|
1
|
Lee SSJ, Caruncho M, Chung WK, Johnston J, Tabb K, Appelbaum PS. Individualized interventions for rare genetic conditions and the research-treatment spectrum: Stakeholder perspectives. Genet Med 2023; 25:100832. [PMID: 36964709 PMCID: PMC10258687 DOI: 10.1016/j.gim.2023.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 03/20/2023] [Accepted: 03/20/2023] [Indexed: 03/26/2023] Open
Abstract
PURPOSE Advances in the study of ultrarare genetic conditions are leading to the development of targeted interventions developed for single or very small numbers of patients. Owing to the experimental but also highly individualized nature of these interventions, they are difficult to classify cleanly as either research or clinical care. Our goal was to understand how parents, institutional review board members, and clinical geneticists familiar with individualized genetic interventions conceptualize these activities and their implications for the relationship between research and clinical care. METHODS We conducted qualitative, semi-structured interviews with 28 parents, institutional review board members, and clinical geneticists and derived themes from those interviews through content analysis. RESULTS Individuals described individualized interventions as blurring the lines between research and clinical care and focused on hopes for therapeutic benefit and expectations for generalizability of knowledge and benefit to future patients. CONCLUSION Individualized interventions aimed at one or few patients reveal the limitations of a binary framing of research and clinical care. As a hybrid set of activities, individualized interventions suggest the need for flexibility and new frameworks that acknowledge these activities across the spectrum of research and clinical care.
Collapse
Affiliation(s)
- Sandra Soo-Jin Lee
- Division of Ethics, Department of Medical Humanities and Ethics, Columbia University, New York, NY.
| | - Mikaella Caruncho
- Division of Ethics, Department of Medical Humanities and Ethics, Columbia University, New York, NY
| | - Wendy K Chung
- Departments of Pediatrics and Medicine, Columbia University, New York, NY
| | | | - Kathryn Tabb
- Department of Philosophy, Bard College, Annandale-on-Hudson, NY
| | - Paul S Appelbaum
- Department of Psychiatry and New York State Psychiatric Institute, Columbia University, New York, NY
| |
Collapse
|
|
2
|
Qiu T, Pochopień M, Hanna E, Liang S, Wang Y, Han R, Toumi M, Aballéa S. Challenges in the market access of regenerative medicines, and implications for manufacturers and decision-makers: a systematic review. Regen Med 2022; 17:119-139. [PMID: 35042424 DOI: 10.2217/rme-2021-0083] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Aim: Regenerative medicines (RMs) are expected to transform the treatment paradigm of rare, life-threatening diseases, while substantial challenges impede its market access. This study aimed to present these challenges. Materials & methods: Publications identified in the Medline and Embase databases until December 2020 were included. Results: Uncertainties around the relative effectiveness and long-term benefits of RMs are most scrutinized. A new reference case for RMs is questionable, but examining impacts of study perspective, time horizon, discount rate and extrapolation methods on estimates is advised. Establishing reasonable prices of RMs requires increased transparency in the development costs and better values measurements. Outcome-based payments require considerable investments and potential legislative adjustments. Conclusion: Greater flexibility for health technology assessment and economic analyses of RMs is necessary. This comprehensive review may prompt more multi-stakeholder conversations to discuss the optimized strategy for value assessment, pricing and payment in order to accelerate the market access of RMs.
Collapse
Affiliation(s)
- Tingting Qiu
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France
| | - Michał Pochopień
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.,Creativ-Ceutical, 215, Rue du Faubourg St-Honoré, 75008, Paris, France
| | - Eve Hanna
- Creativ-Ceutical, 215, Rue du Faubourg St-Honoré, 75008, Paris, France
| | - Shuyao Liang
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France
| | - Yitong Wang
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France
| | - Ru Han
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France
| | - Mondher Toumi
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France
| | - Samuel Aballéa
- Creativ-Ceutical, 215, Rue du Faubourg St-Honoré, 75008, Paris, France
| |
Collapse
|
|
3
|
Muqier M, Xiao H, Yu X, Li Y, Bao M, Bao Q, Han S, Baigude H. Synthesis of PEGylated cationic curdlan derivatives with enhanced biocompatibility. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2021; 33:465-480. [PMID: 34641765 DOI: 10.1080/09205063.2021.1992589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Cationic polysaccharides have shown excellent ability of nucleic acids delivery. However, cationic curdlan derivatives with high degree of amination cause damage to the cell membrane and induce considerable cytotoxicity, limiting their in vivo application. Herein, we synthesized PEGylated 6-amino-6-deoxy-curdlan derivatives containing cleavable disulfide bonds. The resulting polymers (denote 6AC-2S PEGx) not only showed high affinity to siRNA but also exhibited significantly decreased cytotoxicity and hemolysis effect, while showing remarkable in vitro transfection efficiency. In vivo study demonstrated that 6AC-2S PEG40, which had a lower LD50 value than that of 6AC-100, did not cause liver damage, as the i.v. injection of 6AC-2S PEG40 to mouse did not increase serum level of ALT/AST. Furthermore, tissue distribution results showed that 6AC-2S PEG40 successfully delivered siRNA to liver, lung and spleen. Collectively, our data confirmed that PEGylation can increase the biocompatibility of cationic curdlan derivatives, which is a promising carrier for nucleic acid therapeutics.
Collapse
Affiliation(s)
- Muqier Muqier
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| | - Hai Xiao
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| | - Xiang Yu
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| | - Yifeng Li
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| | - Mingming Bao
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| | - Qingming Bao
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| | - Shuqin Han
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| | - Huricha Baigude
- Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, P.R. China
| |
Collapse
|
|
4
|
Qiu T, Wang Y, Liang S, Han R, Toumi M. Partnership agreements for regenerative medicines: a database analysis and implications for future innovation. Regen Med 2021; 16:733-755. [PMID: 34431716 DOI: 10.2217/rme-2021-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: Partnerships have been leveraged to advance the regenerative medicines (RMs) development. This study analyzed the evolution of partnership landscape for regenerative medicines (RMs). Methods: Partnership agreements publicly announced from January 2014 - June 2020 were described. Results: 1169 partnership agreements with total amount of US$63,496 million were identified. Most agreements concerned RMs that were for oncology (25.3%), in the discovery or preclinical phase (66.9%) and gene-based products (45.3%). The most common partnership type is collaborative agreements without licensing. The partnerships between 'biotechnology companies and not-for-profit organizations' represented the largest number (n = 416; 35.6%). 'Big Pharma' preferred collaboration and licensing agreements with a higher amount. Conclusion: Collaborations between highly specialized players with complementary expertise promote the successful translation of scientific discovery to RMs.
Collapse
Affiliation(s)
- Tingting Qiu
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, Marseille, 13385, France
| | - Yitong Wang
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, Marseille, 13385, France
| | - Shuyao Liang
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, Marseille, 13385, France
| | - Ru Han
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, Marseille, 13385, France
| | - Mondher Toumi
- Department of Public Health, Aix-Marseille University, 27 Boulevard Jean Moulin, Marseille, 13385, France
| |
Collapse
|
|
5
|
García-González J, Marhuenda-Castillo S, Romero-Carretero S, Beltrán-García J. New era of personalized medicine: Advanced therapy medicinal products in Europe. World J Immunol 2021; 11:1-10. [DOI: 10.5411/wji.v11.i1.1] [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: 01/14/2021] [Revised: 02/24/2021] [Accepted: 06/07/2021] [Indexed: 02/06/2023] Open
Abstract
Advanced therapy medicinal products are human medical therapies based on genes, cells, or tissues, and due to their characteristics, they offer new innovative opportunities for the treatment of diseases and injuries, especially for diseases beyond the reach of traditional approaches. These therapies are at the forefront of innovation and have historically been very controversial, although in the last decade they have gained prominence while the number of new advanced therapies has increased every year. In this regard, despite the controversy they may generate, they are expected to dominate the market in the coming decades. Technologies based on advanced therapies are the present and future of medicine and bring us closer to the long-awaited precision medicine. Here we review the field as it stands today, with a focus on the molecular mechanisms that guided the different advanced therapies approved by the European Medicines Agency, their current status, and their legal approval.
Collapse
Affiliation(s)
| | | | | | - Jesús Beltrán-García
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, Valencia 46010, Spain
- Center for Biomedical Research in Rare Diseases Network (CIBERER), Carlos III Health Institute, Valencia 46010, Spain
- INCLIVA Institute of Sanitary Research, Valencia 46010, Spain
| |
Collapse
|
|
6
|
The impact of COVID-19 on the cell and gene therapies industry: Disruptions, opportunities, and future prospects. Drug Discov Today 2021; 26:2269-2281. [PMID: 33892148 PMCID: PMC8057929 DOI: 10.1016/j.drudis.2021.04.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/20/2021] [Accepted: 04/13/2021] [Indexed: 12/26/2022]
Abstract
Coronavirus 2019 (COVID-19) has caused significant disruption to the cell and gene therapy (CGT) industry, which has historically faced substantial complexities in supply of materials, and manufacturing and logistics processes. As decision-makers shifted their priorities to COVID-19-related issues, the challenges in market authorisation, and price and reimbursement of CGTs were amplified. Nevertheless, it is encouraging to see that some CGT developers are adapting their efforts toward the development of promising COVID-19-related therapeutics and vaccines. Manufacturing resilience, digitalisation, telemedicine, value-based pricing, and innovative payment mechanisms will be increasingly harnessed to ensure that market access of CGTs is not severely disrupted.
Collapse
|
|
7
|
Angrist M, Yang A, Kantor B, Chiba-Falek O. Good problems to have? Policy and societal implications of a disease-modifying therapy for presymptomatic late-onset Alzheimer's disease. LIFE SCIENCES, SOCIETY AND POLICY 2020; 16:11. [PMID: 33043412 PMCID: PMC7548124 DOI: 10.1186/s40504-020-00106-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/09/2020] [Indexed: 06/11/2023]
Abstract
In the United States alone, the prevalence of AD is expected to more than double from six million people in 2019 to nearly 14 million people in 2050. Meanwhile, the track record for developing treatments for AD has been marked by decades of failure. But recent progress in genetics, neuroscience and gene editing suggest that effective treatments could be on the horizon. The arrival of such treatments would have profound implications for the way we diagnose, triage, study, and allocate resources to Alzheimer's patients. Because the disease is not rare and because it strikes late in life, the development of therapies that are expensive and efficacious but less than cures, will pose particular challenges to healthcare infrastructure. We have a window of time during which we can begin to anticipate just, equitable and salutary ways to accommodate a disease-modifying therapy Alzheimer's disease. Here we consider the implications for caregivers, clinicians, researchers, and the US healthcare system of the availability of an expensive, presymptomatic treatment for a common late-onset neurodegenerative disease for which diagnosis can be difficult.
Collapse
Affiliation(s)
- Misha Angrist
- Initiative for Science and Society and Social Science Research Institute, Duke University, Durham, North Carolina 27708-0222 USA
| | | | - Boris Kantor
- Duke University Department of Neurobiology, Durham, North Carolina 27710-3209 USA
| | - Ornit Chiba-Falek
- Duke University Department of Neurology, 311 Research Drive, Durham, North Carolina 27710-2900 USA
- Duke Center For Genomic And Computational Biology, Durham, USA
| |
Collapse
|
|
8
|
Childs PG, Reid S, Salmeron-Sanchez M, Dalby MJ. Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products. Biochem J 2020; 477:3349-3366. [PMID: 32941644 PMCID: PMC7505558 DOI: 10.1042/bcj20190382] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 08/15/2020] [Accepted: 08/24/2020] [Indexed: 12/11/2022]
Abstract
Twenty-five years have passed since the first clinical trial utilising mesenchymal stomal/stem cells (MSCs) in 1995. In this time academic research has grown our understanding of MSC biochemistry and our ability to manipulate these cells in vitro using chemical, biomaterial, and mechanical methods. Research has been emboldened by the promise that MSCs can treat illness and repair damaged tissues through their capacity for immunomodulation and differentiation. Since 1995, 31 therapeutic products containing MSCs and/or progenitors have reached the market with the level of in vitro manipulation varying significantly. In this review, we summarise existing therapeutic products containing MSCs or mesenchymal progenitor cells and examine the challenges faced when developing new therapeutic products. Successful progression to clinical trial, and ultimately market, requires a thorough understanding of these hurdles at the earliest stages of in vitro pre-clinical development. It is beneficial to understand the health economic benefit for a new product and the reimbursement potential within various healthcare systems. Pre-clinical studies should be selected to demonstrate efficacy and safety for the specific clinical indication in humans, to avoid duplication of effort and minimise animal usage. Early consideration should also be given to manufacturing: how cell manipulation methods will integrate into highly controlled workflows and how they will be scaled up to produce clinically relevant quantities of cells. Finally, we summarise the main regulatory pathways for these clinical products, which can help shape early therapeutic design and testing.
Collapse
Affiliation(s)
- Peter G. Childs
- Centre for the Cellular Microenvironment, Division of Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Glasgow, Glasgow G12 8QQ, U.K
- Centre for the Cellular Microenvironment, SUPA Department of Biomedical Engineering, University of Strathclyde, Glasgow G1 1QE, U.K
| | - Stuart Reid
- Centre for the Cellular Microenvironment, SUPA Department of Biomedical Engineering, University of Strathclyde, Glasgow G1 1QE, U.K
| | - Manuel Salmeron-Sanchez
- Centre for the Cellular Microenvironment, Division of Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Glasgow, Glasgow G12 8QQ, U.K
| | - Matthew J. Dalby
- Centre for the Cellular Microenvironment, Institute for Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, U.K
| |
Collapse
|
|
9
|
Kavianpour M, Saleh M, Verdi J. The role of mesenchymal stromal cells in immune modulation of COVID-19: focus on cytokine storm. Stem Cell Res Ther 2020; 11:404. [PMID: 32948252 PMCID: PMC7499002 DOI: 10.1186/s13287-020-01849-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/30/2020] [Accepted: 07/23/2020] [Indexed: 12/11/2022] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) pandemic is quickly spreading all over the world. This virus, which is called SARS-CoV-2, has infected tens of thousands of people. Based on symptoms, the pathogenesis of acute respiratory illness is responsible for highly homogenous coronaviruses as well as other pathogens. Evidence suggests that high inflammation rates, oxidation, and overwhelming immune response probably contribute to pathology of COVID-19. COVID-19 causes cytokine storm, which subsequently leads to acute respiratory distress syndrome (ARDS), often ending up in the death of patients. Mesenchymal stem cells (MSCs) are multipotential stem cells that are recognized via self-renewal capacity, generation of clonal populations, and multilineage differentiation. MSCs are present in nearly all tissues of the body, playing an essential role in repair and generation of tissues. Furthermore, MSCs have broad immunoregulatory properties through the interaction of immune cells in both innate and adaptive immune systems, leading to immunosuppression of many effector activities. MSCs can reduce the cytokine storm produced by coronavirus infection. In a number of studies, the administration of these cells has been beneficial for COVID-19 patients. Also, MSCs may be able to improve pulmonary fibrosis and lung function. In this review, we will review the newest research findings regarding MSC-based immunomodulation in patients with COVID-19.
Collapse
Affiliation(s)
- Maria Kavianpour
- Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahshid Saleh
- Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Javad Verdi
- Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
10
|
Moll G, Drzeniek N, Kamhieh-Milz J, Geissler S, Volk HD, Reinke P. MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy. Front Immunol 2020; 11:1091. [PMID: 32574263 PMCID: PMC7249852 DOI: 10.3389/fimmu.2020.01091] [Citation(s) in RCA: 125] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 05/06/2020] [Indexed: 12/13/2022] Open
Abstract
Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. There is no approved effective therapy for COVID-19, but MSC therapies have shown first promise in the treatment of acute respiratory distress syndrome (ARDS) pneumonia, inflammation, and sepsis, which are among the leading causes of mortality in COVID-19 patients. Many of the critically ill COVID-19 patients are in a hypercoagulable procoagulant state and at high risk for disseminated intravascular coagulation, thromboembolism, and thrombotic multi-organ failure, another cause of high fatality. It is not yet clear whether IV infusion is a safe and effective route of MSC delivery in COVID-19, since MSC-based products express variable levels of highly procoagulant tissue factor (TF/CD142), compromising the cells' hemocompatibility and safety profile. Of concern, IV infusions of poorly characterized MSC products with unchecked (high) TF/CD142 expression could trigger blood clotting in COVID-19 and other vulnerable patient populations and further promote the risk for thromboembolism. In contrast, well-characterized products with robust manufacturing procedures and optimized modes of clinical delivery hold great promise for ameliorating COVID-19 by exerting their beneficial immunomodulatory effects, inducing tissue repair and organ protection. While the need for MSC therapy in COVID-19 is apparent, integrating both innate and adaptive immune compatibility testing into the current guidelines for cell, tissue, and organ transplantation is critical for safe and effective therapies. It is paramount to only use well-characterized, safe MSCs even in the most urgent and experimental treatments. We here propose three steps to mitigate the risk for these vulnerable patients: (1) updated clinical guidelines for cell and tissue transplantation, (2) updated minimal criteria for characterization of cellular therapeutics, and (3) updated cell therapy routines reflecting specific patient needs.
Collapse
Affiliation(s)
- Guido Moll
- BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Norman Drzeniek
- BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universitätsmedizin Berlin, Berlin, Germany
- Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Julian Kamhieh-Milz
- Department of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Sven Geissler
- BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany
- Julius Wolff Institute (JWI), Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Hans-Dieter Volk
- BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany
- Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Petra Reinke
- BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin Center for Advanced Therapies (BECAT), All Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-of Universität zu Berlin, Berlin Institute of Health (BIH), Berlin, Germany
| |
Collapse
|
|
11
|
Shukla V, Seoane-Vazquez E, Fawaz S, Brown L, Rodriguez-Monguio R. The Landscape of Cellular and Gene Therapy Products: Authorization, Discontinuations, and Cost. HUM GENE THER CL DEV 2019; 30:102-113. [PMID: 30968714 DOI: 10.1089/humc.2018.201] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background: Cell and gene therapy products belong to a diverse class of biopharmaceuticals known as advanced therapy medicinal products. Cell and gene therapy products are used for the treatment and prevention of diseases that until recently were only managed chronically. The objective of this study was to examine the characteristics of market authorizations, discontinuations, and prices of cellular and gene therapy products worldwide. Data and Methods: We conducted an electronic search of authorized cell, tissue-engineered, and gene therapy products from the databases of the main drug regulatory agencies. The analysis excluded hematopoietic progenitor cell cord blood products authorized by the U.S. Food and Drug Administration. Price information was derived from the Red Book (Truven Health Analytics) for the United States, health technology assessment agencies for Europe, and other public sector sources and company news for other countries. We also searched the scientific literature for authorizations, discontinuations, and price information using MEDLINE/PubMed, Cochrane Library, Google Scholar, and EMBASE databases. All cost data were converted to U.S. dollars. Descriptive analysis was conducted in this study. Results: There were 52 different cell, tissue engineering and gene therapy products with 69 market authorizations in the world as of December 31, 2018. The products included 18 (34%) cell therapies, 23 (43.4%) tissue engineered products, and 12 (22.6%) gene therapies. There were 21 (30.4% of all authorizations) cell therapy, 26 (37.7%) tissue-engineered, and 22 (31.9%) gene therapy market authorizations. The EMA withdrew the authorization for two tissue engineering products, one cell therapy and one gene therapy, and New Zealand lapsed approval of one cell therapy. Most products were first authorized after 2010, including 10 (83.3%) gene therapies, 13 (72.2%) cell therapies, and 13 (56.5%) tissue-engineered products. The treatment price for four allogenic cell therapies varied from $2,150 in India to $200,000 in Canada. The treatment price for three autologous cell therapies ranged from $61,500 in the United Kingdom to a listed price of $169,206 in the United States. Tissue-engineered treatment prices varied from $400 in South Korea to $123,154 in Japan. Gene therapy treatment prices ranged from $5,501 for tonogenchoncel-L in South Korea to $1,398,321 for alipogene tiparvovec in Germany. Conclusions: A significant number of new cell, tissue, and gene therapies have been approved in the past decade. Most products were conditionally authorized and targeted rare cancers, genetic diseases, and other debilitating diseases. However, there are also products approved for cosmetic reasons. Cell, tissue, and gene therapies are among the most expensive therapies available. Healthcare systems are not prepared to assume the cost of future therapies for a myriad of rare diseases and common diseases of epidemic proportions.
Collapse
Affiliation(s)
- Vaishali Shukla
- Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, California
| | - Enrique Seoane-Vazquez
- Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, California
| | - Souhiela Fawaz
- Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, California
| | - Lawrence Brown
- Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, California
| | - Rosa Rodriguez-Monguio
- Medication Outcomes Center, University of California, San Francisco, San Francisco, California
| |
Collapse
|
|
12
|
Kim K, Grainger DW, Okano T. Utah's cell sheet tissue engineering center. Regen Ther 2019; 11:2-4. [PMID: 31193110 PMCID: PMC6517791 DOI: 10.1016/j.reth.2019.03.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 03/12/2019] [Accepted: 03/19/2019] [Indexed: 11/29/2022] Open
Affiliation(s)
- Kyungsook Kim
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA
| | - David W Grainger
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA
| | - Teruo Okano
- Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.,Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| |
Collapse
|
|
13
|
Kurtz A, Elsallab M, Sanzenbacher R, Abou-El-Enein M. Linking Scattered Stem Cell-Based Data to Advance Therapeutic Development. Trends Mol Med 2019; 25:8-19. [DOI: 10.1016/j.molmed.2018.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 10/20/2018] [Accepted: 10/22/2018] [Indexed: 02/07/2023]
|
|
14
|
Registry Contributions to Strengthen Cell and Gene Therapeutic Evidence. Mol Ther 2018; 26:1172-1176. [PMID: 29685384 DOI: 10.1016/j.ymthe.2018.04.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
|
|
15
|
Gomes-Silva D, Ramos CA. Cancer Immunotherapy Using CAR-T Cells: From the Research Bench to the Assembly Line. Biotechnol J 2018; 13:10.1002/biot.201700097. [PMID: 28960810 PMCID: PMC5966018 DOI: 10.1002/biot.201700097] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 09/20/2017] [Indexed: 11/08/2022]
Abstract
The focus of cancer treatment has recently shifted toward targeted therapies, including immunotherapy, which allow better individualization of care and are hoped to increase the probability of success for patients. Specifically, T cells genetically modified to express chimeric antigen receptors (CARs; CAR-T cells) have generated exciting results. Recent clinical successes with this cutting-edge therapy have helped to push CAR-T cells toward approval for wider use. However, several limitations need to be addressed before the widespread use of CAR-T cells as a standard treatment. Here, a succinct background on adoptive T-cell therapy (ATCT)is given. A brief overview of the structure of CARs, how they are introduced into T cells, and how CAR-T cell expansion and selection is achieved in vitro is then presented. Some of the challenges in CAR design are discussed, as well as the difficulties that arise in large-scale CAR-T cell manufacture that will need to be addressed to achieve successful commercialization of this type of cell therapy. Finally, developments already on the horizon are discussed.
Collapse
Affiliation(s)
- Diogo Gomes-Silva
- Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, 77030, USA
- Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
| | - Carlos A Ramos
- Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, 77030, USA
| |
Collapse
|
|
16
|
Abstract
While advanced therapy medicinal products offer great clinical promise, most EU-approved products have not achieved satisfactory commercial performance. Here we highlight a number of issues that prevent current products from obtaining commercial success and pitfalls that developers must overcome in future product development.
Collapse
|
|
17
|
Tran R, Myers DR, Denning G, Shields JE, Lytle AM, Alrowais H, Qiu Y, Sakurai Y, Li WC, Brand O, Le Doux JM, Spencer HT, Doering CB, Lam WA. Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency. Mol Ther 2017; 25:2372-2382. [PMID: 28780274 PMCID: PMC5628863 DOI: 10.1016/j.ymthe.2017.07.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 07/01/2017] [Accepted: 07/02/2017] [Indexed: 12/24/2022] Open
Abstract
Ex vivo gene therapy using lentiviral vectors (LVs) is a proven approach to treat and potentially cure many hematologic disorders and malignancies but remains stymied by cumbersome, cost-prohibitive, and scale-limited production processes that cannot meet the demands of current clinical protocols for widespread clinical utilization. However, limitations in LV manufacture coupled with inefficient transduction protocols requiring significant excess amounts of vector currently limit widespread implementation. Herein, we describe a microfluidic, mass transport-based approach that overcomes the diffusion limitations of current transduction platforms to enhance LV gene transfer kinetics and efficiency. This novel ex vivo LV transduction platform is flexible in design, easy to use, scalable, and compatible with standard cell transduction reagents and LV preparations. Using hematopoietic cell lines, primary human T cells, primary hematopoietic stem and progenitor cells (HSPCs) of both murine (Sca-1+) and human (CD34+) origin, microfluidic transduction using clinically processed LVs occurs up to 5-fold faster and requires as little as one-twentieth of LV. As an in vivo validation of the microfluidic-based transduction technology, HSPC gene therapy was performed in hemophilia A mice using limiting amounts of LV. Compared to the standard static well-based transduction protocols, only animals transplanted with microfluidic-transduced cells displayed clotting levels restored to normal.
Collapse
Affiliation(s)
- Reginald Tran
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | - David R Myers
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | | | - Jordan E Shields
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Allison M Lytle
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Graduate Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, GA 30322, USA
| | - Hommood Alrowais
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Yongzhi Qiu
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | - Yumiko Sakurai
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | - William C Li
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | - Oliver Brand
- School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
| | - Joseph M Le Doux
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | - H Trent Spencer
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Graduate Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, GA 30322, USA
| | - Christopher B Doering
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Graduate Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, GA 30322, USA.
| | - Wilbur A Lam
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
| |
Collapse
|
|
18
|
The path to successful commercialization of cell and gene therapies: empowering patient advocates. Cytotherapy 2016; 19:293-298. [PMID: 27956199 DOI: 10.1016/j.jcyt.2016.10.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 10/28/2016] [Accepted: 10/31/2016] [Indexed: 12/31/2022]
Abstract
Often, novel gene and cell therapies provide hope for many people living with incurable diseases. To facilitate and accelerate a successful regulatory approval and commercialization path for effective, safe and affordable cell and gene therapies, the involvement of patient advocacy groups (PAGs) should be considered early in the development process. This report provides a thorough overview of the various roles PAGs play in the clinical translation of cell and gene therapies and how they can bring about positive changes in the regulatory process, infrastructure improvements and market stability.
Collapse
|
|
19
|
Abou-El-Enein M, Duda GN, Gruskin EA, Grainger DW. Strategies for Derisking Translational Processes for Biomedical Technologies. Trends Biotechnol 2016; 35:100-108. [PMID: 27499276 DOI: 10.1016/j.tibtech.2016.07.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 07/18/2016] [Accepted: 07/19/2016] [Indexed: 12/18/2022]
Abstract
Inefficient translational processes for technology-oriented biomedical research have led to some prominent and frequent failures in the development of many leading drug candidates, several designated investigational drugs, and some medical devices, as well as documented patient harm and postmarket product withdrawals. Derisking this process, particularly in the early stages, should increase translational efficiency and streamline resource utilization, especially in an academic setting. In this opinion article, we identify a 12-step guideline for reducing risks typically associated with translating medical technologies as they move toward prototypes, preclinical proof of concept, and possible clinical testing. Integrating the described 12-step process should prove valuable for improving how early-stage academic biomedical concepts are cultivated, culled, and manicured toward intended clinical applications.
Collapse
Affiliation(s)
- Mohamed Abou-El-Enein
- Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
| | - Georg N Duda
- Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; Julius Wolff Institute (JWI), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
| | | | - David W Grainger
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA
| |
Collapse
|
|
20
|
Abou-El-Enein M, Bauer G, Medcalf N, Volk HD, Reinke P. Putting a price tag on novel autologous cellular therapies. Cytotherapy 2016; 18:1056-1061. [PMID: 27288308 DOI: 10.1016/j.jcyt.2016.05.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 05/05/2016] [Accepted: 05/09/2016] [Indexed: 12/24/2022]
Abstract
Cell therapies, especially autologous therapies, pose significant challenges to researchers who wish to move from small, probably academic, methods of manufacture to full commercial scale. There is a dearth of reliable information about the costs of operation, and this makes it difficult to predict with confidence the investment needed to translate the innovations to the clinic, other than as small-scale, clinician-led prescriptions. Here, we provide an example of the results of a cost model that takes into account the fixed and variable costs of manufacture of one such therapy. We also highlight the different factors that influence the product final pricing strategy. Our findings illustrate the need for cooperative and collective action by the research community in pre-competitive research to generate the operational models that are much needed to increase confidence in process development for these advanced products.
Collapse
Affiliation(s)
- Mohamed Abou-El-Enein
- Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow, Berlin, Germany; Department of Nephrology and Internal Intensive Care, Charité-University Medicine, Campus Virchow, Berlin, Germany.
| | - Gerhard Bauer
- Institute for Regenerative Cures, University of California Davis, Sacramento, CA, USA
| | - Nicholas Medcalf
- Wolfson School of Mechanical, Electrical and Manufacturing Engineering, Loughborough University, Loughborough, UK
| | - Hans-Dieter Volk
- Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow, Berlin, Germany; Institute of Medical Immunology, Charité University Medicine, Campus Virchow, Berlin, Germany
| | - Petra Reinke
- Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow, Berlin, Germany; Department of Nephrology and Internal Intensive Care, Charité-University Medicine, Campus Virchow, Berlin, Germany
| |
Collapse
|
|
21
|
Abou-El-Enein M, Bauer G, Reinke P. Gene therapy: a possible future standard for HIV care. Trends Biotechnol 2016; 33:374-6. [PMID: 26088914 DOI: 10.1016/j.tibtech.2015.03.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 03/09/2015] [Accepted: 03/20/2015] [Indexed: 11/28/2022]
Abstract
Despite undeniable accomplishments in developing cell and gene therapeutic strategies to combat HIV infection, key social, economic, and policy-related challenges still need to be overcome for any future commercialization efforts of these novel therapies to be successful. Here, we address these challenges and structure a framework for eradicating HIV/AIDS using gene therapy.
Collapse
Affiliation(s)
- Mohamed Abou-El-Enein
- Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Campus Virchow, Berlin, Germany; Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
| | - Gerhard Bauer
- University of California Davis, Institute For Regenerative Cures (IRC) Sacramento, CA, USA
| | - Petra Reinke
- Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Medicine Berlin, Campus Virchow, Berlin, Germany; Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany
| |
Collapse
|
|
22
|
|
|
23
|
Foldvari M, Chen DW, Nafissi N, Calderon D, Narsineni L, Rafiee A. Non-viral gene therapy: Gains and challenges of non-invasive administration methods. J Control Release 2015; 240:165-190. [PMID: 26686079 DOI: 10.1016/j.jconrel.2015.12.012] [Citation(s) in RCA: 172] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 11/26/2015] [Accepted: 12/09/2015] [Indexed: 12/20/2022]
Abstract
Gene therapy is becoming an influential part of the rapidly increasing armamentarium of biopharmaceuticals for improving health and combating diseases. Currently, three gene therapy treatments are approved by regulatory agencies. While these treatments utilize viral vectors, non-viral alternative technologies are also being developed to improve the safety profile and manufacturability of gene carrier formulations. We present an overview of gene-based therapies focusing on non-viral gene delivery systems and the genetic therapeutic tools that will further revolutionize medical treatment with primary focus on the range and development of non-invasive delivery systems for dermal, transdermal, ocular and pulmonary administrations and perspectives on other administration methods such as intranasal, oral, buccal, vaginal, rectal and otic delivery.
Collapse
Affiliation(s)
- Marianna Foldvari
- School of Pharmacy, Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Center for Bioengineering and Biotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
| | - Ding Wen Chen
- School of Pharmacy, Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Center for Bioengineering and Biotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada
| | - Nafiseh Nafissi
- School of Pharmacy, Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Center for Bioengineering and Biotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada
| | - Daniella Calderon
- School of Pharmacy, Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Center for Bioengineering and Biotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada
| | - Lokesh Narsineni
- School of Pharmacy, Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Center for Bioengineering and Biotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada
| | - Amirreza Rafiee
- School of Pharmacy, Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Center for Bioengineering and Biotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada
| |
Collapse
|
|
24
|
Ducret M, Fabre H, Degoul O, Atzeni G, McGuckin C, Forraz N, Alliot-Licht B, Mallein-Gerin F, Perrier-Groult E, Farges JC. Manufacturing of dental pulp cell-based products from human third molars: current strategies and future investigations. Front Physiol 2015; 6:213. [PMID: 26300779 PMCID: PMC4526817 DOI: 10.3389/fphys.2015.00213] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 07/16/2015] [Indexed: 01/01/2023] Open
Abstract
In recent years, mesenchymal cell-based products have been developed to improve surgical therapies aimed at repairing human tissues. In this context, the tooth has recently emerged as a valuable source of stem/progenitor cells for regenerating orofacial tissues, with easy access to pulp tissue and high differentiation potential of dental pulp mesenchymal cells. International guidelines now recommend the use of standardized procedures for cell isolation, storage and expansion in culture to ensure optimal reproducibility, efficacy and safety when cells are used for clinical application. However, most dental pulp cell-based medicinal products manufacturing procedures may not be fully satisfactory since they could alter the cells biological properties and the quality of derived products. Cell isolation, enrichment and cryopreservation procedures combined to long-term expansion in culture media containing xeno- and allogeneic components are known to affect cell phenotype, viability, proliferation and differentiation capacities. This article focuses on current manufacturing strategies of dental pulp cell-based medicinal products and proposes a new protocol to improve efficiency, reproducibility and safety of these strategies.
Collapse
Affiliation(s)
- Maxime Ducret
- Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, UMR5305 Centre National de la Recherche Scientifique/Université Claude Bernard Lyon 1 Lyon, France ; Faculté d'Odontologie, Université de Lyon, Université Claude Bernard Lyon 1 Lyon, France ; Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires Lyon, France
| | - Hugo Fabre
- Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, UMR5305 Centre National de la Recherche Scientifique/Université Claude Bernard Lyon 1 Lyon, France
| | - Olivier Degoul
- CTI-BIOTECH, Cell Therapy Research Institute Meyzieu, France
| | | | - Colin McGuckin
- CTI-BIOTECH, Cell Therapy Research Institute Meyzieu, France
| | - Nico Forraz
- CTI-BIOTECH, Cell Therapy Research Institute Meyzieu, France
| | - Brigitte Alliot-Licht
- Faculté d'Odontologie, Institut National de la Santé et de la Recherche Médicale UMR1064, Centre de Recherche en Transplantation et Immunologie, Université de Nantes Nantes, France
| | - Frédéric Mallein-Gerin
- Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, UMR5305 Centre National de la Recherche Scientifique/Université Claude Bernard Lyon 1 Lyon, France
| | - Emeline Perrier-Groult
- Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, UMR5305 Centre National de la Recherche Scientifique/Université Claude Bernard Lyon 1 Lyon, France
| | - Jean-Christophe Farges
- Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique, UMR5305 Centre National de la Recherche Scientifique/Université Claude Bernard Lyon 1 Lyon, France ; Faculté d'Odontologie, Université de Lyon, Université Claude Bernard Lyon 1 Lyon, France ; Hospices Civils de Lyon, Service de Consultations et Traitements Dentaires Lyon, France
| |
Collapse
|