Transplantation of adipose-derived mesenchymal stem cells attenuates pulmonary fibrosis of silicosis via anti-inflammatory and anti-apoptosis effects in rats

Liang

et al. 2020

Preprint

Background: The coronavirus disease 2019 (COVID-19) causing a cluster of respiratory infections in Wuhan, China, is identified in December 2019. The main symptoms are defined as fever, cough, shortness of breath, with early symptom of sputum, acute respiratory distress syndrome (ARDS), and the final lung injury and pulmonary fibrosis. Currently, there is no effective method to cure it. Mesenchymal stem cell (MSC) therapy is an immediate need for treating COVID-19 especially severe patients at present.Methods: We describe the two confirmed case of COVID-19 severe patients in Hangzhou, China to explore the role of menstrual blood-derived MSC in the treatment of SARS-CoV-2 infection. Furthermore, we mimic disease model of pulmonary fibrosis in mice to assess the role of MSC. Then, a co-culture system to investigate the underlying mechanism between MSC and pulmonary-associated cells by a series of Physiological, biochemical, bioinformatics analysis.Results: MSC transplantation increases the immune indicators (including lymphocytes) and decreases inflammatory indicators (such as IL-6, IL-10, TNF, and IFN). More importantly, the two patients alleviated symptom and discharged after 3 weeks’ treatment with MSC. Additionally, MSCs exhibit an anti-inflammatory role through suppressing some inflammatory factors (RANTES, GM-CSF, MIG-1g, MCP-5, Eotaxin), which is anastomotic to current clinical study using MSC to treat COVID-19. Conclusions: This is the first report using menstrual blood-derived MSC in treating COVID-19 patients. From our clinical results, we hold one idea that MSCs reduced inflammatory effect to defend cytokine storm. The underlying mechanism is probably that MSCs inhibit epithelia cell apoptosis and reduce the secretion of inflammatory factors to prevent myofibroblasts activity. MSC provides an alternative method for treating COVID-19 particularly some patients with ARDS or subsequent pulmonary fibrosis.Trial registration: This clinical trial was submitted to and approved by the Ethics Committee of the First Affiliated Hospital, Collage of Medicine, Zhejiang University. MSC administration in patient with COVID-19 was conducted in a single center and open-label clinical trial (ChiCTR2000029606).

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Menstrual blood-derived mesenchymal stem cells provide new insights into the treatment of coronavirus disease 2019 (COVID-19)

Liang

et al. 2020

Preprint

Pediatrics International

“…In this CAWS‐based mouse model, similar histological features of vasculitis in the aortic root and coronary arteritis in KD have been reported . ADSCs inhibited the production of pro‐inflammatory cytokines such as TNF‐α, IL‐12, and IL‐1β in activated macrophages . This suggests that ADSCs may play a role in preventing vasculitis and prolonging survival via suppression of pro‐inflammatory cytokines.…”

Section: Discussionsupporting

confidence: 71%

“…This suggests that ADSCs may play a role in preventing vasculitis and prolonging survival via suppression of pro‐inflammatory cytokines. Previous data have highlighted that the therapeutic potential of ADSCs stems from the regulation of inflammatory process that develop during disease . The effects of ADSCs on coronary arteritis during KD, however, have been understudied.…”

Section: Discussionmentioning

confidence: 99%

Adipose tissue‐derived stem cells suppress coronary arteritis of Kawasaki disease in vivo

Uchimura

Ueda

Fukazawa

et al. 2020

Background: Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo. Methods: Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. Results: The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1b, IL-12, IL-17, RANTES, INF-c, and TNF-a, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. Conclusions: These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD.

Stem Cells Translational Medicine

“…With reference to enhanced expression of genes implicated in fibrotic responses in animals infused with ASCs, it should be noted that the current model is acute and fibrosis cannot be detected at histological level. In more chronic settings, infusion of MSCs have been shown to exert antifibrotic effects in the lungs in several experimental settings, including lung fibrosis induced by bleomycin , white smoke , silica , and chronic allergic airway inflammation . These preclinical data led several investigators to suggest infusion of MSCs as a potential novel therapeutic for lung fibrosis in patients .…”

Section: Discussionmentioning

confidence: 99%

Human Adipose-Derived Mesenchymal Stem Cells Modify Lung Immunity and Improve Antibacterial Defense in Pneumosepsis Caused by Klebsiella pneumoniae

Perlee

Vos

Scicluna

et al. 2019

Adult mesenchymal stem cells exert immunomodulatory effects that might improve the host response during sepsis. Knowledge on the effect of adipose‐derived mesenchymal stem cells (ASCs) in sepsis is limited. Klebsiella (K.) pneumoniae is a common cause of gram‐negative pneumonia and sepsis. This study sought to determine the effect of human ASCs on the host response during pneumosepsis in mice. Mice were infected with K. pneumoniae via the airways to induce a gradually evolving infection in the lung culminating pneumosepsis. One or 6 hours after infection, mice were infused intravenously with ASCs or vehicle, and euthanized after 16 hours or 48 hours, respectively. The effects of freshly cultured and cryopreserved ASCs were compared, the latter formulation being more clinically relevant. Intravenously administered ASCs were visualized in lung tissue by immunostaining at 1 and 3 hours, but not at 15 hours after infusion. Although early after infection, ASCs did not or only modestly influence bacterial loads, they reduced bacterial burdens in lungs and distant organs at 48 hours. ASCs reduced the lung levels of pro‐inflammatory cytokines and attenuated lung pathology, but did not influence distant organ injury. ASCs strongly modified the lung transcriptome in uninfected mice and especially mice with pneumosepsis. Cryopreserved and cultured ASCs induced largely similar effects on the lung transcriptome. These data indicate that human ASCs induce profound immune modulatory effects in the lungs, resulting in reduced bacterial burdens and lung inflammation during pneumosepsis caused by a common human pathogen, suggesting that ASCs may be an adjunctive therapeutic in this condition. Stem Cells Translational Medicine 2019;8:785&796