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Writing and reviewing of the paper by TH and MS was supported by the grant "EVA4.0", No. CZ.02.1.01/0.0/0.0/16_019/0000803 financed by OP RDE. ML was supported by the project "SURE--SUstaining and Enhancing REsilience of European Forests" financed by the German Federal Ministry of Food and Agriculture. CMH was supported by a grant overseen by the French National Research Agency (ANR) as part of the "Investissements d'Avenir" program (ANR-11-LABX-0002-01, Lab of Excellence ARBRE). MJS was supported by project Innovative forest MAnagEment STrategies for a Resilient biOeconomy under climate change and disturbances (I-MAESTRO; ForestValue Eranet, FNR project ID 2219NR189).

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.

Pluripotency reprogramming and transdifferentiation induced by transcription factors can generate induced pluripotent stem cells, adult stem cells or specialized cells. However, the induction efficiency and the reintroduction of exogenous genes limit their translation into clinical applications. Small molecules that target signaling pathways, epigenetic modifications, or metabolic processes can regulate cell development, cell fate, and function. In the recent decade, small molecules have been widely used in reprogramming and transdifferentiation fields, which can promote the induction efficiency, replace exogenous genes, or even induce cell fate conversion alone. Small molecules are expected as novel approaches to generate new cells from somatic cells in vitro and in vivo. Here, we will discuss the recent progress, new insights, and future challenges about the use of small molecules in cell fate conversion.

These results indicate that STAT3, but not MAPK, can critically regulate photoreceptor development during mouse retina development.