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      Regenerative and translational medicine in COPD: hype and hope

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          Abstract

          COPD is a common, preventable and usually progressive disease associated with an enhanced chronic inflammatory response in the airways and lung, generally caused by exposure to noxious particles and gases. It is a treatable disease characterised by persistent respiratory symptoms and airflow limitation due to abnormalities in the airways and/or alveoli. COPD is currently the third leading cause of death worldwide, representing a serious public health problem and a high social and economic burden. Despite significant advances, effective clinical treatments have not yet been achieved. In this scenario, cell-based therapies have emerged as potentially promising therapeutic approaches. However, there are only a few published studies of cell-based therapies in human patients with COPD and a small number of ongoing clinical trials registered on clinicaltrials.gov. Despite the advances and interesting results, numerous doubts and questions remain about efficacy, mechanisms of action, culture conditions, doses, timing, route of administration and conditions related to homing and engraftment of the infused cells. This article presents the state of the art of cell-based therapy in COPD. Clinical trials that have already been completed and with published results are discussed in detail. We also discuss the questions that remain unanswered about cell-based regenerative and translational medicine for COPD.

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          This review describes the current state of the art of cell-based, regenerative and translational medicine in COPD, presenting the clinical trials already completed and with published results. https://bit.ly/3P08Bmq

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          Most cited references139

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          Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma. In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017. Methods Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex. Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases. We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs. Findings In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9–584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990. Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia. The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically. Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8–7·2] of all deaths), behind cardiovascular diseases and neoplasms. Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578–4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%. However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%). In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD. In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes. Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world. Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions. Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men. Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region. Interpretation Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990. Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis. Funding Bill & Melinda Gates Foundation.
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            Mesenchymal stem cell perspective: cell biology to clinical progress

            The terms MSC and MSCs have become the preferred acronym to describe a cell and a cell population of multipotential stem/progenitor cells commonly referred to as mesenchymal stem cells, multipotential stromal cells, mesenchymal stromal cells, and mesenchymal progenitor cells. The MSCs can differentiate to important lineages under defined conditions in vitro and in limited situations after implantation in vivo. MSCs were isolated and described about 30 years ago and now there are over 55,000 publications on MSCs readily available. Here, we have focused on human MSCs whenever possible. The MSCs have broad anti-inflammatory and immune-modulatory properties. At present, these provide the greatest focus of human MSCs in clinical testing; however, the properties of cultured MSCs in vitro suggest they can have broader applications. The medical utility of MSCs continues to be investigated in over 950 clinical trials. There has been much progress in understanding MSCs over the years, and there is a strong foundation for future scientific research and clinical applications, but also some important questions remain to be answered. Developing further methods to understand and unlock MSC potential through intracellular and intercellular signaling, biomedical engineering, delivery methods and patient selection should all provide substantial advancements in the coming years and greater clinical opportunities. The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.
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              Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities

              Mesenchymal stromal cells (MSCs) have been the subject of clinical trials for more than a generation, and the outcomes of advanced clinical trials have fallen short of expectations raised by encouraging pre-clinical animal data in a wide array of disease models. In this Perspective, important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analyses of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                30 September 2023
                26 July 2023
                : 32
                : 169
                : 220223
                Affiliations
                [1 ]Department of Genetics, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, Brazil
                [2 ]Laboratory of Genetics and Cell Therapy – GenTe Cel, Department of Biotechnology, São Paulo State University (UNESP), Assis, Brazil
                [3 ]Biomedical Sciences Institute, Butantan Institute, Technological Research Institute, University of São Paulo (USP), São Paulo, Brazil
                [4 ]Laboratory of Preclinical Research of Natural Products, Paranaense University (UNIPAR), Umuarama, Brazil
                [5 ]Health and Biotechnology Institute, Federal University of Amazonas (UFAM), Coari, Brazil
                [6 ]Faculty of Health Sciences, University of Western São Paulo (UNOESTE), São Paulo, Brazil
                [7 ]São Lucas Research and Education Institute (IEP - São Lucas), TechLife, São Paulo, Brazil
                Author notes
                Corresponding author: João Tadeu Ribeiro-Paes ( ribeiro.paes@ 123456unesp.br )
                Author information
                https://orcid.org/0000-0002-0733-1975
                https://orcid.org/0000-0001-8086-1262
                Article
                ERR-0223-2022
                10.1183/16000617.0223-2022
                10369169
                116865d4-6d91-4952-b0a8-72a8403b923b
                Copyright ©The authors 2023

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

                History
                : 14 November 2022
                : 23 May 2023
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