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      Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

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          Abstract

          BACKGROUND

          Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells (ADSCs) are an effective therapeutic approach for managing coronavirus disease 2019 (COVID-19); however, further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors (TFs) and cytokine release in peripheral blood mononuclear cells (PBMCs).

          AIM

          To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer (CRC) patients with severe COVID-19 (CRC + patients).

          METHODS

          PBMCs from CRC + patients (PBMCs-C + ) and age-matched CRC patients (PBMCs-C) were stimulated and cultured in the presence/absence of ADSCs. The mRNA levels of T-box TF TBX21 (T-bet), GATA binding protein 3 (GATA-3), RAR-related orphan receptor C (RORC), and forkhead box P3 (FoxP3) in the PBMCs were determined by reverse transcriptase-polymerase chain reaction. Culture supernatants were evaluated for levels of interferon gamma (IFN-γ), interleukin 4 (IL-4), IL-17A, and transforming growth factor beta 1 (TGF-β1) using an enzyme-linked immunosorbent assay.

          RESULTS

          Compared with PBMCs-C, PBMCs-C + exhibited higher mRNA levels of T-bet and RORC, and increased levels of IFN-γ and IL-17A. Additionally, a significant decrease in FoxP3 mRNA and TGF-β1, as well as an increase in T-bet/GATA-3, RORC/FoxP3, IFN-γ/IL-4, and IL-17A/TGF-β1 ratios were observed in PBMCs-C + . Furthermore, ADSCs significantly induced a functional regulatory T cell (Treg) subset, as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels. This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC, release of IFN-γ and IL-17A, and T-bet/GATA-3, RORC/FoxP3, IFN-γ/IL-4, and IL-17A/TGF-β1 ratios, compared with the PBMCs-C + alone.

          CONCLUSION

          The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C + , favoring Treg responses. Thus, ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.

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          Transplantation of ACE2 - Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

          Zikuan Leng, Rongjia Zhu, Wei Wei Hou … (2020)
          A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.
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            Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN

            Eileen Morgan, Melina Arnold, A Gini … (2023)
            Objective Colorectal cancer (CRC) is the third most common cancer worldwide. The geographical and temporal burden of this cancer provides insights into risk factor prevalence and progress in cancer control strategies. We examine the current and future burden of CRC in 185 countries in 2020 and 2040. Methods Data on CRC cases and deaths were extracted from the GLOBOCAN database for the year 2020. Age-standardised incidence and mortality rates were calculated by sex, country, world region and Human Development Index (HDI) for 185 countries. Age-specific rates were also estimated. The predicted number of cases and deaths in 2040 were calculated based on global demographic projections by HDI. Results Over 1.9 million new CRC cases and 930 000 deaths were estimated in 2020. Incidence rates were highest in Australia/ New Zealand and European regions (40.6 per 100 000, males) and lowest in several African regions and Southern Asia (4.4 per 100 000, females). Similar patterns were observed for mortality rates, with the highest observed in Eastern Europe (20.2 per 100 000, males) and the lowest in Southern Asia (2.5 per 100 000, females). The burden of CRC is projected to increase to 3.2 million new cases and 1.6 million deaths by 2040 with most cases predicted to occur in high or very high HDI countries. Conclusions CRC is a highly frequent cancer worldwide, and largely preventable through changes in modifiable risk factors, alongside the detection and removal of precancerous lesions. With increasing rates in transitioning countries and younger adults, there is a pressing need to better understand and act on findings to avert future cases and deaths from the disease.
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              Cytokine Profile and Disease Severity in Patients with COVID-19

              Ali Ghazavi, Ali Ganji, Nafiseh Keshavarzian … (2020)
              Highlights • Patients with COVID-19 show a prominent Th1 and Th17 cytokine profile. • COVID-19 induces the expression of TGF-β. • TGF-β can be used as a predictive factor of disease severity in patients with COVID-19.
              Article 0 comments Cited 86 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jun-Feng Wang
                Xiao-Xia Yang
                Jian Zhang
                Yan Zheng
                Fu-Qing Zhang
                Xiao-Feng Shi
                Yu-Liang Wang
                Journal
                Journal ID (nlm-ta): World J Gastrointest Oncol
                Journal ID (publisher-id): WJGO
                Title: World Journal of Gastrointestinal Oncology
                Publisher: Baishideng Publishing Group Inc
                ISSN (Electronic): 1948-5204
                Publication date (Print): 15 May 2024
                Publication date (Electronic): 15 May 2024
                Volume: 16
                Issue: 5
                Pages: 2113-2122
                Affiliations
                Department of Colorectal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
                Department of Neurology, Tianjin First Center Hospital, Tianjin 300192, China
                Prosthodontics Studio, Tianjin Stomatological Hospital, Tianjin 300041, China
                Department of Clinical Laboratory Medicine, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
                Department of Clinical Laboratory Medicine, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
                Department of Emergency, Tianjin First Central Hospital, Tianjin 300192, China
                Department of Clinical Laboratory Medicine, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China. wang_yu_l@ 123456163.com
                Author notes

                Co-first authors: Jun-Feng Wang and Xiao-Xia Yang.

                Co-corresponding authors: Xiao-Feng Shi and Yu-Liang Wang.

                Author contributions: Wang JF, Yang XX, Zhang J, Zheng Y, and Wang YL performed the experiments; Wang JF, Yang XX, and Wang YL acquired and analyzed the data; Wang JF, Shi XF, and Wang YL interpreted the data; All authors approved the final version of the article. Wang YL and Shi XF conceived and designed the project and have played pivotal and indispensable roles in the experimental design, data interpretation, and manuscript preparation as co-corresponding authors; Zhang FQ drafted the manuscript; Wang YL wrote the manuscript, conceptualized, designed, and supervised the entire project process; conducted the literature research, revised the manuscript, and handled its submission; Shi XF made significant contributions by conducting data re-analysis and re-interpretation.

                Supported by National Natural Science Foundation of China, No. 81470982.

                Corresponding author: Yu-Liang Wang, MD, PhD, Director, Department of Clinical Laboratory Medicine, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, No. 22 Pingjiang Road, Hexi Distinct, Tianjin 300211, China. wang_yu_l@ 123456163.com

                Article
                Other ID: jWJGO.v16.i5.pg2113 Publisher-manuscript ID: 91680
                DOI: 10.4251/wjgo.v16.i5.2113
                PMC ID: 11099452
                PubMed ID: 38764823
                SO-VID: eb64b492-33b5-4052-808b-9d6f4f44db3f
                Copyright © ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
                License:

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                Date received : 2 January 2024
                Date revision received : 19 January 2024
                Date accepted : 7 March 2024
                Categories
                Subject: Basic Study

                Keywords: colorectal cancer,covid-19,adipose-derived mesenchymal stem cells,t helper cell,immunomodulation
                Data availability:
                Keywords: colorectal cancer, covid-19, adipose-derived mesenchymal stem cells, t helper cell, immunomodulation

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