Mesenchymal Stem Cell Therapy of Pulmonary Fibrosis

Chuang, Hong-Meng; Shih, Tina Emily; Lu, Kang; Tsai, Shang-Chun; Harn, Horng‐Jyh; Ho, Li‐Ing

doi:10.1177/0963689718787501

Cited by 42 publications

(37 citation statements)

References 64 publications

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“…Interestingly, ASCs/MSCs have been reported as cellular therapy option for pulmonary fibrosis and bronchopulmonary dysplasia by regulating immune cells inside the lung tissue, modulating trans-differentiation of different cell types including fibroblasts, and secreting various growth factors [96,97]. Furthermore, these cells could be used in infectious diseases because of their immunosuppressive or immune enhancement effects depending on their cytokine production and on the context of the immune response [98].…”

Section: Ascs Mscs Obesity and Covid-19mentioning

confidence: 99%

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Ritter

Kreis

Louwen

et al. 2020

IJMS

116

122

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The coronavirus disease 2019 COVID-19 pandemic is rapidly spreading worldwide and is becoming a major public health crisis. Increasing evidence demonstrates a strong correlation between obesity and the COVID-19 disease. We have summarized recent studies and addressed the impact of obesity on COVID-19 in terms of hospitalization, severity, mortality, and patient outcome. We discuss the potential molecular mechanisms whereby obesity contributes to the pathogenesis of COVID-19. In addition to obesity-related deregulated immune response, chronic inflammation, endothelium imbalance, metabolic dysfunction, and its associated comorbidities, dysfunctional mesenchymal stem cells/adipose-derived mesenchymal stem cells may also play crucial roles in fueling systemic inflammation contributing to the cytokine storm and promoting pulmonary fibrosis causing lung functional failure, characteristic of severe COVID-19. Moreover, obesity may also compromise motile cilia on airway epithelial cells and impair functioning of the mucociliary escalators, reducing the clearance of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Obese diseased adipose tissues overexpress the receptors and proteases for the SARS-CoV-2 entry, implicating its possible roles as virus reservoir and accelerator reinforcing violent systemic inflammation and immune response. Finally, anti-inflammatory cytokines like anti-interleukin 6 and administration of mesenchymal stromal/stem cells may serve as potential immune modulatory therapies for supportively combating COVID-19. Obesity is conversely related to the development of COVID-19 through numerous molecular mechanisms and individuals with obesity belong to the COVID-19-susceptible population requiring more protective measures.

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Section: Ascs Mscs Obesity and Covid-19mentioning

confidence: 99%

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Ritter

Kreis

Louwen

et al. 2020

IJMS

116

122

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“…9 MSCs are considered to suppress the over-activated inflammatory response, promote recovery of lung function, and potentially influence the progress of pulmonary fibrosis. 10 Thus, the use of MSCs to improve the clinical outcome of the patients with severe cases of COVID-19 disease requires evaluation.…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial

Meng

Wang

et al. 2020

Sig Transduct Target Ther

267

244

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No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non-randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease. The study enrolled 18 hospitalized patients with COVID-19 (n = 9 for each group). The treatment group received three cycles of intravenous infusion of UC-MSCs (3 × 10 7 cells per infusion) on days 0, 3, and 6. Both groups received standard COVID-treatment regimens. Adverse events, duration of clinical symptoms, laboratory parameters, length of hospitalization, serial chest computed tomography (CT) images, the PaO 2 /FiO 2 ratio, dynamics of cytokines, and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed. No serious UC-MSCs infusion-associated adverse events were observed. Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion. Mechanical ventilation was required in one patient in the treatment group compared with four in the control group. All patients recovered and were discharged. Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated. Phase 2/3 randomized, controlled, double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.

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“…Clinical and animal studies suggest it is as effective as pharmaceutical therapies in treating PF. 129 Although they have uncertain mechanisms of action, MSCs have been proven to exert a modulating effect in lung inflammation and fibrosis. 130 Experimental models on human tissue and animal studies have also reported that MSCs achieve excellent outcomes in ALI/ARDS by attenuating the severity of lung injury and by reducing mortality.…”

Section: Discussionmentioning

confidence: 99%

“A Chain Only as Strong as Its Weakest Link”: An Up-to-Date Literature Review on the Bidirectional Interaction of Pulmonary Fibrosis and COVID-19

Criṣan-Dabija

Pavel²,

Popa³

et al. 2020

J. Proteome Res.

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The COVID-19 pandemic rapidly became a worldwide healthcare emergency affecting millions of people, with poor outcomes for patients with chronic conditions and enormous pressure on healthcare systems. Pulmonary fibrosis (PF) has been cited as a risk factor for a more severe evolution of COVID-19, primarily because its acute exacerbations are already associated with high mortality. We reviewed the available literature on biochemical, pathophysiological, and pharmacological mechanisms of PF and COVID-19 in an attempt to foresee the particular risk of infection and possible evolution of PF patients if infected with SARS-COV-2. We also analyzed the possible role of medication and risk factors (such as smoking) in the disease’s evolution and clinical course. We found out that there is a complexity of interactions between coexisting idiopathic pulmonary fibrosis/interstitial lung disease (ILD) and COVID-19 disease. Also, patients recovering from severe COVID-19 disease are at serious risk of developing PF. Smokers seem to have, in theory, a chance for a better outcome if they develop a severe form of COVID-19 but statistically are at much higher risk of dying if they become critically ill.

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Mesenchymal Stem Cell Therapy of Pulmonary Fibrosis

Cited by 42 publications

References 64 publications

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial

“A Chain Only as Strong as Its Weakest Link”: An Up-to-Date Literature Review on the Bidirectional Interaction of Pulmonary Fibrosis and COVID-19

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