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

Abstract

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).

Efficacy of mesenchymal stromal cells and cellular products in improvement of symptoms for COVID‐19 and similar lung diseases

“…Additionally, evidence showed that MSC-based treatments could inhibit collagen accumulation and alveolar collapse (Chen, Yu, et al, 2020).…”

“…Therefore, it was suggested that in the absence of inflammatory responses, MSCs have the potential to manage severe symptoms of COVID‐19 infection in patients and reduce lung injury (Rao et al, 2020; Taghavi‐Farahabadi et al, 2020). Latterly Wilson et al showed that treatment of (nine) patients with ARDS by allogeneic MSC does not cause pre‐specified adverse effects, such as cardiac arrhythmia, hypoxemia, and ventricular tachycardia (Chen, Yu, et al, 2020; Wilson et al, 2015).…”

“…Micro‐vesicle transferring of MSCs improve macrophage phagocytosis capacity (Taghavi‐Farahabadi et al, 2020). Additionally, evidence showed that MSC‐based treatments could inhibit collagen accumulation and alveolar collapse (Chen, Yu, et al, 2020).…”

“…The potential of source, painless noninvasive procedure, low immunogenicity, high proliferation capacity and free of ethical concerns make menstrual‐blood derived MSCs a suitable choice (Chen, Qu & Cheng, Chen, et al, 2019; Chen, Qu, & Xiang, 2019; Chen, Yu, et al, 2020; Khoury et al, 2014; Tang et al, 2020). Chen used Men‐MSCs for H7N9‐induced ARDS.…”

Therapeutic Potential of Autologous Adipose Derived Mesenchymal Stem Cells in Human POI and Ovarian Aging

“…This condition has a prevalence of 1 out of 100 women before the age of 40; and in 1 out of 1000 under 30, and the risk variation depends on race, which ranges from 0.1% in Japanese to 1% in Caucasians, and 1.4% in Africans and Hispanics [5,6,7]. Several POI etiopathogeneses have been described; i.e., autoimmune diseases [8], oxidative stress [9], genetical predisposition [10], radiotherapy and chemotherapy in the treatment of cancer [11,12,13]. All of these may cause problems in the collection and maintenance of primordial follicles in addition to follicular atresia and apoptosis of granulosa cells [14,15,16,17].…”