LitCovid-sentences  

PMC:7264098 / 1882-27686 JSONTXT 13 Projects

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Id Subject Object Predicate Lexical cue
T11 0-54 Sentence denotes Understanding Coronaviruses and Their Impact on Health
T12 55-308 Sentence denotes A new strain of coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2, as named by the International Committee on Taxonomy of Viruses) discovered in Wuhan, China, in December 2019, has caused a global disruption and COVID-19 pandemic.
T13 309-353 Sentence denotes SARS-CoV-2 is classified as Betacoronavirus.
T14 354-441 Sentence denotes In general, coronavirus is the name of viruses that belong to the family Coronaviridae.
T15 442-484 Sentence denotes These are classified into four categories:
T16 485-559 Sentence denotes Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus.
T17 560-720 Sentence denotes Alpha- and betacoronaviruses infect mammals, gammacoronaviruses infect avian species, and deltacoronaviruses infect both mammalian and avian species (Li, 2016).
T18 721-924 Sentence denotes Coronaviruses are typically spherical, fatty enveloped viruses, which encapsulate large single-stranded RNA genomes, notably, the largest genome among all RNA viruses, typically ranging from 27 to 32 kb.
T19 925-1048 Sentence denotes The genome is packed inside a helical capsid formed by the nucleocapsid protein (N) and further surrounded by the envelope.
T20 1049-1275 Sentence denotes Graphical Abstract Mesenchymal stem cells and their secreted extracellular vesicles are capable of abrogating inflammation and inducing lung regeneration, which can improve recovery of the patients hospitalized with COVID-19.
T21 1276-1368 Sentence denotes Coronaviruses have characteristic clove-shape spikes (“corona”) protruding from the surface.
T22 1369-1535 Sentence denotes The spikes are protein complexes that virus uses to bind to a receptor (receptor-binding subunit S1) and mediate entry into host cells (a membrane-fusion subunit S2).
T23 1536-1664 Sentence denotes Upon binding virus fuses with the human cell membrane, allowing the genome of the virus to enter the cell and begin replication.
T24 1665-1859 Sentence denotes The receptor-binding domain of SARS-CoV-2 spikes are closely related to those of SARS-CoVs (73.8–74.9% amino acid identity) and SARS-like CoVs (75.9–76.9% amino acid identity) (Wu et al., 2020).
T25 1860-2033 Sentence denotes SARS-CoV-2 uses the human angiotensin I converting enzyme 2 (ACE2) receptor for cell entry (Lu et al., 2020), which could potentially facilitate human-to-human transmission.
T26 2034-2192 Sentence denotes In addition to mediating virus entry, the spike feature is a critical determinant of viral host range and tissue tropism and a cause of host immune responses.
T27 2193-2389 Sentence denotes Since the ACE2 receptor is widely distributed on the human alveolar type II cells and capillary endothelium (Hamming et al., 2004), lungs are particularly susceptible to the SARV-CoV-2 infections.
T28 2390-2593 Sentence denotes Indeed, recent studies demonstrated that the disease could affect a large portion of the lungs causing widespread damage (Figure 1), which subsequently may lead to permanent changes to the lung function.
T29 2594-2802 Sentence denotes Recent MRI study of a 59-year old male patient diagnosed with COVID-19 showed that the disease is not confined to any particular area, but that it can spread across the entire lungs (Figure 1; Mortman, 2020).
T30 2803-2942 Sentence denotes However, this is not caused directly by the virus, but rather the host immune response leading to overwhelming cytokine storm in the lungs.
T31 2943-3239 Sentence denotes The overexpression of cytokines such as IL-2, IL-6, IL-7, GSCF, IP10, MCP1, MIP1A, and TNFα is followed by edema, which impairs oxygen exchange, and may lead to acute respiratory distress syndrome (ARDS) causing potential acute cardiac injury, secondary infection (Huang et al., 2020), and death.
T32 3240-3398 Sentence denotes Figure 1 Widespread distribution of the areas affected by COVID-19 and the effects of stem cells and extracellular vesicles on the recovery of lung function.
T33 3399-3564 Sentence denotes Most recent observations suggest that the devastating complication of COVID-19 may not be a typical pneumonia or ARDS, but rather a dysfunction in blood oxygenation.
T34 3565-3703 Sentence denotes This statement is supported by the fact that over 80% of COVID-19 patients placed on ventilators in New York City have died (Baker, 2020).
T35 3704-3914 Sentence denotes According to Dr. Cameron Kyle-Sidell (Maimonides Medical Center, New York, March 31, 2020), COVID-19 patients show symptoms associated with high altitude without adaptation response (Gattinoni et al., 2020a,b).
T36 3915-4183 Sentence denotes Clinically these cases resemble more closely high-altitude sickness characterized by decompression pulmonary sickness or high-altitude pulmonary edema (HAPE) with distinctive features of severe hypoxemia often associated with near normal respiratory system compliance.
T37 4184-4383 Sentence denotes Since cytokines and inflammation play dominant role in the development of COVID-19-induced lung damage, immunological therapies capable of attenuating cytokine storm may be the key treatment options.
T38 4384-4542 Sentence denotes However, traditional immunomodulatory capacity of common immunotherapeutics are targeted at one or two factors, which may not induce a strong enough response.
T39 4543-4703 Sentence denotes Mesenchymal stem/stromal cells (MSCs) have demonstrated potent and broad immunomodulatory and anti-inflammatory capacity (Abdi et al., 2008; Wada et al., 2013).
T40 4704-4790 Sentence denotes Therefore, MSC-based therapy could potentially be an effective treatment for COVID-19.
T41 4791-4963 Sentence denotes Notably, due to their regenerative properties (Mahla, 2016), MSCs can promote the repair of damaged tissue, in order to prevent long-term lung damage inflicted by COVID-19.
T42 4964-5257 Sentence denotes Importantly, MSCs have been shown to stabilize endothelial fluid leakage and maintain alveolar-capillary barrier function, which is vital to sustain or decrease lung permeability due to inflammation, thus attenuating the development of interstitial lung edema (Bhattacharya and Matthay, 2013).
T43 5259-5307 Sentence denotes Are We All Affected the Same Way by Coronavirus?
T44 5308-5555 Sentence denotes Coronavirus-related infections can cause a variety of illnesses, which range from asymptomatic or mild such as a common cold, to severe including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now, COVID-19.
T45 5556-5660 Sentence denotes The severity of these infections also varies widely between age-groups and different ethnic populations.
T46 5661-5786 Sentence denotes Older people are at increased risk of acquiring the infection and are likely to develop severe symptoms culminating in death.
T47 5787-6077 Sentence denotes Interestingly, there appears to also be gender disparity in the number of acquired cases of COVID-19 with higher percentage of men (~60%) than women being infected, as was first reported in China (Li et al., 2020); other countries have also reported higher case fatality rate (CFR) in men1.
T48 6078-6245 Sentence denotes Similar observations were reported in a meta-analysis in relation to the MERS-CoV, where the number of infected men was double that of females (Badawi and Ryoo, 2016).
T49 6246-6390 Sentence denotes Epidemiological studies tracing SARS-CoV showed that SARS-CoV was also more prevalent in men and associated with increased CFR (Karlberg, 2004).
T50 6391-6775 Sentence denotes A number of proposed explanations for these gender differences in terms of both the incidence and CFR of MERS-CoV, SARS-CoV, and now COVID-19 infections, include past smoking history, work-environmental factors, different treatment regimens, and underlying biological differences such as gender-specific innate and adaptive immune responses (Karlberg, 2004; Klein and Flanagan, 2016).
T51 6776-7072 Sentence denotes Clear biological differences between male and female gender include the presence of different steroid hormones and two instead of one X-chromosomes in females, which influences the number of immune response X-linked genes and genetic susceptibility to viral infections (Klein and Flanagan, 2016).
T52 7073-7380 Sentence denotes Notably, experiments in mice, which seem to represent responses in humans well in this particular study, demonstrated greater susceptibility of male mice to enhanced viral titres, vascular leakage, and alveolar edema, compared to age-matched female mice infected with SARS-CoV (Channappanavar et al., 2017).
T53 7381-7530 Sentence denotes This was attributed to differential immune cells and inflammatory responses including inflammatory monocyte macrophages, neutrophils, T- and B-cells.
T54 7531-7675 Sentence denotes Notably, in this pre-clinical study, sex-dependent differences in susceptibility to SARS-CoV infection became more prominent with advancing age.
T55 7676-7907 Sentence denotes In fact, once female mice underwent ovariectomy or were administered estrogen receptor antagonist treatment, the mortality associated with SARS-CoV infection increased, suggesting a protective effect of estrogen receptor signaling.
T56 7908-8132 Sentence denotes Although experimental and mechanistic data is lacking in relation to the novel COVID-19 sex-specific differences, it is likely that similar factors and biological differences will be applicable as with MERS-CoV and SARS-CoV.
T57 8133-8335 Sentence denotes It is important for these differences to be clearly elucidated particularly in the context of the treatment response, with certain treatments potentially being more effective in a specific gender group.
T58 8336-8483 Sentence denotes Nevertheless, other confounding factors need to be taken into the account such as age, smoking, comorbidities and work-environmental circumstances.
T59 8485-8523 Sentence denotes Current Treatments Are Palliative Only
T60 8524-8776 Sentence denotes Despite over 300 active and recruiting clinical trials and a number of trials already completed, there is still no robust evidence that any of the investigated therapeutics are effective as treatments for COVID-19 disease (Channappanavar et al., 2017).
T61 8777-8871 Sentence denotes Equally, there is no evidence to support prophylactic treatment either (Sanders et al., 2020).
T62 8872-8982 Sentence denotes However, there are only 29 trials in adult patients with placebo-controlled arm (Channappanavar et al., 2017).
T63 8983-9126 Sentence denotes Various types of pharmacological treatments are currently under investigation including anti-viral, anti-malarial and anti-inflammatory agents.
T64 9127-9316 Sentence denotes These therapies generally target the following processes: (1) the entry of the virus into host cells, (2) multiplication of the viral genetic material, and (3) immune response/inflammation.
T65 9317-9550 Sentence denotes Most of these agents have been previously used as treatments for SARS-CoV and MERS-CoV, however the overall conclusions of the meta-analyses published in 2006 and 2018, respectively, did not support the use of any particular regimen.
T66 9551-9733 Sentence denotes In relation to the meta-analysis of SARS-CoV treatments, the authors systematically reviewed 54 treatment studies, 15 in vitro studies and three ARDS studies (Stockman et al., 2006).
T67 9734-9943 Sentence denotes Although the combination of ribavirin and interferon-based (IFN) treatments appears the most effective for MERS (Morra et al., 2018), this needs to be confirmed in randomized placebo-controlled trial settings.
T68 9944-10213 Sentence denotes In terms of vaccines, there are at least 115 vaccine candidates in development with a number of these already initiated in human trials, however we expect vaccines to be available to people under emergency use only in early 2021 (Callaway, 2020; Thanh Le et al., 2020).
T69 10214-10406 Sentence denotes Overall, there are a number of concerns in relation to the design of various trials and interpretation of the data investigating different pharmacological agents for the treatment of COVID-19.
T70 10407-10674 Sentence denotes Some of these limitations include small cohort sizes, no placebo control arm, lack of considerations for gender, comorbidities, concurrent treatments, route of drug delivery, primary outcomes lacking effects on the viral load or suppression, and adverse drug effects.
T71 10675-10910 Sentence denotes Whilst most of these therapies represent supportive and symptomatic care, there are a number of adjunctive therapies such as corticosteroids, immunomodulatory, and immunoglobulin agents that have been investigated with limited results.
T72 10911-11236 Sentence denotes In particular, corticosteroids are not recommended for the management of COVID-19 because of the associated adverse effects, which potentially include increased viral load, secondary infections and complications, similarly to what was observed previously in influenza, SARS-CoV and MERS-CoV infections (Russell et al., 2020).
T73 11237-11525 Sentence denotes Potential benefits in severe COVID-19 cases are emerging with IL-6 monoclonal antibody, Tocilizumab, and the use of convalescent plasma or hyperimmune immunoglobulins, however better designs and further trials are needed for this to be established (Chen L. et al., 2020; Fu et al., 2020).
T74 11526-11802 Sentence denotes Nevertheless, none of these therapies are capable of lung tissue repair and regeneration, particularly in those patients with complications such as ARDS, which is why the use of stem cell-based therapies could be beneficial in COVID-19 patients with respiratory complications.
T75 11804-11849 Sentence denotes Are Stem Cells a Solution to COVID-19 Crisis?
T76 11850-11946 Sentence denotes MSCs could be the most promising candidate for the treatment of SARS-CoV-2 infections (Table 1).
T77 11947-12215 Sentence denotes Since the key for the treatment of SARS-CoV-2 infection lies in the management of the cytokine storm in the lungs, MSCs are well-suited considering their main mechanism of action is through their immunomodulatory and anti-inflammatory properties (Fatima et al., 2017).
T78 12216-12682 Sentence denotes The safety profile and efficacy of MSCs are well-established based on the results from a number of completed clinical studies investigating the therapeutic potential of these therapies in lung diseases such as ARDS (Matthay et al., 2019; Chen J. et al., 2020) and bronchopulmonary dysplasia (Namba, 2019), cardiovascular diseases (Kim et al., 2015; Suvakov et al., 2020), diabetes (Thakkar et al., 2015; Cho et al., 2018), and spinal cord injury (Xu and Yang, 2019).
T79 12683-12777 Sentence denotes Table 1 Selected clinical studies using stem cells for the treatment of SARS-CoV-2 infection.
T80 12778-12872 Sentence denotes Cell type Dosage Number of patients Outcome Stage of study Reference or NCT numbers#
T81 12873-13175 Sentence denotes MSCs (tissue source unspecified) Single dose of 1 × 106 cells per kg, IV 7 patients with severe COVID-19 pneumonia Regulation of inflammatory response (Decreased plasma C-reaction protein, reduced cytokine-secreting immune cells, reduced TNF-α, increased IL-10 and VEGF) Complete Leng et al., 2020
T82 13176-13263 Sentence denotes Adipose tissue-derived MSCs Two serial doses of 1.5 × 106 cells per kg, IV Estimated:
T83 13264-13323 Sentence denotes 100 patients N/A Phase 2; Not yet recruiting NCT04348461
T84 13324-13395 Sentence denotes Dental pulp stem cells 3 × 107 cells IV on day 1, 4, and 7 Estimated:
T85 13396-13461 Sentence denotes 20 patients N/A Phase 1 clinical trial; recruiting NCT04336254
T86 13462-13540 Sentence denotes Dental pulp stem cells 1 × 106 cells per kg IV on day 1, 3, and 7 Estimated:
T87 13541-13605 Sentence denotes 24 patients N/A Early Phase 1; Not yet recruiting NCT04302519
T88 13606-13704 Sentence denotes Wharton's Jelly MSCs 3 doses of 1 × 106 cells per kg IV, 3 days apart from each other Estimated:
T89 13705-13769 Sentence denotes 5 patients N/A Phase 1 clinical trial; recruiting NCT04313322
T90 13770-13851 Sentence denotes MSCs (tissue source unspecified) 3 × 107 cells IV on day 0, 3, and 6 Estimated:
T91 13852-13917 Sentence denotes 20 patients N/A Phase 1 clinical trial; recruiting NCT04252118
T92 13918-13991 Sentence denotes Umbilical cord MSCs 9.9 × 107 cells IV on day 1, 3, 5, and 7 Estimated:
T93 13992-14057 Sentence denotes 10 patients N/A Phase 2 clinical trial; recruiting NCT04269525
T94 14058-14150 Sentence denotes Umbilical cord MSCs 0.5 × 106 cells per kg body weight IV on day 1, 3, 5, and 7 Estimated:
T95 14151-14200 Sentence denotes 48 patients N/A Not yet recruiting NCT04273646
T96 14201-14270 Sentence denotes Bone Marrow MSCs Single dose of 1 × 106 cells per kg, IV Estimated:
T97 14271-14344 Sentence denotes 20 patients N/A Phase 1 clinical trial; Not yet recruiting NCT04346368
T98 14345-14495 Sentence denotes Human embryonic stem cells derived matrix-regulatory cells 3 cohorts who receive doses of 3, 5, or 10 million cells per kg body weight IV Estimated:
T99 14496-14560 Sentence denotes 9 patients N/A Phase 1 clinical trial; recruiting NCT04331613
T100 14561-14623 Sentence denotes # NCT numbers refer to ClinicalTrials.gov Identifier numbers.
T101 14624-14787 Sentence denotes Other types of stem cells investigated for potential treatment of SARS-CoV-2 infections include genetically engineered human induced pluripotent stem cells (iPSC).
T102 14788-14994 Sentence denotes A recent study presented a deleterious effect on the cells in vitro when iPSCs were exposed to SARS-CoV-2, where the pluripotency of iPSCs was lost leading to fibroblast-like phenotype (Zebin et al., 2020).
T103 14995-15115 Sentence denotes Therefore, evidence-based selection of stem cell type for the treatment of COVID-19 is critical for safety and efficacy.
T104 15117-15174 Sentence denotes Advancing Stem Cells to Mainstream Medicines for COVID-19
T105 15175-15427 Sentence denotes Currently, there are 17 clinical trials investigating the therapeutic potential of MSCs in COVID-19 patients that are registered on clinicaltrials.gov website; most of these trials are either recruiting patients or have not yet started the recruitment.
T106 15428-15646 Sentence denotes The vast majority of the trials are selecting patients with COVID-19 and pneumonia, and utilizing allogeneic bone-marrow or umbilical cord-derived MSCs transplanted intravenously on three different occasions (Table 1).
T107 15647-15710 Sentence denotes Approximately 50% of the trials are being carried out in China.
T108 15711-15972 Sentence denotes Three trials (NCT03042143 already recruiting in Northern Ireland, United Kingdom; NCT04333368 planned in France and NCT04345601 in the United States of America, not yet recruiting) aim to investigate the therapeutic potential of MSCs in SARS-CoV-2-induced ARDS.
T109 15973-16279 Sentence denotes MSCs have already been investigated in ARDS both in the pre-clinical (Curley et al., 2013) and clinical settings (Wilson et al., 2015), which demonstrated the ability of MSCs to promote distal lung epithelial repair, albeit potentially limited in the presence of hypercapnic acidosis (Fergie et al., 2019).
T110 16280-16506 Sentence denotes Whilst a number of MSC-related trials in COVID-19 patients with respiratory complications are underway, limited reports are available that these treatments have the potential to improve recovery and survival of these patients.
T111 16507-16907 Sentence denotes Some encouraging data is emerging, for example in a recent study, which assessed 7 patients transplanted with intravenous MSCs (1 × 106 per kg) and 3 patients in the placebo controlled group albeit consisting of all female patients, showed significant improvement in pulmonary function and symptoms as well as substantial reduction in inflammation compared to the placebo controlled group (Figure 2).
T112 16908-17000 Sentence denotes Figure 2 Outcomes of MSCs treatment for COVID-19 patients reported in pilot clinical trial:
T113 17001-17018 Sentence denotes ChiCTR2000029990.
T114 17019-17268 Sentence denotes Despite the lack of convincing evidence in support of MSC-based therapies for respiratory complications of COVID-19, a number of promising trials are currently underway, which could revolutionize the treatment prospects for severe COVID-19 patients.
T115 17269-17522 Sentence denotes Regardless of the urgency of the need for MSC-based therapies for COVID-19, it is critical that the production of MSCs is in compliance with good manufacturing practices (GMP) and follows strict regulations prior to being approved for the use in humans.
T116 17523-17673 Sentence denotes The use of unauthorized and unapproved stem cell therapies not validated through stringent multicenter clinical trials should be strongly discouraged.
T117 17674-17938 Sentence denotes At the same time current findings imply that there is a need for globally coordinated approach and support to conduct multicenter clinical trials to demonstrate safety and effectiveness of various types of stem cells to treat COVID-19-induced health complications.
T118 17939-18138 Sentence denotes It also suggests that there is a need in biomedical research and development to establish the most effective stem cell types that are ideally suited for the treatment of aforementioned complications.
T119 18139-18428 Sentence denotes These developments will also require (a) GMP compliant technologies to mass produce stem cells, and (b) testing platforms that mimic human pathophysiology (e.g., 3D bioprinted organoids, organ-on-chip) to allow high-throughput screening and rapid testing of stem cells safety and efficacy.
T120 18429-18532 Sentence denotes Extracellular vesicles (EVs) are emerging as an attractive alternative to the whole cell–based therapy.
T121 18533-18746 Sentence denotes EVs have several advantages compared to the whole cell therapy including lower risk of tumorigenic effects, lower susceptibility to damage by hostile disease microenvironment and possibility for long-term storage.
T122 18747-18929 Sentence denotes The long-term storage is fundamental to make the treatment accessible in developing countries and it circumvents the need to have expensive GMP cell manufacturing facilities on-site.
T123 18930-19173 Sentence denotes Nevertheless, production of EVs must follow the same strict guidelines that apply to stem cells and any EV-based therapy needs to be approved by the governing bodies after being tested in clinical trials to demonstrate the safety and efficacy.
T124 19175-19211 Sentence denotes Factors Affecting the Quality of MSC
T125 19212-19362 Sentence denotes The successful translation of MSC-based therapies into the clinic for treatment of COVID-19-induced lung injuries is dependent on a number of factors.
T126 19363-19550 Sentence denotes In addition to desirable therapeutic effects, it is also important to understand the mechanism of action and the influence of various in vivo environments on the integrity of these cells.
T127 19551-19867 Sentence denotes Stem cells can be environmentally preconditioned by certain stimuli such as hypoxia or ischemia, which can induce certain signaling pathways to improve engraftment, survival, and function of transplanted cells in harsh environments within the injured lung (Sart et al., 2014; Kim et al., 2015; Saparov et al., 2016).
T128 19868-20119 Sentence denotes Other methods of preconditioning stem cells include the formation of three-dimensional stem cell aggregates that lead to enhanced extracellular matrix secretion, anti-inflammatory properties and cell survival (Bartosh et al., 2010; Sart et al., 2014).
T129 20120-20270 Sentence denotes Pre-treatment of MSCs with various pharmacological factors can, in fact, improve therapeutic effects and tissue repair capabilities (Hu and Li, 2018).
T130 20271-20532 Sentence denotes Furthermore, bioengineering approaches such as the use of bioreactors can overcome the limitations of a large scale production of stem cells necessary for transplantation and maintenance of the stemness during and after delivery to patients (Madl et al., 2018).
T131 20533-20684 Sentence denotes Therefore, these technologies can accelerate the transition from bench to bedside without compromising the quality of the stem cells reaching patients.
T132 20685-20850 Sentence denotes For example, tuneable materials can be used as an artificial niche to expand or differentiate stem cells to mature cell types (Yang et al., 2014; Madl et al., 2017).
T133 20851-21064 Sentence denotes Materials such as hydrogels used as carriers for stem cells can also lead to enhanced regenerative response by regulating fate and activity of transplanted stem cells (Engler et al., 2006; Chaudhuri et al., 2016).
T134 21065-21237 Sentence denotes These approaches are currently less widely used for pulmonary applications compared to other target organs and thus future investigations will lead to innovative solutions.
T135 21239-21297 Sentence denotes Is the Treatment Efficacy Dependent on the Delivery Route?
T136 21298-21439 Sentence denotes In the majority of clinical trials investigating the treatment of SARS-CoV-2 infections so far, MSCs are delivered via the intravenous route.
T137 21440-21583 Sentence denotes Since intravenous route does not specifically target lungs, the inhalation route that delivers cells directly to lungs could be more effective.
T138 21584-21720 Sentence denotes However, uniform delivery of cells to lungs through inhalation is technically challenging (Kim et al., 2016; Kim and Chrzanowski, 2019).
T139 21721-21969 Sentence denotes Strong evidence is emerging to suggest that the therapeutic potential of MSCs is attributed mostly to their secreted EVs via paracrine effects, and MSCs could also be referred to as medicinal signaling cells (Bjørge et al., 2018; Kim et al., 2019).
T140 21970-22085 Sentence denotes Delivery of EVs to lungs is feasible and exogenous EVs can facilitate prompt activity directly at the injured site.
T141 22086-22270 Sentence denotes There is a pilot clinical study that intends to deliver MSC-derived exosomes via the inhalation route to patients with severe pneumonia arising from SARS-CoV-2 infection (NCT04276987).
T142 22271-22491 Sentence denotes In this clinical trial, the main advantage of administering MSC-derived exosomes via inhalation route compared to the intravenous administration is the prevention of their aggregation within the injured microcirculation.
T143 22492-22737 Sentence denotes In addition, MSC-derived exosomes have other advantages over MSCs including lower or no risk of mutagenicity and oncogenicity as well as the storage stability of several weeks or months facilitating less urgent transportation and administration.
T144 22738-22930 Sentence denotes A recent study using animal models of pulmonary fibrosis also demonstrated therapeutic potential of inhaled lung spheroid cell-secretome and exosomes for lung regeneration (Dinh et al., 2020).
T145 22931-23176 Sentence denotes While the intravenous route is the most widely used often for the ease of administration albeit invasive, the route of cell delivery should be tailored according to the disease in question and patient's circumstances (Kim and Chrzanowski, 2019).
T146 23177-23431 Sentence denotes As evident from a number of clinically available inhaled medications for chronic lung disease, the inhalation route of delivering therapeutics to the lungs is a more direct route with lower incidence of adverse effects, compared to the intravenous route.
T147 23432-23573 Sentence denotes Nevertheless, the environment in the hospital has to be appropriately managed for inhaled administration of a treatment in COVID-19 patients.
T148 23574-23779 Sentence denotes A number of studies have demonstrated the feasibility of delivering stem cells via spray for direct pulmonary delivery with high viability (Kardia et al., 2016; Kim et al., 2016; Skolasinski et al., 2020).
T149 23780-23963 Sentence denotes Inhalation route of stem cell administration is an opportunity for efficient delivery of stem cells directly to the lungs, yet it remains an under-explored research area in the field.
T150 23965-24056 Sentence denotes The Future of Stem Cells for the Treatment of SARS-CoV-2 and Other Coronaviruses Infections
T151 24057-24312 Sentence denotes Although only a limited number of MSC-based clinical trials have been completed to date, in a small number of COVID-19 patients, the prospects of using these cells in the clinical setting to treat and prevent COVID-19-induced lung damage appear promising.
T152 24313-24522 Sentence denotes Successfully completed Phase I trials for the treatment of ARDS and emerging promising preliminary results from current trials will soon shed light on the effectiveness of MSCs for the treatment of SARS-CoV-2.
T153 24523-24690 Sentence denotes The proposed clinical study that aims to deliver MSC-derived exosomes via the inhalation route to COVID-19 patients (NCT04276987) will potentially be a paradigm shift.
T154 24691-25003 Sentence denotes In the light of a recent study that demonstrated efficacy of inhaled stem cell-derived therapy in both ex vivo and animal models of pulmonary fibrosis (Dinh et al., 2020), the inhalation route due to advantages outlined above, may become more routinely investigated along with the conventional intravenous route.
T155 25004-25263 Sentence denotes Importantly, regardless of the route of delivery and type of stem cells, larger-scale clinical trials strictly designed with the placebo arm and patient randomization are necessary to achieve successful stem cell-based therapies for the treatment of COVID-19.
T156 25265-25292 Sentence denotes Data Availability Statement
T157 25293-25460 Sentence denotes The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.
T158 25462-25482 Sentence denotes Author Contributions
T159 25483-25609 Sentence denotes All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
T160 25611-25631 Sentence denotes Conflict of Interest
T161 25632-25804 Sentence denotes The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.