Intravenous infusion of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells as a potential treatment for patients with COVID-19 pneumonia

Zhang, Yingxin; Ding, Jie; Ren, Shaoda; Wang, Weihua; Yang, Yong; Li, Shuangjing; Meng, Min; Wu, Tiejun; Liu, Daliang; Tian, Shuo; Tian, Hui; Chen, Shuangfeng; Zhou, Changhui

doi:10.1186/s13287-020-01725-4

Cited by 119 publications

(118 citation statements)

References 18 publications

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“…Encouragingly, Leng and colleagues reported that in the UC-MSCs treated group, the clinical parameters, including the oxygen saturation, inflammation and tissue injury biomarkers, and aspartic aminotransferase, were improved or normalized [220]. Moreover, a positive clinical outcome was also demonstrated in a severe COVID-19 patient treated with intravenous infusion of human umbilical cord Wharton's Jelly-derived MSCs [222]. These limited clinical data imply that MSCs exert their anti-inflammatory and immunomodulatory actions in COVID-19 patients.…”

Section: Anti-obesity-related Therapies: Potential Strategy For Combamentioning

confidence: 99%

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Ritter

Kreis

Louwen

et al. 2020

IJMS

109

111

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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: Anti-obesity-related Therapies: Potential Strategy For Combamentioning

confidence: 99%

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Ritter

Kreis

Louwen

et al. 2020

IJMS

109

111

View full text Add to dashboard Cite

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“…WJ-MSCs are becoming an interesting tool for allogenic transplantation in different kinds of disease, and also for COVID-19 complications [6][7][8]. Therefore, understanding the behavior of MSCs within the recipient tissues could be of great interest in assessing the safety of this kind of procedure.…”

Section: Discussionmentioning

confidence: 99%

“…The use of WJ-MSCs is emerging in allogenic transplantation for different kinds of patients, due to their immunomodulatory properties [4,5]. Interestingly, in recent months, intravenous infusion of allogenic WJ-MSCs has been successfully used for the treatment of patients with COVID-19 pneumonia [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Behavioral Changes in Stem-Cell Potency by HepG2-Exhausted Medium

Balzano

Garroni

Cruciani

et al. 2020

Cells

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Wharton jelly mesenchymal stem cells (WJ-MSCs) are able to differentiate into different cell lineages upon stimulation. This ability is closely related to the perfect balance between the pluripotency-related genes, which control stem-cell proliferation, and genes able to orchestrate the appearance of a specific phenotype. Here we studied the expression of stemness-related genes, epigenetic regulators (DNMT1, SIRT1), miRNAs (miR-145, miR-148, and miR-185) related to stemness, exosomes, the cell-cycle regulators p21 (WAF1/CIP1) and p53, and the senescence-associated genes (p16, p19, and hTERT). Cells were cultured in the presence or absence of the human hepatocarcinoma cell line HepG2-exhausted medium, to evaluate changes in stemness, differentiation capability, and senescence sensibility. Our results showed the overexpression of SIRT1 and reduced levels of p21 mRNA. Moreover, we observed a downregulation of DNMT1, and a simultaneous overexpression of Oct-4 and c-Myc. These findings suggest that WJ-MSCs are more likely to retain a stem phenotype and sometimes to switch to a highly undifferentiable proliferative-like behavior if treated with medium exhausted by human HepG2 cell lines.

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“…COVID-19 is characterized by an acute respiratory illness caused by a new coronavirus type named as "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). The COVID-19 is clinically heterogeneous, patients may be asymptomatic or have light, moderated, severe or critical symptoms [101][102][103][104].…”

Section: Msc Therapy In Viral Infections: Preclinical and Clinical Apmentioning

confidence: 99%

“…Therefore, therapy based on the use of hWJCs may be effective in the treatment of patients with COVID-19 [104].…”

Section: Msc Therapy In Viral Infections: Preclinical and Clinical Apmentioning

confidence: 99%

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

Rocha

Oliveira

Noronha

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied.

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Intravenous infusion of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells as a potential treatment for patients with COVID-19 pneumonia

Cited by 119 publications

References 18 publications

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

Behavioral Changes in Stem-Cell Potency by HepG2-Exhausted Medium

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

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