Present and Future of Bronchopulmonary Dysplasia

Bonadies, Luca; Zaramella, Patrizia; Porzionato, Andrea; Perilongo, Giorgio; Muraca, Maurizio; Baraldi, Eugenio

doi:10.3390/jcm9051539

Cited by 92 publications

(80 citation statements)

References 233 publications

(255 reference statements)

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“…While the initial study aimed to address only safety issues, the authors now based the dose-escalation on data derived from studies in humans and animals that proved therapeutic efficacy [ 80 , 81 , 82 ]. For a comprehensive list of further ongoing phase I and II MSC trials, we refer to this recently published reference [ 83 ].…”

Section: Do the Results From Msc Application Within First Phase I mentioning

confidence: 99%

MSC Based Therapies to Prevent or Treat BPD—A Narrative Review on Advances and Ongoing Challenges

Goetz

Kremer

Behnke

et al. 2021

IJMS

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Bronchopulmonary dysplasia (BPD) remains one of the most devastating consequences of preterm birth resulting in life-long restrictions in lung function. Distorted lung development is caused by its inflammatory response which is mainly provoked by mechanical ventilation, oxygen toxicity and bacterial infections. Dysfunction of resident lung mesenchymal stem cells (MSC) represents one key hallmark that drives BPD pathology. Despite all progress in the understanding of pathomechanisms, therapeutics to prevent or treat BPD are to date restricted to a few drugs. The limited therapeutic efficacy of established drugs can be explained by the fact that they fail to concurrently tackle the broad spectrum of disease driving mechanisms and by the huge overlap between distorted signal pathways of lung development and inflammation. The great enthusiasm about MSC based therapies as novel therapeutic for BPD arises from the capacity to inhibit inflammation while simultaneously promoting lung development and repair. Preclinical studies, mainly performed in rodents, raise hopes that there will be finally a broadly acting, efficient therapy at hand to prevent or treat BPD. Our narrative review gives a comprehensive overview on preclinical achievements, results from first early phase clinical studies and challenges to a successful translation into the clinical setting.

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Section: Do the Results From Msc Application Within First Phase I mentioning

confidence: 99%

MSC Based Therapies to Prevent or Treat BPD—A Narrative Review on Advances and Ongoing Challenges

Goetz

Kremer

Behnke

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In addition, Tan et al ( 130 ) reported that the release of EVs from hAECs administered intranasally exerted similar beneficial effects to MSCs with significant reduction in lung inflammation, improvement in tissue-to-airspace ratio and reduction in fibrosis in bleomycin-challenged aged mice ( 130 ). Willis et al ( 129 ) and Bonadies et al ( 131 ) suggested that MSCs and EVs are two most revolutionary treatments for BPD, not only effective in the prevention of BPD but also may potentially reverse the complications in children diagnosed with BPD ( 129 , 131 ).…”

Section: Mechanisms Of Function Of Placenta and Umbilical Cord-derivementioning

confidence: 99%

A Review of Placenta and Umbilical Cord-Derived Stem Cells and the Immunomodulatory Basis of Their Therapeutic Potential in Bronchopulmonary Dysplasia

et al. 2021

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Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.

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“…A recently published analysis in 28 BPD-PH patients demonstrated that PH mostly resolved at 2.5 years in patients surviving beyond a corrected age of 6 months. On the other hand, there are reports on PA pressure elevation in former BPD patients, diagnosed at school age or in adolescence [ 184 , 185 , 186 ]. Currently, larger prospective outcome studies to assess the further course of this disease are lacking.…”

Section: Group 3 Ph ( Table 1 )mentioning

confidence: 99%

Focused Update on Pulmonary Hypertension in Children—Selected Topics of Interest for the Adult Cardiologist

2020

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Pulmonary hypertensive vascular disease (PHVD), and pulmonary hypertension (PH), which is a broader term, are severe conditions associated with high morbidity and mortality at all ages. Treatment guidelines in childhood are widely adopted from adult data and experience, though big differences may exist regarding aetiology, concomitant conditions and presentation. Over the past few years, paediatric aspects have been incorporated into the common guidelines, which currently address both children and adults with pulmonary hypertension (PH). There are multiple facets of PH in the context of cardiac conditions in childhood. Apart from Eisenmenger syndrome (ES), the broad spectrum of congenital heart disease (CHD) comprises PH in failing Fontan physiology, as well as segmental PH. In this review we provide current data and novel aspects on the pathophysiological background and individual management concepts of these conditions. Moreover, we focus on paediatric left heart failure with PH and its challenging issues, including end stage treatment options, such as mechanical support and paediatric transplantation. PH in the context of rare congenital disorders, such as Scimitar Syndrome and sickle cell disease is discussed. Based on current data, we provide an overview on multiple underlying mechanisms of PH involved in these conditions, and different management strategies in children and adulthood. In addition, we summarize the paediatric aspects and the pros and cons of the recently updated definitions of PH. This review provides deeper insights into some challenging conditions of paediatric PH in order to improve current knowledge and care for children and young adults.

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Present and Future of Bronchopulmonary Dysplasia

Cited by 92 publications

References 233 publications

MSC Based Therapies to Prevent or Treat BPD—A Narrative Review on Advances and Ongoing Challenges

MSC Based Therapies to Prevent or Treat BPD—A Narrative Review on Advances and Ongoing Challenges

A Review of Placenta and Umbilical Cord-Derived Stem Cells and the Immunomodulatory Basis of Their Therapeutic Potential in Bronchopulmonary Dysplasia

Focused Update on Pulmonary Hypertension in Children—Selected Topics of Interest for the Adult Cardiologist

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