ABSTRACT
The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people's life health. Two current studies have indicated a favorable role for mesenchymal stem/stromal cells (MSCs) in clinical remission of COVID-19 associated pulmonary diseases, yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction. In the present review, we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury, acute respiratory distress syndrome, and pulmonary fibrosis. Furthermore, we review the underlying mechanism of MSCs including direct- and trans-differentiation, autocrine and paracrine anti-inflammatory effects, homing, and neovascularization, as well as constitutive microenvironment. Finally, we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice. Collectively, this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.
ABSTRACT
Owing to the boundedness of conventional remedies upon articular cartilage for self-rehabilitation and the incrementally senior citizens, the incidence of osteoarthritis (OA) is increasing worldwide. Empirical studies have revealed the advantageous and promising potentials of mesenchymal stem/stromal cells (MSCs) on the refractory OA, whereas the deficiency of systematic and detailed exploration of MSC-based therapy largely hampers the large-scale applications in regenerative medicine. Herein, we initially utilized the monosodium iodoacetate- (MIA-) induced OA rabbit models and investigated the therapeutic effect of human umbilical cord-derived UC-MSCs at serial dose gradients with the splendid hyaluronic acid and/or propylene glycol hydrogels (HA, HA/PG), respectively. Afterwards, we turned to a dual-luciferase reporter tracing system and evaluated the spatiotemporal distribution and metabolokinetics of bifluorescence expressing UC-MSCs (BF-MSCs) in OA rats. Of the aforementioned trials, we verified that the combination of HA/PG and middle-dose MSCs (0.5×107 cells/ml) eventually manifested the optimal efficacy on OA rabbits. Furthermore, with the aid of the bioluminescence imaging (BLI) technology for dynamic in vitro and in vivo tracking, we intuitively delineated the spatiotemporal distribution and therapeutic process of BF-MSCs in OA rats, which substantially confirmed the reinforcement of HA/PG on BF-MSCs for OA treatment. Collectively, our data conformably demonstrated that the middle dose of UC-MSCs combined with HA/PG hydrogel was sufficient for optimal MSC-based formulation for blocking OA progression and promoting cartilage repair, which supplied overwhelming new references and enlightened MSC-based therapeutic strategies for cartilage defects.
ABSTRACT
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since Dec 2019, known as COVID-19 or 19-nCoV, has led to a major concern of the potential for not only an epidemic but a pandemic in China and now it seems to be a public health problem all over the world. The general mortality rate of the COVID-19 was about 3%. However, the mortality risk seems to be a significant increase in elderly and cases with chronic disease, who are more likely to develop into acute respiratory distress syndrome (ARDS). There still lacks effective methods for ARDS of COVID-19 patients and the prognosis was poor. Mesenchymal Stem Cells (MSCs) based treatment has the advantage of targeting numerous pathophysiological components of ARDS by secreting a series of cell factors, exerting anti-inflammatory, antioxidative, immunomodulatory, antiapoptotic, and proangiogenic effects, resulting in significant structural and functional recovery following ARDS in various preclinical models. Recently, pilot clinical studies indicated MSCs based therapy was promise in treatment of ARDS caused by SARS-CoV-2. However, little is known about MSCs therapy for ARDS caused by COVID-19.