2008 May;15(10):711-5. doi: 10.1038/gt.2008.35. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. CAS  This result provided an important rationale for a precision medicine approach for MSC treatment [48]. 2017;377:562–72. Lancet. 2020. https://doi.org/10.1093/cvr/cvaa106. Taghavi-farahabadi M, Mahmoudi M, Soudi S, et al. PubMed Central  Brain-derived neurotrophic factor (BDNF)-gene transduction further enhanced the protective efficacy against the ischemic damage. Transplantation of Mesenchymal Stem Cells Improves Amyloid-β Pathology by Modifying Microglial Function and Suppressing Oxidative Stress. Stem Cell Res Ther 11, 305 (2020). MSCs can release VEGF and HGF, which work together to stabilize endothelial barrier function by restoring pulmonary capillary permeability. Correspondence to : Table S1. The safety and possible efficacy have been demonstrated in some ARDS patients. Mehta P, McAuley DF, Brown M, et al. L. Danielyan, S. Beer-Hammer, A. Stolzing et al., “Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer’s and Parkinson’s disease,” Cell Transplantation, vol. MSCs are investigational products that have been studied extensively for broad clinical applications in … Since the last 15 years, an increasing number of preclinical and clinical studies (>500) have been registered [5] using hMSCs as a valuable source in treatment of chronic diseases (e.g., autoimmune such as RA, inflammatory such as T1D, and CVD or degenerative diseases such as ALS, PD, and AD). Since SARS-CoV-2 mainly affects the lungs [41], the distribution of MSCs in the peripheral blood is mainly concentrated in the lungs after intravenous infusion [42], indicating that MSCs are a promising treatment option for patients with COVID-19 pneumonia. EV, extracellular vesicles; NETs, neutrophil extracellular traps; Treg, regulatory T cells; AT-II, alveolar type II; ROS, reactive oxygen species; FGF7, fibroblast growth factor 7; Ang-1, angiopoietin-1. Managing the potential and pitfalls during clinical translation of emerging stem cell therapies. HHS Rojas M, Xu J, Woods CR, et al. CAS  Blood. Based on this result, Zhang and colleagues further studied the rationale for why the MSC-administered group exhibited an increased 28-day mortality (not significant). Matthay MA, Calfee CS, Zhuo H, et al. PubMed  Cookies policy. Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells. 2019;72(3):867-884. doi: 10.3233/JAD-190817. Gene-modification of MSC with therapeutic cytokines clearly augmented the antitumor effect and prolonged the survival of tumor-bearing animals. Although refined research techniques have been applied, the effectiveness of MSC engraftment is still not satisfactory. There was no difference in the 28-day mortality between the MSC group and the placebo group. LincRNA-p21 promotes mesenchymal stem cell migration capacity and survival through hypoxic preconditioning. 2018;132:57–80. MSC treatment is protective in a mouse model with reduced concentrations of IL-6 and fibronectin and increased levels of TAC, while MSCs worsened injury in the opposite conditions. Wilson JG, Liu KD, Zhuo H, et al. Teuwen LA, Geldhof V, Pasut A, et al. Pittenger M, Mackay A, Beck S, et al. 2015;3:24–32. The serum SP-D level in the MSC group on the 5th day was significantly lower than that on day 0 (p = 0.027), and the IL-8 level was not significantly changed. Hoffmann M, Kleine-Weber H, Schroeder S, et al. Because MSCs have obvious therapeutic effects, such as promoting the repair of epithelial and endothelial tissues, clearance of alveolar fluid and microorganisms, and anti-inflammatory and antiapoptotic effects, MSC-based cell therapy is a promising strategy for the treatment of ARDS. Khoury M, Cuenca J, Cruz FF, et al. Huang D, Ren J, Li R, Guan C, Feng Z, Bao B, Wang W, Zhou C. Stem Cell Rev Rep. 2020 Feb;16(1):41-55. doi: 10.1007/s12015-019-09940-0. Shyamsundar M, McAuley DF, Ingram RJ, et al. The possible mechanism is shown in Fig. MSC transplantation protected the brain tissue from acute ischemic damage in the midcerebral artery occlusion (MCAO) animal model. Eventually, transplantation of MSCs into myocardial infarction animal model along with fibronectin-immobilized PCL nanofibers was very successful [15]. Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis. The promise of mesenchymal stem cell therapy for acute respiratory distress syndrome. In a follow-up study, Simonson et al. Gene therapy employing MSC as a tissue-protecting and targeting cytoreagent would be a promising approach. N Engl J Med. This site needs JavaScript to work properly. COVID-19: consider cytokine storm syndromes and immunosuppression. Article  Prevention of LPS induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. Copyright © 2018 Farid Menaa et al. https://doi.org/10.1016/S2213-2600(14)70217-6. Chillà A, Margheri F, Biagioni A, Del Rosso T, Fibbi G, Del Rosso M, Laurenzana A. Subsequently, SARS-CoV-2 enters the host cell through phagocytosis, thereby partially reducing or completely abrogating the enzymatic function of ACE2 and increasing the concentration of proinflammatory angiotensin II. As a result, MSC administration within the first few hours of SS may increase the short-term survival of patients with neutropenia but cannot prevent death from sepsis-related organ dysfunction over time [44]. J Trauma Acute Care Surg. ARDS is a severe acute respiratory failure syndrome with a high mortality rate. MSCs improved gas exchange and reduced the levels of BALF chemokines and cytokines, including GM-CSF, MIG, IL-1α, IFN-γ, IL-6, and TNF-α [26]. Respir Res. Khatri M, Richardson LA, Meulia T. Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model. In 2015, Wilson et al. MSCs release the peptide LL37 and inhibit neutrophil intravasation and NET formation, favoring bacterial clearance. 2020. https://doi.org/10.1038/s41591-020-0868-6. MSCs activate regulatory T cells by inhibiting proliferation and activation. Severe adverse events in three patients were subsequently noted several weeks after infusion but were thought to occur before MSC injection based on the MRI results. Epub 2019 Jul 9. Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. However, to the best of our knowledge, there are still no approved medicines for ARDS; thus, the development of effective treatment strategies or agents is highly desired. Guzik TJ, Mohiddin SA, Dimarco A, et al. Gene Ther. Springer Nature.  |  Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells. Stem Cell Res Ther. 2005 Jan;11(1):96-104. doi: 10.1016/j.ymthe.2004.09.020. California Privacy Statement, https://doi.org/10.1165/rcmb.2004-0330OC. https://doi.org/10.1016/j.isci.2019.05.004. Cytokine storms are the main cause of ARDS in COVID-19 patients [34]. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Another study found that after infection with COVID-19, MSC treatment inhibited the overactivation of the immune system and promoted endogenous repair by improving the lung microenvironment. Mei SH, McCarter SD, Deng Y, et al. 2020;23:E71–83. 123–139, 2014. Manage cookies/Do not sell my data we use in the preference centre. Most of the positive blood cultures from patients were gram-negative. 1. Interleukin-1β causes acute lung injury via αvβ5 and αvβ6 integrin-dependent mechanisms. Cell-Mediated Release of Nanoparticles as a Preferential Option for Future Treatment of Melanoma. 1999;284:143–7. Schematic diagram of the mechanisms of action of MSCs in ARDS. NIH Keratinocyte growth factor promotes epithelial survival and resolution in a human model of lung injury. Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. At the same time, a variety of lung and systemic inflammatory markers, including epithelial cell apoptosis, leakage of alveolar-capillary fluid, proinflammatory cytokines, microRNAs, and chemokines, also declined. Get the latest public health information from CDC: https://www.coronavirus.gov. The results of the Russian clinical trial of mesenchymal stromal cells (MSCs) in severe neutropenic patients (pts) with septic shock (SS) (RUMCESS trial). 2020 Jul 2;12(7):1771. doi: 10.3390/cancers12071771. Extracellular vesicles, including exosomes, have shown strong abilities to repair, regenerate, and protect against various organ injuries [15, 16], which may play important roles in the treatment of ARDS. Stem Cell Res Ther. 2020. https://doi.org/10.1101/2020.02.17.20024166. The virus-induced production of proinflammatory cytokines, including TNF-α and CXCL-10, was inhibited after MSC treatment [27]. Acute respiratory distress syndrome. Lancet Respir Med. Mesenchymal stem cells (MSCs) have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. Review articles are excluded from this waiver policy.

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