrated susceptibility of melanoma skin metastasis biopsies to HMWMAA-retargeted MV. The highly selective, entry-targeted and armed oncolytic virus MV-FCU1-HMWMAA may become a potent building block of future melanoma therapies. © 2013 The Society for Investigative Dermatology. Source


Reissis Y.,Imperial College London | Garcia-Gareta E.,RAFT Institute of Plastic Surgery | Korda M.,UCL Institute of Orthopaedics and Musculoskeletal Science | Blunn G.W.,UCL Institute of Orthopaedics and Musculoskeletal Science | Hua J.,UCL Institute of Orthopaedics and Musculoskeletal Science
Stem Cell Research and Therapy | Year: 2013

Introduction. Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs. Methods. The viability of human MSCs was measured after incubating them at temperatures of 38°C, 48°C and 58°C; durations 45 seconds, 80 seconds and 150 seconds. A control group was kept at 37°C and 5% carbon dioxide for the duration of the investigation (7 days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlue™ assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnett's test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlue™) and cell viability (Trypan Blue). Results: Results showed that cell metabolism was not severely affected up to 48°C/150 seconds, while cells in the 58°C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48°C/150 seconds were compared with the control group. Conclusions: The study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48°C for 150 seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations. © 2013 Reissis et al.; licensee BioMed Central Ltd. Source


Garcia-Gareta E.,RAFT Institute of Plastic Surgery | Coathup M.J.,University College London | Blunn G.W.,University College London
Bone | Year: 2015

Regeneration of bone defects caused by trauma, infection, tumours or inherent genetic disorders is a clinical challenge that usually necessitates bone grafting materials. Autologous bone or autograft is still considered the clinical "gold standard" and the most effective method for bone regeneration. However, limited bone supply and donor site morbidity are the most important disadvantages of autografting. Improved biomaterials are needed to match the performance of autograft as this is still superior to that of synthetic bone grafts. Osteoinductive materials would be the perfect candidates for achieving this task. The aim of this article is to review the different groups of bone substitutes in terms of their most recently reported osteoinductive properties. The different factors influencing osteoinductivity by biomaterials as well as the mechanisms behind this phenomenon are also presented, showing that it is very limited compared to osteoinductivity shown by bone morphogenetic proteins (BMPs). Therefore, a new term to describe osteoinductivity by biomaterials is proposed. Different strategies for adding osteoinductivity (BMPs, stem cells) to bone substitutes are also discussed. The overall objective of this paper is to gather the current knowledge on osteoinductivity of bone grafting materials for the effective development of new graft substitutes that enhance bone regeneration. © 2015 Elsevier Inc. Source


Sharma V.,RAFT Institute of Plastic Surgery | Sharma V.,University College London | Patel N.,RAFT Institute of Plastic Surgery | Dye J.F.,RAFT Institute of Plastic Surgery | And 3 more authors.
Biochimie Open | Year: 2015

Commercially available two component human fibrin sealants are commonly used to manufacture human fibrin-based biomaterials. However, this method is costly and allows little room for further tuning of the biomaterial. Human fibrinogen solutions offer a more cost-effective and versatile alternative to manufacture human fibrin-based biomaterials. Yet, human fibrinogen is highly unstable and contains certain impurities like human albumin. Within the context of biomaterials and tissue engineering we offer a simple yet novel solution based on classical biochemical techniques to significantly reduce albumin in human fibrinogen solutions. This method can be used for various tissue engineering and biomedical applications as an initial step in the manufacturing of human fibrin-based biomaterials to optimise their regenerative application. © 2015 The Authors. Published by Elsevier B.V. Source

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