Muse cell known as a kind of Stem cell enabled therapy for SARS-CoV-2-Lung and Olfactory Impairment in Syrian Hamsters and may also have therapeutic effects for long COVID

Background Long COVID, including symptoms such as asthma, allergies, musculoskeletal pain, diabetes, insomnia, headaches, chronic fatigue, and frailty persisting for at least 2 months following acute SARS-CoV-2 infection, is a global health concern with no established treatments. While some studies demonstrated efficacy using mesenchymal stem cells (MSCs), outcomes have been inconsistent. Methods In the present study, we evaluated a small, distinct subset of SSEA-3(+) MSCs, known as multilineage-differentiating stress-enduring (Muse) cells, in a preclinical model of SARS-CoV-2 infection. Here, in a Syrian hamster model of SARS-CoV-2 infection, Syrian hamsters were intranasally inoculated with SARS-CoV-2 on day 0, and then on day 2, the hamsters were intravenously administered Muse cells, non-Muse cells, or vehicle (saline). On day 8, the hamsters were sacrificed, and the lungs and olfactory bulb (OB) were removed from the body to perform the experiments including inflammatory response, apoptosis, fibrosis (lung only). At the same time, total RNA was extracted from the lung and OB for RNA-seq and IPA analysis. Results We demonstrated that intravenous treatment with human-bone marrow-derived Muse cells more effectively reduced inflammation, fibrosis, and apoptosis than non-Muse-MSCs while preserving oxygen saturation, body weight, lung and olfactory bulb structure, and alveolar air space. RNA sequencing identified 64 differentially expressed genes associated with Muse cell-mediated tissue protection, with distinct profiles in olfactory bulb and lung tissues. Although this study does not directly assess long COVID, the marked suppression of severe COVID-associated pathology suggests that Muse cell treatment holds promise as a potential therapeutic approach for long COVID. Conclusions Our findings demonstrated that Muse cells suppressed the expression of inflammatory, apoptosis, fibrosis mediators that may exacerbate severe COVID-19 pathology as ARDS. Some reports suggest that SARS-CoV-2 infection in the olfactory bulb provides a route for SARS-CoV-2 viral invasion of the brain, leading to neurologic symptoms of long COVID. Therefore, we propose that Muse cells could ameliorate both pulmonary and neurologic components of long COVID by suppressing key inflammatory and fibrotic pathways. Because Finally, these findings suggest that Muse cells may be a promising therapeutic approach for mitigating the symptoms of severe COVID-19 infection and preventing long COVID.