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Goulart LT, Matsunaga FT, Belloti JC, Netto NA, Paim TS, Tamaoki MJS. Effectiveness of sub-acromial injections in rotator cuff injuries: A systematic review and meta-analysis. World J Orthop 2025; 16:102856. [PMID: 40027967 PMCID: PMC11866104 DOI: 10.5312/wjo.v16.i2.102856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/20/2024] [Accepted: 01/17/2025] [Indexed: 02/12/2025] Open
Abstract
BACKGROUND Sub-acromial injections are a therapeutic option for rotator cuff injuries; however, evidence regarding the most effective drug in this context is unclear, which needs to be investigated. AIM To evaluate the effectiveness of various sub-acromial injections for rotator cuff injuries. METHODS We conducted a systematic review and pair-wise and network meta-analyses of randomized clinical trials (RCTs) comparing sub-acromial injections for rotator cuff injuries. The interventions evaluated were hyaluronic acid (HA), platelet-rich plasma (PRP), prolotherapy, and corticosteroids. The outcomes of interest were pain and functional improvement, which were evaluated with standardized scores. The Risk of Bias 2 tool and the Grading of Recommendations, Assessment, Development and Evaluation methodology were used to assess data quality. RESULTS Twenty RCTs, comprising 1479 participants, were included. In the short term, HA achieved the best outcomes [pain mean difference (MD) = -1.48, 95% confidence interval (CI) -2.37 to -0.59; function MD = 10.18, 95%CI: 4.96-15.41]. In the medium term, HA, PRP, HA + PRP, and corticosteroids were not superior to placebo in improving pain. Based on function, HA + PRP was superior to placebo, corticosteroids, and PRP (MD = 26.72; 95%CI: 8.02-45.41). In the long term, HA, PRP, and corticosteroids were not superior to placebo in reducing pain. However, based on function, HA + PRP, PRP, and HA were superior to placebo, and HA + PRP had the best result (MD = 36.64; 95%CI: 31.66-33.62). CONCLUSION HA provides satisfactory short-term results, while HA with PRP demonstrates functional improvement in the medium and long terms. However, no intervention maintained the pain-relief effect on > 3-month follow-up.
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Affiliation(s)
- Luana Tossolini Goulart
- Department of Orthopedics and Trauma, Federal University of São Paulo-Paulista School of Medicine, São Paulo 04023-062, Brazil
| | - Fabio Teruo Matsunaga
- Department of Orthopedics and Trauma, Federal University of São Paulo-Paulista School of Medicine, São Paulo 04023-062, Brazil
| | - Joao Carlos Belloti
- Department of Orthopedics and Trauma, Federal University of São Paulo-Paulista School of Medicine, São Paulo 04023-062, Brazil
| | - Nicola Archetti Netto
- Department of Orthopedics and Trauma, Federal University of São Paulo-Paulista School of Medicine, São Paulo 04023-062, Brazil
| | - Thays Sellan Paim
- Department of Orthopedics and Trauma, Federal University of São Paulo-Paulista School of Medicine, São Paulo 04023-062, Brazil
| | - Marcel Jun Sugawara Tamaoki
- Department of Orthopedics and Trauma, Federal University of São Paulo-Paulista School of Medicine, São Paulo 04023-062, Brazil
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Therapeutic Potential of Skin Stem Cells and Cells of Skin Origin: Effects of Botanical Drugs Derived from Traditional Medicine. Stem Cell Rev Rep 2022; 18:1986-2001. [PMID: 35648312 DOI: 10.1007/s12015-022-10388-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/12/2022] [Indexed: 12/09/2022]
Abstract
Skin, the largest organ of the body, plays a vital role in protecting inner organs. Skin stem cells (SSCs) comprise a group of cells responsible for multiplication and replacement of damaged and non-functional skin cells; thereby help maintain homeostasis of skin functions. SSCs and differentiated cells of the skin such as melanocytes and keratinocytes, have a plethora of applications in regenerative medicine. However, as SSCs reside in small populations in specific niches in the skin, use of external stimulants for cell proliferation in vitro and in vivo is vital. Synthetic and recombinant stimulants though available, pose many challenges due to their exorbitant prices, toxicity issues and side effects. Alternatively, time tested traditional medicine preparations such as polyherbal formulations are widely tested as effective natural stimulants, to mainly stimulate proliferation, and melanogenesis/prevention of melanogenesis of both SSCs and cells of skin origin. Complex, multiple targets, synergistic bioactivities of the phytochemical constituents of herbal preparations amply justify these as natural stimulants. The use of these formulations in clinical applications such as in skin regeneration for burn wounds, wound healing acceleration, enhancement or decrease of melanin pigmentations will be in great demand. Although much multidisciplinary research is being conducted on the use of herbal formulas as stem cell stimulants, very few related clinical trials are yet registered with the NIH clinical trial registry. Therefore, identification/ discovery, in depth investigations culminating in clinical trials, as well as standardization and commercialization of such natural stimulants must be promoted, ensuring the sustainable use of medicinal plants.
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Abolarinwa BA, Shaw MK, Lee CH. Perspectives on Challenges to Cell Therapy Development in Taiwan: Strengthening Evidential Standards and Ways Forward. Front Bioeng Biotechnol 2021; 9:789043. [PMID: 34976978 PMCID: PMC8716849 DOI: 10.3389/fbioe.2021.789043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 11/29/2021] [Indexed: 11/13/2022] Open
Abstract
Over the past years, the field of regenerative medicine and cell therapy has garnered much interest, extending beyond the bench to broader use, and commercialization. These therapies undergo stringent regulatory oversight as a result of their complexities and potential risk across different jurisdictions. Taiwan’s government, with the aim of developing the country as a hub for regenerative medicine in Asia, enacted a dual track act to promote the development of regenerative and cell therapy products. This qualitative study used purposive sampling to recruit sixteen experts (Twelve respondents from medical institutions and four respondents from the industry) to understand their perspectives on one of the regulatory tracks which governs the medical use of cell technologies and challenges regarding its implementation. Semi-structured interviews were conducted, transcribed, coded and thematically analyzed. Three major themes emerged from the analysis: 1) Perceptions of the “Special Regulation for Cell Therapy” 2) Emerging issues and controversies on the medical use of cell technologies in private clinics, and 3) Challenges impeding the clinical innovation of cell technologies. As reported by the experts, it was clear that the special regulation for cell therapy was aimed at legalizing the clinical use of cell therapy in a similar fashion to an evidence-based pathway, to promote clinical innovation, ensure manufacturing consistency, and improve oversight on cell-based therapies. Thus, the regulation addresses the issues of safety concerns, patient’s access and stem cell tourism. However, the limited approved cell techniques, quality control during cell processing, time, and criteria used in evaluating applications in addition to the need to develop evidential standards for clinical evidence are some of the difficulties faced. Thus, policy interventions on funding, educational resources, training, and regulatory clarity addressing these challenges may positively impact clinical innovation of cell therapy in Taiwan.
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Affiliation(s)
- Bilikis Aderonke Abolarinwa
- International PhD program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Malissa Kay Shaw
- Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Chung-Hsi Lee
- International PhD program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Health and Biotechnology Law, Taipei Medical University, Taipei, Taiwan
- *Correspondence: Chung-Hsi Lee,
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4
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Ma Y, Gao L, Tian Y, Chen P, Yang J, Zhang L. Advanced biomaterials in cell preservation: Hypothermic preservation and cryopreservation. Acta Biomater 2021; 131:97-116. [PMID: 34242810 DOI: 10.1016/j.actbio.2021.07.001] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 02/07/2023]
Abstract
Cell-based medicine has made great advances in clinical diagnosis and therapy for various refractory diseases, inducing a growing demand for cell preservation as support technology. However, the bottleneck problems in cell preservation include low efficiency and poor biocompatibility of traditional protectants. In this review, cell preservation technologies are categorized according to storage conditions: hypothermic preservation at 1 °C~35 °C to maintain short-term cell viability that is useful in cell diagnosis and transport, while cryopreservation at -196 °C~-80 °C to maintain long-term cell viability that provides opportunities for therapeutic cell product storage. Firstly, the background and developmental history of the protectants used in the two preservation technologies are briefly introduced. Secondly, the progress in different cellular protection mechanisms for advanced biomaterials are discussed in two preservation technologies. In hypothermic preservation, the hypothermia-induced and extracellular matrix-loss injuries to cells are comprehensively summarized, as well as the recent biomaterials dependent on regulation of cellular ATP level, stabilization of cellular membrane, balance of antioxidant defense system, and supply of mimetic ECM to prolong cell longevity are provided. In cryopreservation, cellular injuries and advanced biomaterials that can protect cells from osmotic or ice injury, and alleviate oxidative stress to allow cell survival are concluded. Last, an insight into the perspectives and challenges of this technology is provided. We envision advanced biocompatible materials for highly efficient cell preservation as critical in future developments and trends to support cell-based medicine. STATEMENT OF SIGNIFICANCE: Cell preservation technologies present a critical role in cell-based applications, and more efficient biocompatible protectants are highly required. This review categorizes cell preservation technologies into hypothermic preservation and cryopreservation according to their storage conditions, and comprehensively reviews the recently advanced biomaterials related. The background, development, and cellular protective mechanisms of these two preservation technologies are respectively introduced and summarized. Moreover, the differences, connections, individual demands of these two technologies are also provided and discussed.
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Affiliation(s)
- Yiming Ma
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, PR China; Frontier Technology Research Institute, Tianjin University, Tianjin 300350, PR China
| | - Lei Gao
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, PR China; Frontier Technology Research Institute, Tianjin University, Tianjin 300350, PR China
| | - Yunqing Tian
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, PR China; Frontier Technology Research Institute, Tianjin University, Tianjin 300350, PR China
| | - Pengguang Chen
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, PR China; Frontier Technology Research Institute, Tianjin University, Tianjin 300350, PR China
| | - Jing Yang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, PR China; Frontier Technology Research Institute, Tianjin University, Tianjin 300350, PR China.
| | - Lei Zhang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, PR China; Frontier Technology Research Institute, Tianjin University, Tianjin 300350, PR China.
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5
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Rubanenko M, Manturova N, Ustiugov A, Porshina O, Petunina V, Zorin V, Zorina A, Palinkash A. Epidermolysis bullosa. Possible methods of treatment. KLINICHESKAYA DERMATOLOGIYA I VENEROLOGIYA 2021; 20:22. [DOI: 10.17116/klinderma20212004122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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6
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Las Heras K, Igartua M, Santos-Vizcaino E, Hernandez RM. Chronic wounds: Current status, available strategies and emerging therapeutic solutions. J Control Release 2020; 328:532-550. [DOI: 10.1016/j.jconrel.2020.09.039] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 02/07/2023]
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7
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Gao Y, Jin SZ. Strategies for treating oesophageal diseases with stem cells. World J Stem Cells 2020; 12:488-499. [PMID: 32742566 PMCID: PMC7360987 DOI: 10.4252/wjsc.v12.i6.488] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 05/02/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
There is a wide range of oesophageal diseases, the most general of which are inflammation, injury and tumours, and treatment methods are constantly being developed and updated. With an increasingly comprehensive understanding of stem cells and their characteristics of multilineage differentiation, self-renewal and homing as well as the combination of stem cells with regenerative medicine, tissue engineering and gene therapy, stem cells are playing an important role in the treatment of a variety of diseases. Mesenchymal stem cells have many advantages and are most commonly applied; however, most of these applications have been in experimental studies, with few related clinical trials for comparison. Therefore, the methods, positive significance and limitations of stem cells in the treatment of oesophageal diseases remain incompletely understood. Thus, the purpose of this paper is to review the current literature and summarize the efficacy of stem cells in the treatment of oesophageal diseases, including oesophageal ulceration, acute radiation-induced oesophageal injury, corrosive oesophageal injury, oesophageal stricture formation after endoscopic submucosal dissection and oesophageal reconstruction, as well as gene therapy for oesophageal cancer.
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Affiliation(s)
- Yang Gao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Shi-Zhu Jin
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
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8
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Jacques E, Suuronen EJ. The Progression of Regenerative Medicine and its Impact on Therapy Translation. Clin Transl Sci 2020; 13:440-450. [PMID: 31981408 PMCID: PMC7214652 DOI: 10.1111/cts.12736] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 11/07/2019] [Indexed: 12/14/2022] Open
Abstract
Despite regenerative medicine (RM) being one of the hottest topics in biotechnology for the past 3 decades, it is generally acknowledged that the field's performance at the bedside has been somewhat disappointing. This may be linked to the novelty of these technologies and their disruptive nature, which has brought an increasing level of complexity to translation. Therefore, we look at how the historical development of the RM field has changed the translational strategy. Specifically, we explore how the pursuit of such novel regenerative therapies has changed the way experts aim to translate their ideas into clinical applications, and then identify areas that need to be corrected or reinforced in order for these therapies to eventually be incorporated into the standard-of-care. This is then linked to a discussion of the preclinical and postclinical challenges remaining today, which offer insights that can contribute to the future progression of RM.
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Affiliation(s)
- Erik Jacques
- Division of Cardiac SurgeryUniversity of Ottawa Heart InstituteOttawaOntarioCanada
- School of Human KineticsUniversity of OttawaOttawaCanada
| | - Erik J. Suuronen
- Division of Cardiac SurgeryUniversity of Ottawa Heart InstituteOttawaOntarioCanada
- Department of Cellular & Molecular MedicineUniversity of OttawaOttawaCanada
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9
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Functional Role of Circular RNA in Regenerative Medicine. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1087:299-308. [PMID: 30259376 DOI: 10.1007/978-981-13-1426-1_24] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Every year, millions of people around the world suffer from different forms of tissue trauma. Regenerative medicine refers to therapy that replaces the injured organ or cells. Stem cells are the frontiers and hotspots of current regenerative medicine research. Circular RNAs (circRNAs) are essential for the early development of many species. It was found that they could guide stem cell differentiation through interacting with certain microRNAs (miRNAs). Based on this concept, it is meaningful to look into how circRNAs influence stem cells and its role in regenerative medicine. In this chapter we will discuss the functional roles of circRNAs in the prevention, repair, or progression of chronic diseases, through the communication between stem cells.
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10
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Enhancing cell and gene therapy manufacture through the application of advanced fluorescent optical sensors (Review). Biointerphases 2017; 13:01A301. [PMID: 29246035 DOI: 10.1116/1.5013335] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Cell and gene therapies (CGTs) are examples of future therapeutics that can be used to cure or alleviate the symptoms of disease, by repairing damaged tissue or reprogramming defective genetic information. However, despite the recent advancements in clinical trial outcomes, the path to wide-scale adoption of CGTs remains challenging, such that the emergence of a "blockbuster" therapy has so far proved elusive. Manufacturing solutions for these therapies require the application of scalable and replicable cell manufacturing techniques, which differ markedly from the existing pharmaceutical incumbent. Attempts to adopt this pharmaceutical model for CGT manufacture have largely proved unsuccessful. The most significant challenges facing CGT manufacturing are process analytical testing and quality control. These procedures would greatly benefit from improved sensory technologies that allow direct measurement of critical quality attributes, such as pH, oxygen, lactate and glucose. In turn, this would make manufacturing more robust, replicable and standardized. In this review, the present-day state and prospects of CGT manufacturing are discussed. In particular, the authors highlight the role of fluorescent optical sensors, focusing on their strengths and weaknesses, for CGT manufacture. The review concludes by discussing how the integration of CGT manufacture and fluorescent optical sensors could augment future bioprocessing approaches.
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11
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Scarfe L, Brillant N, Kumar JD, Ali N, Alrumayh A, Amali M, Barbellion S, Jones V, Niemeijer M, Potdevin S, Roussignol G, Vaganov A, Barbaric I, Barrow M, Burton NC, Connell J, Dazzi F, Edsbagge J, French NS, Holder J, Hutchinson C, Jones DR, Kalber T, Lovatt C, Lythgoe MF, Patel S, Patrick PS, Piner J, Reinhardt J, Ricci E, Sidaway J, Stacey GN, Starkey Lewis PJ, Sullivan G, Taylor A, Wilm B, Poptani H, Murray P, Goldring CEP, Park BK. Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies. NPJ Regen Med 2017; 2:28. [PMID: 29302362 PMCID: PMC5677988 DOI: 10.1038/s41536-017-0029-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 06/30/2017] [Accepted: 07/24/2017] [Indexed: 02/08/2023] Open
Abstract
Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies. To facilitate clinical translation, non-invasive in vivo imaging technologies that enable careful evaluation and characterisation of the administered cells and their effects on host tissues are critically required to evaluate their safety and efficacy in relevant preclinical models. This article reviews the most common imaging technologies available and how they can be applied to regenerative medicine research. We cover details of how each technology works, which cell labels are most appropriate for different applications, and the value of multi-modal imaging approaches to gain a comprehensive understanding of the responses to cell therapy in vivo.
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Affiliation(s)
- Lauren Scarfe
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
- Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK
| | - Nathalie Brillant
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
- Medical Research Council Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
| | - J. Dinesh Kumar
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
| | - Noura Ali
- College of Health Science, University of Duhok, Duhok, Iraq
| | - Ahmed Alrumayh
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
| | - Mohammed Amali
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
| | - Stephane Barbellion
- Medical Research Council Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
| | - Vendula Jones
- GlaxoSmithKline, David Jack Centre for Research and Development, Ware, UK
| | - Marije Niemeijer
- Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands
| | - Sophie Potdevin
- SANOFI Research and Development, Disposition, Safety and Animal Research, Alfortville, France
| | - Gautier Roussignol
- SANOFI Research and Development, Disposition, Safety and Animal Research, Alfortville, France
| | - Anatoly Vaganov
- Department of Biology, University of Konstanz, Konstanz, Germany
| | - Ivana Barbaric
- Department of Biomedical Science, University of Sheffield, Sheffield, UK
| | - Michael Barrow
- Department of Chemistry, University of Liverpool, Liverpool, UK
| | | | - John Connell
- Centre for Advanced Biomedical Imaging, University College London, London, UK
| | - Francesco Dazzi
- Department of Haemato-Oncology, King’s College London, London, UK
| | | | - Neil S. French
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
| | - Julie Holder
- Roslin Cells, University of Cambridge, Cambridge, UK
| | - Claire Hutchinson
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
- Medical Research Council Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
| | - David R. Jones
- Medicines and Healthcare Products Regulatory Agency, London, UK
| | - Tammy Kalber
- Centre for Advanced Biomedical Imaging, University College London, London, UK
| | - Cerys Lovatt
- GlaxoSmithKline, David Jack Centre for Research and Development, Ware, UK
| | - Mark F. Lythgoe
- Centre for Advanced Biomedical Imaging, University College London, London, UK
| | - Sara Patel
- ReNeuron Ltd, Pencoed Business Park, Pencoed, Bridgend, UK
| | - P. Stephen Patrick
- Centre for Advanced Biomedical Imaging, University College London, London, UK
| | - Jacqueline Piner
- GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, UK
| | | | - Emanuelle Ricci
- Institute of Veterinary Science, University of Liverpool, Liverpool, UK
| | | | - Glyn N. Stacey
- UK Stem Cell Bank, Division of Advanced Therapies, National Institute for Biological Standards Control, Medicines and Healthcare Products Regulatory Agency, London, UK
| | - Philip J. Starkey Lewis
- Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - Gareth Sullivan
- Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
- Norwegian Center for Stem Cell Research, Blindern, Oslo, Norway
- Institute of Immunology, Oslo University Hospital-Rikshospitalet, Nydalen, Oslo, Norway
- Hybrid Technology Hub—Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, Blindern, Oslo, Norway
| | - Arthur Taylor
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
- Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK
| | - Bettina Wilm
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
- Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK
| | - Harish Poptani
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
- Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK
| | - Patricia Murray
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
- Centre for Preclinical Imaging, University of Liverpool, Liverpool, UK
| | - Chris E. P. Goldring
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
- Medical Research Council Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
| | - B. Kevin Park
- Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
- Medical Research Council Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
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12
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Davies BM, Smith J, Rikabi S, Wartolowska K, Morrey M, French A, MacLaren R, Williams D, Bure K, Pinedo-Villanueva R, Mathur A, Birchall M, Snyder E, Atala A, Reeve B, Brindley D. A quantitative, multi-national and multi-stakeholder assessment of barriers to the adoption of cell therapies. J Tissue Eng 2017; 8:2041731417724413. [PMID: 28835816 PMCID: PMC5557158 DOI: 10.1177/2041731417724413] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Accepted: 07/14/2017] [Indexed: 01/20/2023] Open
Abstract
Cellular therapies, such as stem cell-based treatments, have been widely researched and numerous products and treatments have been developed. Despite this, there has been relatively limited use of these technologies in the healthcare sector. This study sought to investigate the perceived barriers to this more widespread adoption. An anonymous online questionnaire was developed, based on the findings of a pilot study. This was distributed to an audience of clinicians, researchers and commercial experts in 13 countries. The results were analysed for all respondents, and also sub-grouped by geographical region, and by profession of respondents. The results of the study showed that the most significant barrier was manufacturing, with other factors such as efficacy, regulation and cost-effectiveness being identified by the different groups. This study further demonstrates the need for these important issues to be addressed during the development of cellular therapies to enable more widespread adoption of these treatments.
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Affiliation(s)
- Benjamin M Davies
- Division of Trauma and Orthopaedic Surgery, Department of Surgery, University of Cambridge, Cambridge, UK.,Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.,The UCL-Oxford Centre for the Advancement of Sustainable Medical Innovation, University of Oxford, Oxford, UK
| | - James Smith
- The UCL-Oxford Centre for the Advancement of Sustainable Medical Innovation, University of Oxford, Oxford, UK
| | - Sarah Rikabi
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Karolina Wartolowska
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Mark Morrey
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Anna French
- The UCL-Oxford Centre for the Advancement of Sustainable Medical Innovation, University of Oxford, Oxford, UK
| | - Robert MacLaren
- Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK
| | - David Williams
- Centre for Biological Engineering, The Wolfson School of Mechanical, Electrical and Manufacturing Engineering, Loughborough University, Loughborough, UK
| | - Kim Bure
- Sartorius Stedim, Göttingen, Germany
| | - Rafael Pinedo-Villanueva
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.,MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
| | - Anthony Mathur
- NIHR Cardiovascular Biomedical Research Unit, London Chest Hospital, London, UK.,Department of Cardiology, Barts Health NHS Trust, London, UK
| | - Martin Birchall
- Royal National Throat, Nose, and Ear Hospital, University College London, London, UK
| | - Evan Snyder
- Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, USA
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA
| | - Brock Reeve
- Harvard Stem Cell Institute, Cambridge, MA, USA
| | - David Brindley
- The UCL-Oxford Centre for the Advancement of Sustainable Medical Innovation, University of Oxford, Oxford, UK.,Harvard Stem Cell Institute, Cambridge, MA, USA.,Department of Paediatrics, University of Oxford, Oxford, UK.,Saïd Business School, University of Oxford, Oxford, UK.,Centre for Behavioural Medicine, UCL School of Pharmacy, University College London, London, UK
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13
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PKC in Regenerative Therapy: New Insights for Old Targets. Pharmaceuticals (Basel) 2017; 10:ph10020046. [PMID: 28524095 PMCID: PMC5490403 DOI: 10.3390/ph10020046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 05/12/2017] [Accepted: 05/16/2017] [Indexed: 01/22/2023] Open
Abstract
Effective therapies for chronic or non-healing wounds are still lacking. These tissue insults often result in severe clinical complications (i.e., infections and/or amputation) and sometimes lead to patient death. Accordingly, several research groups have focused their efforts in finding innovative and powerful therapeutic strategies to overcome these issues. On the basis of these considerations, the comprehension of the molecular cascades behind these pathological conditions could allow the identification of molecules against chronic wounds. In this context, the regulation of the Protein Kinase C (PKC) cascade has gained relevance in the prevention and/or reparation of tissue damages. This class of phosphorylating enzymes has already been considered for different physiological and pathological pathways and modulation of such enzymes may be useful in reparative processes. Herein, the recent developments in this field will be disclosed, highlighting the pivotal role of PKC α and δ in regenerative medicine. Moreover, an overview of well-established PKC ligands, acting via the modulation of these isoenzymes, will be deeply investigated. This study is aimed at re-evaluating widely known PKC modulators, currently utilized for treating other diseases, as fruitful molecules in wound-healing.
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14
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Acero L. [Internationalization, science and health: global regenerative medicine and the parallel markets]. CIENCIA & SAUDE COLETIVA 2016; 20:433-40. [PMID: 25715137 DOI: 10.1590/1413-81232015202.22272013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Accepted: 10/27/2013] [Indexed: 01/27/2023] Open
Abstract
Regenerative medicine involves a paradigm change due to organism regeneration at cellular and tissue level - a controversial contemporary issue and difficult to regulate. This article presents a summary of the main scientific, economic, social and regulatory global trends, analyzed according to relevant theoretical dilemmas in medical anthropology and in the sociology of science and health. This is especially true of the construction of a 'collective frame of reference' on the new biological and ontological entities, the shaping of biological citizenship, and governance through uncertainty. Empirical evidence is also presented on a key aspect in regulation and governance, namely the emergence of a new transnational demand in health research through the establishment of parallel markets for ova and experimental cellular therapies. Qualitative data collected for a broader research paper is analyzed, as well as journal reviews and information gathered during interviews with international leaders. The paper concludes with a discussion on the importance on international governance of clinical trials and on further exploration, towards a multilevel harmonization of a diversity of normative practices.
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Affiliation(s)
- Liliana Acero
- Programa de Pós-Graduação, Instituto de Economia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil,
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15
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Abstract
The last decade has seen considerable changes in the Regenerative Medicine industry, but unfortunately the hope for numerous treatments that ‘replace or regenerate human cells, tissues or organs to restore or establish normal function’ has not yet emerged. In contrast to this, there have been major advances in the field of cellular immunotherapy though some do not consider these to be Regenerative Medicines. Regulatory changes have in some cases improved the route to a marketing license but they have not been matched by clarification of the complex, national reimbursement processes for cell-based treatments and this has adversely affected a number of leading Regenerative Medicine Companies. The review considers the direction that the industry may go in the future in relation to scientific, manufacturing and clinical strategies which may improve the rate of success of new therapies..
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Affiliation(s)
- Paul Kemp
- HairClone, 70 Quay St, Manchester, M3 3EJ, UK
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16
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Frey BM, Zeisberger SM, Hoerstrup SP. Stem Cell Factories - the Rebirth of Tissue Engineering and Regenerative Medicine. Transfus Med Hemother 2016; 43:244-246. [PMID: 27721699 DOI: 10.1159/000448438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 07/18/2016] [Indexed: 11/19/2022] Open
Affiliation(s)
- Beat M Frey
- Blood Transfusion Service Zurich, Zurich-Schlieren, Switzerland
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17
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Jessop ZM, Al-Sabah A, Francis WR, Whitaker IS. Transforming healthcare through regenerative medicine. BMC Med 2016; 14:115. [PMID: 27510095 PMCID: PMC4980802 DOI: 10.1186/s12916-016-0669-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 08/05/2016] [Indexed: 11/10/2022] Open
Abstract
Regenerative medicine therapies, underpinned by the core principles of rejuvenation, regeneration and replacement, are shifting the paradigm in healthcare from symptomatic treatment in the 20th century to curative treatment in the 21st century. By addressing the reasons behind the rapid expansion of regenerative medicine research and presenting an overview of current clinical trials, we explore the potential of regenerative medicine to reshape modern healthcare.
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Affiliation(s)
- Zita M Jessop
- Reconstructive Surgery & Regenerative Medicine Group, Swansea University, Swansea, UK.,The Welsh Centre for Burns & Plastic Surgery, Morriston Hospital, Swansea, UK.,Institute of Life Sciences, Swansea University Medical School, Swansea University, Swansea, UK
| | - Ayesha Al-Sabah
- Reconstructive Surgery & Regenerative Medicine Group, Swansea University, Swansea, UK.,Institute of Life Sciences, Swansea University Medical School, Swansea University, Swansea, UK
| | - Wendy R Francis
- Institute of Life Sciences, Swansea University Medical School, Swansea University, Swansea, UK
| | - Iain S Whitaker
- Reconstructive Surgery & Regenerative Medicine Group, Swansea University, Swansea, UK. .,The Welsh Centre for Burns & Plastic Surgery, Morriston Hospital, Swansea, UK. .,Institute of Life Sciences, Swansea University Medical School, Swansea University, Swansea, UK.
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18
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Gurtner GC, Chapman MA. Regenerative Medicine: Charting a New Course in Wound Healing. Adv Wound Care (New Rochelle) 2016; 5:314-328. [PMID: 27366592 PMCID: PMC4900191 DOI: 10.1089/wound.2015.0663] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 07/13/2015] [Indexed: 12/13/2022] Open
Abstract
Significance: Chronic wounds are a prevalent and costly problem in the United States. Improved treatments are needed to heal these wounds and prevent serious complications such as infection and amputation. Recent Advances: In wound healing, as in other areas of medicine, technologies that have the potential to regenerate as opposed to repair tissue are gaining ground. These include customizable nanofiber matrices incorporating novel materials; a variety of autologous and allogeneic cell types at various stages of differentiation (e.g., pluripotent, terminally differentiated); peptides; proteins; small molecules; RNA inhibitors; and gene therapies. Critical Issues: Wound healing is a logical target for regenerative medicine due to the accessibility and structure of skin, the regenerative nature of healing, the lack of good limb salvage treatments, and the current use of cell therapies. However, more extensive knowledge of pathophysiologic targets is needed to inform regenerative strategies, and new technologies must demonstrate value in terms of outcomes and related health economic measures to achieve successful market access and penetration. Future Directions: Due to similarities in cell pathways and developmental mechanisms, regenerative technologies developed in one therapeutic area may be applicable to others. Approaches that proceed from human genomic or other big data sources to models are becoming increasingly common and will likely suggest novel therapeutic avenues. To fully capitalize on the advances in regenerative medicine, studies must demonstrate the value of new therapies in identified patient populations, and sponsors must work with regulatory agencies to develop appropriate dossiers supporting timely approval.
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19
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Hart LR, Li S, Sturgess C, Wildman R, Jones JR, Hayes W. 3D Printing of Biocompatible Supramolecular Polymers and their Composites. ACS APPLIED MATERIALS & INTERFACES 2016; 8:3115-3122. [PMID: 26766139 DOI: 10.1021/acsami.5b10471] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
A series of polymers capable of self-assembling into infinite networks via supramolecular interactions have been designed, synthesized, and characterized for use in 3D printing applications. The biocompatible polymers and their composites with silica nanoparticles were successfully utilized to deposit both simple cubic structures, as well as a more complex twisted pyramidal feature. The polymers were found to be not toxic to a chondrogenic cell line, according to ISO 10993-5 and 10993-12 standard tests and the cells attached to the supramolecular polymers as demonstrated by confocal microscopy. Silica nanoparticles were then dispersed within the polymer matrix, yielding a composite material which was optimized for inkjet printing. The hybrid material showed promise in preliminary tests to facilitate the 3D deposition of a more complex structure.
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Affiliation(s)
- Lewis R Hart
- Department of Chemistry, University of Reading , Whiteknights, Reading, RG6 6AD, U.K
| | - Siwei Li
- Department of Materials, Imperial College London , South Kensington Campus, London, SW7 2BP, U.K
| | - Craig Sturgess
- Department of Chemical and Environmental Engineering, The University of Nottingham , University Park, Nottingham, NG7 2RD, U.K
| | - Ricky Wildman
- Department of Chemical and Environmental Engineering, The University of Nottingham , University Park, Nottingham, NG7 2RD, U.K
| | - Julian R Jones
- Department of Materials, Imperial College London , South Kensington Campus, London, SW7 2BP, U.K
| | - Wayne Hayes
- Department of Chemistry, University of Reading , Whiteknights, Reading, RG6 6AD, U.K
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20
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Swioklo S, Constantinescu A, Connon CJ. Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells. Stem Cells Transl Med 2016; 5:339-49. [PMID: 26826163 DOI: 10.5966/sctm.2015-0131] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 12/16/2015] [Indexed: 12/16/2022] Open
Abstract
Despite considerable progress within the cell therapy industry, unmet bioprocessing and logistical challenges associated with the storage and distribution of cells between sites of manufacture and the clinic exist. We examined whether hypothermic (4°C-23°C) preservation of human adipose-derived stem cells could be improved through their encapsulation in 1.2% calcium alginate. Alginate encapsulation improved the recovery of viable cells after 72 hours of storage. Viable cell recovery was highly temperature-dependent, with an optimum temperature of 15°C. At this temperature, alginate encapsulation preserved the ability for recovered cells to attach to tissue culture plastic on rewarming, further increasing its effect on total cell recovery. On attachment, the cells were phenotypically normal, displayed normal growth kinetics, and maintained their capacity for trilineage differentiation. The number of cells encapsulated (up to 2 × 10(6) cells per milliliter) did not affect viable cell recovery nor did storage of encapsulated cells in a xeno-free, serum-free,current Good Manufacturing Practice-grade medium. We present a simple, low-cost system capable of enhancing the preservation of human adipose-derived stem cells stored at hypothermic temperatures, while maintaining their normal function. The storage of cells in this manner has great potential for extending the time windows for quality assurance and efficacy testing, distribution between the sites of manufacture and the clinic, and reducing the wastage associated with the limited shelf life of cells stored in their liquid state.
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Affiliation(s)
- Stephen Swioklo
- Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Andrei Constantinescu
- Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Che J Connon
- Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom
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21
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Rafiq QA, Ortega I, Jenkins SI, Wilson SL, Patel AK, Barnes AL, Adams CF, Delcassian D, Smith D. The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products. Regen Med 2015; 10:989-1003. [PMID: 26628407 DOI: 10.2217/rme.15.56] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.
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Affiliation(s)
- Qasim A Rafiq
- Centre for Biological Engineering, Wolfson School of Mechanical & Manufacturing Engineering, Loughborough University, Leicestershire, LE11 3TU, UK.,Aston Medical Research Institute, School of Life & Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK
| | - Ilida Ortega
- Bioengineering & Health Technologies Group, The School of Clinical Dentistry, University of Sheffield, S10 2TA, UK
| | - Stuart I Jenkins
- Institute for Science & Technology in Medicine, Keele University, Staffordshire, ST5 5BG, UK
| | - Samantha L Wilson
- Academic Ophthalmology, Division of Clincial Neuroscience, Queen's Medical Centre Campus, University of Nottingham, NG7 2UH, UK
| | - Asha K Patel
- Wolfson Centre for Stem Cells, Tissue Engineering & Modeling, University of Nottingham, Nottingham, NG7 2RD, UK.,David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | | | - Christopher F Adams
- Institute for Science & Technology in Medicine, Keele University, Staffordshire, ST5 5BG, UK
| | - Derfogail Delcassian
- Department of Materials, Imperial College London, Exhibition Road, London SW7 2AZ, UK.,Wolfson Centre for Stem Cells, Centre for Biological Sciences, School of Pharmacy, University of Nottingham, NG7 2RD, UK
| | - David Smith
- Centre for Biological Engineering, Wolfson School of Mechanical & Manufacturing Engineering, Loughborough University, Leicestershire, LE11 3TU, UK.,PCT, a Caladrius company, 4 Pearl Court, Suite C, Allendale, NJ 07401, USA
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22
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Londono R, Badylak SF. Regenerative Medicine Strategies for Esophageal Repair. TISSUE ENGINEERING PART B-REVIEWS 2015; 21:393-410. [PMID: 25813694 DOI: 10.1089/ten.teb.2015.0014] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside.
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Affiliation(s)
- Ricardo Londono
- 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Stephen F Badylak
- 1 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,4 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania
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23
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Kaul H, Ventikos Y. On the genealogy of tissue engineering and regenerative medicine. TISSUE ENGINEERING. PART B, REVIEWS 2015; 21:203-17. [PMID: 25343302 PMCID: PMC4390213 DOI: 10.1089/ten.teb.2014.0285] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed.
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Affiliation(s)
- Himanshu Kaul
- Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom
| | - Yiannis Ventikos
- Department of Mechanical Engineering, University College London, London, United Kingdom
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24
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Fang YL, Chen XG, W T G. Gene delivery in tissue engineering and regenerative medicine. J Biomed Mater Res B Appl Biomater 2014; 103:1679-99. [PMID: 25557560 DOI: 10.1002/jbm.b.33354] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 11/07/2014] [Accepted: 11/18/2014] [Indexed: 12/13/2022]
Abstract
As a promising strategy to aid or replace tissue/organ transplantation, gene delivery has been used for regenerative medicine applications to create or restore normal function at the cell and tissue levels. Gene delivery has been successfully performed ex vivo and in vivo in these applications. Excellent proliferation capabilities and differentiation potentials render certain cells as excellent candidates for ex vivo gene delivery for regenerative medicine applications, which is why multipotent and pluripotent cells have been intensely studied in this vein. In this review, gene delivery is discussed in detail, along with its applications to tissue engineering and regenerative medicine. A definition of a stem cell is compared to a definition of a stem property, and both provide the foundation for an in-depth look at gene delivery investigations from a germ lineage angle.
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Affiliation(s)
- Y L Fang
- Department of Chemical & Biomolecular Engineering, Laboratory for Gene Therapy and Cellular Engineering, Tulane University, 300 Lindy Boggs Center, New Orleans, Louisiana, 70118
| | - X G Chen
- Department of Chemical & Biomolecular Engineering, Laboratory for Gene Therapy and Cellular Engineering, Tulane University, 300 Lindy Boggs Center, New Orleans, Louisiana, 70118
| | - Godbey W T
- Department of Chemical & Biomolecular Engineering, Laboratory for Gene Therapy and Cellular Engineering, Tulane University, 300 Lindy Boggs Center, New Orleans, Louisiana, 70118
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25
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Davies BM, Rikabi S, French A, Pinedo-Villanueva R, Morrey ME, Wartolowska K, Judge A, MacLaren RE, Mathur A, Williams DJ, Wall I, Birchall M, Reeve B, Atala A, Barker RW, Cui Z, Furniss D, Bure K, Snyder EY, Karp JM, Price A, Carr A, Brindley DA. Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study. J Tissue Eng 2014; 5:2041731414551764. [PMID: 25383173 PMCID: PMC4221931 DOI: 10.1177/2041731414551764] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 07/20/2014] [Indexed: 01/08/2023] Open
Abstract
There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.
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Affiliation(s)
- Benjamin M Davies
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Sarah Rikabi
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Anna French
- The Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation (CASMI), University of Oxford, Oxford, UK
| | - Rafael Pinedo-Villanueva
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK ; MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, UK
| | - Mark E Morrey
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Karolina Wartolowska
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Andrew Judge
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK ; MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, UK
| | - Robert E MacLaren
- Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK
| | - Anthony Mathur
- NIHR Cardiovascular Biomedical Research Unit, London Chest Hospital, London, UK ; Department of Cardiology, Barts Health NHS Trust, London, UK ; Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK
| | - David J Williams
- Centre for Biological Engineering, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, UK
| | - Ivan Wall
- Department of Biochemical Engineering, University College London, London, UK ; Department of Nanobiomedical Science & BK21 Plus NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea ; Biomaterials and Tissue Engineering Lab, Department of Nanobiomedical Science and WCU Research Center, Dankook University, Cheonan, Republic of Korea
| | | | - Brock Reeve
- Harvard Stem Cell Institute, Cambridge, MA, USA
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Richard W Barker
- The Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation (CASMI), University of Oxford, Oxford, UK
| | - Zhanfeng Cui
- Oxford Centre for Tissue Engineering and Bioprocessing, University of Oxford, Oxford, UK
| | - Dominic Furniss
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Kim Bure
- Sartorius Stedim, Göttingen, Germany
| | - Evan Y Snyder
- Sanford-Burnham Medical Research Institute, La Jolla, CA, USA ; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA ; Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA
| | - Jeffrey M Karp
- Harvard Stem Cell Institute, Cambridge, MA, USA ; Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA ; Harvard Medical School, Cambridge, MA, USA
| | - Andrew Price
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Andrew Carr
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK ; The Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation (CASMI), University of Oxford, Oxford, UK
| | - David A Brindley
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK ; The Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation (CASMI), University of Oxford, Oxford, UK ; Harvard Stem Cell Institute, Cambridge, MA, USA ; Centre for Behavioural Medicine, UCL School of Pharmacy, University College London, London, UK
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26
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Bayon Y, Vertès AA, Ronfard V, Egloff M, Snykers S, Salinas GF, Thomas R, Girling A, Lilford R, Clermont G, Kemp P. Translating cell-based regenerative medicines from research to successful products: challenges and solutions. TISSUE ENGINEERING PART B-REVIEWS 2014; 20:246-56. [PMID: 24754565 DOI: 10.1089/ten.teb.2013.0727] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The Tissue Engineering & Regenerative Medicine International Society-Europe (TERMIS-EU) Industry Committee as well as its TERMIS-Americas (AM) counterpart intend to address the specific challenges and needs facing the industry in translating academic research into commercial products. Over the last 3 years, the TERMIS-EU Industry Committee has worked with commercial bodies to deliver programs that encourage academics to liaise with industry in proactive collaborations. The TERMIS-EU 2013 Industry Symposium aimed to build on this commercial agenda by focusing on two topics: Operations Management (How to move a process into the good manufacturing practice [GMP] environment) and Clinical Translation (Moving a GMP process into robust trials). These topics were introduced by providing the synergistic business perspective of partnering between the multiple regenerative medicine stakeholders, throughout the life cycle of product development. Seven industry leaders were invited to share their experience, expertise, and strategies. Due to the complex nature of regenerative medicine products, partnering for their successful commercial development seems inevitable to overcome all obstacles by sharing experiences and expertise of all stakeholders. When ideally implemented, the "innovation quotient" of a virtual team resulting from the combination of internal and external project teams can be maximized through maximizing the three main dimensions: core competences, technology portfolio, and alliance management.
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Affiliation(s)
- Yves Bayon
- 1 Covidien-Sofradim Production , Trévoux, France
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27
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Turner NJ, Keane TJ, Badylak SF. Lessons from developmental biology for regenerative medicine. ACTA ACUST UNITED AC 2013; 99:149-59. [DOI: 10.1002/bdrc.21040] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 07/27/2013] [Accepted: 07/27/2013] [Indexed: 12/17/2022]
Affiliation(s)
- Neill J. Turner
- McGowan Institute for Regenerative Medicine; University of Pittsburgh, Pittsburgh, Pennsylvania and Department of Surgery, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Timothy J. Keane
- McGowan Institute for Regenerative Medicine; University of Pittsburgh, Pittsburgh, Pennsylvania and Department of Bioengineering, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Stephen F. Badylak
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, and Department of Bioengineering, University of Pittsburgh; Pittsburgh Pennsylvania
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28
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29
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Horch RE, Popescu LM, Polykandriotis E. History of Regenerative Medicine. Regen Med 2013. [DOI: 10.1007/978-94-007-5690-8_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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30
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Slingerland AS, Smits AIPM, Bouten CVC. Then and now: hypes and hopes of regenerative medicine. Trends Biotechnol 2012; 31:121-3. [PMID: 23280408 DOI: 10.1016/j.tibtech.2012.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Accepted: 12/03/2012] [Indexed: 11/15/2022]
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31
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Totonelli G, Maghsoudlou P, Fishman JM, Orlando G, Ansari T, Sibbons P, Birchall MA, Pierro A, Eaton S, De Coppi P. Esophageal tissue engineering: A new approach for esophageal replacement. World J Gastroenterol 2012; 18:6900-7. [PMID: 23322987 PMCID: PMC3531673 DOI: 10.3748/wjg.v18.i47.6900] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Revised: 06/14/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly sug- gest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed.
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Orlando G, Wood KJ, De Coppi P, Baptista PM, Binder KW, Bitar KN, Breuer C, Burnett L, Christ G, Farney A, Figliuzzi M, Holmes JH, Koch K, Macchiarini P, Mirmalek Sani SH, Opara E, Remuzzi A, Rogers J, Saul JM, Seliktar D, Shapira-Schweitzer K, Smith T, Solomon D, Van Dyke M, Yoo JJ, Zhang Y, Atala A, Stratta RJ, Soker S. Regenerative medicine as applied to general surgery. Ann Surg 2012; 255:867-80. [PMID: 22330032 PMCID: PMC3327776 DOI: 10.1097/sla.0b013e318243a4db] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues, or organs to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues, and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate.
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Affiliation(s)
- Giuseppe Orlando
- Wake Forest Institute for Regenerative Medicine, Winston Salem, NC, USA.
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Promissory futures and possible pasts: The dynamics of contemporary expectations in regenerative medicine. BIOSOCIETIES 2012. [DOI: 10.1057/biosoc.2011.24] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Totonelli G, Maghsoudlou P, Garriboli M, Riegler J, Orlando G, Burns AJ, Sebire NJ, Smith VV, Fishman JM, Ghionzoli M, Turmaine M, Birchall MA, Atala A, Soker S, Lythgoe MF, Seifalian A, Pierro A, Eaton S, De Coppi P. A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration. Biomaterials 2012; 33:3401-10. [PMID: 22305104 PMCID: PMC4022101 DOI: 10.1016/j.biomaterials.2012.01.012] [Citation(s) in RCA: 148] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Accepted: 01/05/2012] [Indexed: 12/20/2022]
Abstract
Management of intestinal failure remains a clinical challenge and total parenteral nutrition, intestinal elongation and/or transplantation are partial solutions. In this study, using a detergent-enzymatic treatment (DET), we optimize in rats a new protocol that creates a natural intestinal scaffold, as a base for developing functional intestinal tissue. After 1 cycle of DET, histological examination and SEM and TEM analyses showed removal of cellular elements with preservation of the native architecture and connective tissue components. Maintenance of biomechanical, adhesion and angiogenic properties were also demonstrated strengthen the idea that matrices obtained using DET may represent a valid support for intestinal regeneration.
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Affiliation(s)
- Giorgia Totonelli
- Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, London WC1N 1EH, UK
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Crawford B, Koshy ST, Jhamb G, Woodford C, Thompson CM, Levy AS, Rush JWE, Guillemette JG, Lillicrap D, Jervis E. Cardiac decellularisation with long-term storage and repopulation with canine peripheral blood progenitor cells. CAN J CHEM ENG 2011. [DOI: 10.1002/cjce.20670] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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36
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Abstract
This overview traces the history of regenerative medicine pertinent to organ transplantation, illustrates potential clinical applications reported to date, and highlights progress achieved in the field of complex modular organ engineering. Regenerative medicine can now produce relatively simple tissues such as skin, bladders, vessels, urethras, and upper airways, whereas engineering or generation of complex modular organs remains a major challenge. Ex vivo organ engineering may benefit from complementary investigations in the fields of developmental biology and stem cells and transplantation before its full potential can be realized.
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Hodgkinson T, Bayat A. Dermal substitute-assisted healing: enhancing stem cell therapy with novel biomaterial design. Arch Dermatol Res 2011; 303:301-15. [PMID: 21365208 DOI: 10.1007/s00403-011-1131-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2010] [Revised: 01/12/2011] [Accepted: 01/21/2011] [Indexed: 12/17/2022]
Abstract
The use of dermal substitutes is increasingly widespread but the outcomes of substitute-assisted healing remain functionally deficient. Presently, the most successful scaffolds are acellular polymer matrices, prepared through lyophilization and phase separation techniques, designed to mimic the dermal extracellular matrix. The application of scaffolds containing viable cells has proven to be problematic due to short shelf-life, high cost and death of transplanted cells as a result of immune rejection and apoptosis. Recent advances in biomaterial science have made new techniques available capable of increasing scaffold complexity, allowing the creation of 3D microenvironments that actively control cell behaviour. Importantly, it may be possible through these sophisticated novel techniques, including bio-printing and electrospinning, to accurately direct stem cell behaviour. This complex proposal involves the incorporation of cell-matrix, cell-cell, mechanical cues and soluble factors delivered in a spatially and temporally pertinent manner. This requires accurate modelling of three-dimensional stem cell interactions within niche environments to identify key signalling molecules and mechanisms. The application of stem cells within substitutes containing such environments may result in greatly improved transplanted cell viability. Ultimately this may increase cellular organization and complexity of skin substitutes. This review discusses progress made in improving the efficacy of cellular dermal substitutes for the treatment of cutaneous defects and the potential of evolving new technology to improve current results.
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Affiliation(s)
- T Hodgkinson
- Plastic and Reconstructive Surgery Research, Manchester Interdisciplinary Biocentre, University of Manchester, UK
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Polykandriotis E, Popescu LM, Horch RE. Regenerative medicine: then and now--an update of recent history into future possibilities. J Cell Mol Med 2011; 14:2350-8. [PMID: 20825521 PMCID: PMC3823153 DOI: 10.1111/j.1582-4934.2010.01169.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
The fields of tissue engineering (TE) and regenerative medicine (RegMed) are yet to bring about the anticipated therapeutic revolution. After two decades of extremely high expectations and often disappointing returns both in the medical as well as in the financial arena, this scientific field reflects the sense of a new era and suggests the feeling of making a fresh start although many scientists are probably seeking reorientation. Much of research was industry driven, so that especially in the aftermath of the recent financial meltdown in the last 2 years we have witnessed a biotech asset yard sale. Despite any monetary shortcomings, from a technological point of view there have been great leaps that are yet to find their way to the patient. RegMed is definitely bound to play a major role in our life because it embodies one of the primordial dreams of mankind, such as: everlasting youth, flying, remote communication and setting foot on the moon. The Journal of Cellular and Molecular Medicine has been at the frontier of these developments in TE and RegMed from its beginning and reflects recent scientific advances in both fields. Therefore this review tries to look at RegMed through the keyhole of history which might just be like looking ‘back to the future’.
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Affiliation(s)
- E Polykandriotis
- Department of Plastic and Hand Surgery and Laboratory for Tissue Engineering and Regenerative Medicine, University of Erlangen, Erlangen, Germany
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Affiliation(s)
- Chris Mason
- Advanced Centre for Biochemical Engineering, University College London, Roberts Building, Torrington Place, London, WC1E 7JE, UK
| | - Elisa Manzotti
- Future Medicine Ltd, Unitec House, 2 Albert Place, Finchley Central, London, N3 1QB, UK
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Mason C, Manzotti E. Regenerative medicine cell therapies: numbers of units manufactured and patients treated between 1988 and 2010. Regen Med 2010; 5:307-13. [DOI: 10.2217/rme.10.37] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Chris Mason
- Advanced Centre for Biochemical Engineering, University College London, Roberts Building, Torrington Place, London, WC1E 7JE, UK
| | - Elisa Manzotti
- Future Medicine Ltd, Unitec House, 2 Albert Place, Finchley Central, London, N3 1QB, UK
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Ginty PJ, Singh PB, Smith D, Hourd P, Williams DJ. Achieving reimbursement for regenerative medicine products in the USA. Regen Med 2010; 5:463-9. [DOI: 10.2217/rme.10.13] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Achieving reimbursement for regenerative medicine products is potentially a greater challenge than gaining US FDA approval, making it a decisive factor in the success or failure of small businesses. However, the mechanisms by which reimbursement is achieved are still seen as something of a ‘black box’, especially to those outside of the USA. This report aims to provide insights into the mechanisms of reimbursement and variety of payers in the USA, and to act as a starting point for a successful US reimbursement strategy. Fundamental concepts such as coverage, payment and coding are explained and linked with the factors that potentially determine the successful reimbursement of regenerative medicine products, including cost of goods and clinical study design. Finally, important considerations for the design of clinical studies that satisfy both the payers and the FDA are discussed and the key elements of a successful company strategy identified.
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Affiliation(s)
| | - PB Singh
- Centre for Biological Engineering, Loughborough University, Loughborough, LE11 3TU, UK
| | - D Smith
- Pepper Hamilton Law LLP, Pittsburgh, PA 15219-2502, USA
| | - P Hourd
- Centre for Biological Engineering, Loughborough University, Loughborough, LE11 3TU, UK
| | - DJ Williams
- Centre for Biological Engineering, Loughborough University, Loughborough, LE11 3TU, UK
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Brindley D, Davie N. Regenerative medicine through a crisis: social perception and the financial reality. Rejuvenation Res 2010; 12:455-61. [PMID: 20041739 DOI: 10.1089/rej.2009.0981] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The aim of this perspective piece is to highlight how the "social perception" and "financial reality" of regenerative medicine may act to hinder its evolution into the principal health-care option for the future. We also consider the role of the consumer and the need for increased public awareness. Furthermore, we consider the effects of the changing social attitudes toward the field, as well as taking into account the influence of current and future political thinking. From a financial viewpoint, we analyze the compatibility of the current venture capital model with regenerative medicine start-ups and explore approaches to ensure sufficient funding and support throughout all stages of product development, for example, the modularization of funding.
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Affiliation(s)
- David Brindley
- Department of Biochemical Engineering University College London, Torrington Place, London, WC1E 7JE, United Kingdom
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Mason C, Manzotti E. Regen: the industry responsible for cell-based therapies. Regen Med 2009; 4:783-5. [DOI: 10.2217/rme.09.72] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Chris Mason
- Advanced Centre for Biochemical Engineering, University College London, Roberts Building, Torrington Place, London, WC1E 7JE, UK
| | - Elisa Manzotti
- Future Medicine Ltd, Unitec House, 2 Albert Place, Finchley Central, London, N3 1QB, UK
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Plagnol AC, Rowley E, Martin P, Livesey F. Industry perceptions of barriers to commercialization of regenerative medicine products in the UK. Regen Med 2009; 4:549-59. [PMID: 19580404 DOI: 10.2217/rme.09.21] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
AIMS Regenerative medicine is an emerging field with the potential to provide widespread improvement in healthcare and patient wellbeing via the delivery of therapies that can restore, regenerate or repair damaged tissue. As an industry, it could significantly contribute to economic growth if products are successfully commercialized. However, to date, relatively few products have reached the market owing to a variety of barriers, including a lack of funding and regulatory hurdles. The present study analyzes industry perceptions of the barriers to commercialization that currently impede the success of the regenerative medicine industry in the UK. MATERIALS & METHODS The analysis is based on 20 interviews with leading industrialists in the field. RESULTS The study revealed that scientific research in regenerative medicine is thriving in the UK. Unfortunately, lack of access to capital, regulatory hurdles, lack of clinical evidence leading to problems with reimbursement, as well as the culture of the NHS do not provide a good environment for the commercialization of regenerative medicine products. CONCLUSION Policy interventions, including increased translational government funding, a change in NHS and NICE organization and policies, and regulatory clarity, would likely improve the general outcomes for the regenerative medicine industry in the UK.
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Affiliation(s)
- Anke C Plagnol
- Faculty of Politics, Psychology, Sociology & International Studies, University of Cambridge, Cambridge, CB2 3RQ, UK
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Mason C, Dunnill P. The strong financial case for regenerative medicine and the regen industry. Regen Med 2008; 3:351-63. [PMID: 18462058 DOI: 10.2217/17460751.3.3.351] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Although the therapeutic promise of regenerative medicine is immensely exciting, the cost of product development, and particularly of clinical trials, for the more demanding applications will be high. For this reason it is vital for scientists and start-ups who wish to see their ideas implemented to be able to convince established major pharmaceutical or device companies with the necessary 'deep pockets' that the expenditure can yield an appropriate return. It also means that governments and health insurance companies must see a gain in funding regenerative medicine for patients. To address this issue the costs of five major medical conditions that could benefit from regenerative medicine have been defined for the USA as an illustration. This choice of country was made as potentially the largest initial market and one where the billing system for healthcare allows access to individual direct and some indirect costs. The data are complemented by a number of relevant examples of costs per quality-adjusted life year to indicate where current treatment methods are weak or strong. Finally, the relationship of the nascent regen* industry to the pharma and medical device sectors is summarized to assess the challenge of encouraging their involvement.
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Affiliation(s)
- Chris Mason
- Advanced Centre for Biochemical Engineering, University College London, London, WCIE 7JE, UK.
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48
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Singh P, Williams DJ. Cell therapies: realizing the potential of this new dimension to medical therapeutics. J Tissue Eng Regen Med 2008; 2:307-19. [DOI: 10.1002/term.108] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Mason C, Dunnill P. Lessons for the nascent regenerative medicine industry from the biotech sector. Regen Med 2007; 2:753-6. [PMID: 17907927 DOI: 10.2217/17460751.2.5.753] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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